Methods. SCID-HuRAg mice were treated separately with CD147/HAb18 mAb, anti-TNF- mAb or a combination of both. The mice in control group were treated with anti-Japanese encephalitis virus mAb. The volume of engrafts was measured and the number of inflammatory cells and cartilage erosion score were examined. Expression of MMP-2, -3 and -9 was determined by immunohistochemistry. Human inflammatory cytokine levels in mouse sera were assessed using cytometric bead array kit.

Results. The volume of engrafts decreased significantly in SCID-HuRAg mice treated separately with anti-CD147 mAb or anti-TNF- mAb, and in the mice treated with anti-CD147 mAb plus anti-TNF- mAb (P < 0.05). Significant reduction was observed in cartilage erosion score in anti-CD147 treatment group and combined treatment group (P < 0.05). Immunohistochemical analysis showed that expression of MMP-2, -3 and -9 was lower in the anti-CD147 treatment group and combined treatment group than in the control mAb group (P < 0.05). Moreover, the level of TNF-, IL-6 and -8 in CD147 mAb group showed a significant decrease compared with that of the control mAb group (P < 0.05).

Conclusions. CD147/HAb18 mAb can reduce cartilage erosion and synovitis by inhibition of the MMPs and reduction of inflammatory cytokines in SCID-HuRAg mice, which suggests that CD147/HAb18 mAb is a promising treatment option for RA patients.

Methods. FURA-2 microfluorimetry was used to measure agonist-evoked changes of [Ca²⁺]_i in isolated mouse and human salivary acinar cells following exposure to NO donors.

Results. NO had a biphasic effect on salivary acinar function. Acute exposure to NO (2 min) caused a cyclic guanosine monophosphate (GMP)-dependent, 1-H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-sensitive increase in the Ca²⁺ signal elicited in response to acetylcholine (ACh) stimulation, consistent with stimulation of ryanodine receptors by cyclic adenosine diphosphate ribose. Prolonged exposure to NO (>40 min) significantly reduced the ACh-evoked Ca²⁺ signal by a mechanism independent of cyclic GMP. We found no differences between the responses of human and mouse acinar cells.

Conclusion. Our data show that chronic exposure to NO, which is known to be elevated in SS, could have a role in salivary gland hypofunction. We note a similarity in the response to stimulation of salivary acinar exposed to NO and that which we have previously reported in salivary acinar cells isolated from patients with SS. We speculate that NO-mediated nitrosylation of one or more elements of the signal transduction pathway could underlie down-regulation of salivary function in SS.

Methods. The expression of JAM-B, JAM-C, CD99, ICAM-1 and VCAM-1 in SSc skin was determined by immunohistology and cell surface ELISA. Myeloid U937 cell–SSc dermal fibroblast adhesion assays or in situ adhesion assays to SSc skin were performed.

Results. JAM-C and CD99 expression on endothelial cells (ECs) in SSc skin was decreased compared with expression on normal ECs. CD99 was overexpressed on mononuclear cells in SSc skin and on SSc dermal fibroblasts. Neutralizing ICAM-1 inhibited the binding of U937 cells to SSc dermal fibroblasts. In addition, blocking both ICAM-1 and VCAM-1 inhibited U937 cell adhesion to either proximal (less involved) or distal (more involved) SSc skin.

Conclusions. These studies show that JAM-C and CD99 are aberrantly expressed in SSc skin. However, these adhesion molecules do not mediate myeloid cell–SSc skin adhesion. In contrast, we demonstrate an important role for ICAM-1 and VCAM-1 in the retention of myeloid cells in SSc skin, suggesting that targeting these molecules may be useful SSc therapies.

Methods. Synoviocytes isolated from RA patients were stimulated with recombinant SAA and cellular supernatants were analysed by CCL20-specific ELISA. CCL-20 mRNA expression was analysed by RT–PCR.

Results. SAA is a most potent inducer of CCL20 secretion in RA synoviocytes compared with other inflammatory cytokines (IL-1β, TNF- and IL-17A). SAA stimulation induced CCL20 mRNA expression in RA synoviocytes, which was not affected by polymyxin B pre-treatment. SAA-induced CCL20 production was down-regulated by NF-B inhibition and partially by c-jun N-terminal kinase (JNK) inhibition. SAA-induced CCL20 production was also suppressed by dexamethasone or FK506.

Conclusion. These findings suggest that SAA may be implicated in the recruitment of lymphocytes, including CCR6-expressing Th17 cells, in RA synovium by up-regulating CCL20 production in synoviocytes.

Methods. Sera from 28 AS patients, 28 HLA-B27+ healthy relatives, 28 unrelated healthy subjects and 14 RA patients were included. Salmonella typhimurium proteins were electrophoretically separated and blotted onto nitrocellulose sheets for immunodetection with sera from AS patients and unrelated healthy subjects. The electroeluted 30-kDa band (p30) and a crude lysat (StCL) from S. typhimurium were used as antigen to evaluate the IgM, IgA and IgG (total and subclasses) antibody levels by ELISA. An inhibition assay was carried out to confirm the specificity of IgG response to the p30.

Results. Twenty out of 28 AS patients (71.4%) and 4 out of 28 unrelated healthy subjects (14.3%) recognized a 30-kDa band from S. typhimurium with IgG antibodies. Six out of 28 AS patients (21.4%) and 4 out of 28 unrelated healthy subjects (14.3%) detected it with IgA antibodies. Recognition of p30 and StCL by both IgA and IgG antibodies was higher in AS patients than in control groups (P = 0.003, <0.001 and 0.003 for IgA and <0.001, 0.003 and 0.006 for IgG). Sera from AS patients have higher percentage of IgG antibodies p30 and IgG3 subclass was higher in AS patients than in control groups. No differences in the IgM response were found.

Conclusions. Data presented suggest the association between the p30 and AS.

Methods. We quantified messenger RNA (mRNA) expression of FOXP3, a critical regulator for the development and function of Tregs, in the urinary sediment of 25 subjects with active lupus nephritis (LN), 17 with inactive lupus and 7 healthy subjects.

Results. We found that the expression level of FOXP3 was significantly higher in urine from patients with active LN than from subjects with inactive lupus and healthy controls (24.5 ± 45.8 vs 0.8 ± 1.0 vs 0.6 ± 0.8 copy; P < 0.001). In the active group, urinary FOXP3 mRNA expression level was higher in patients with proliferative LN than non-proliferative nephritis (34.6 ± 56.3 vs 2.7 ± 2.1 copy; P = 0.019). Urinary FOXP3 mRNA level significantly correlated with SLEDAI (r = 0.668; P < 0.001) and proteinuria (r = 0.414; P = 0.006). In the active group, urinary FOXP3 mRNA level also significantly correlated with histological activity index (r = 0.541; P = 0.009) and marginally with intra-renal FOXP3 mRNA level (r = 0.360; P = 0.08). Urinary FOXP3 mRNA in patients with no response to therapy was higher than those with partial response or complete response (57.6 ± 69.8 vs 2.4 ± 1.9 copies; P = 0.02).

Conclusion. We concluded that urinary FOXP3 mRNA is markedly up-regulated in patients with active LN, and the level of expression is closely correlated with the clinical and histological disease activity. A high urinary FOXP3 mRNA in LN predicts a poor therapeutic response. Measurement of FOXP3 mRNA in urine sediment may be a non-invasive biomarker for assessing the severity and risk stratification in LN.

Methods. Since 2000, we have followed 296 patients with SpA [198 AS, 21 SpA associated with IBD (9 ulcerative colitis, 12 Crohn's disease) and 77 psoriatic arthritis] treated with at least one anti-TNF drug (infliximab, etanercept or adalimumab), and 112 SpA patients treated only with conventional DMARDs who served as controls. Considering the cumulative time of exposure to each anti-TNF agent, the frequencies of new-onset PAEs in exposed patients were calculated.

Results. Respective cumulative exposure times were 287, 290 and 62 patient-years for infliximab, etanercept and adalimumab. We observed the following PAEs: five psoriasis (three under infliximab and one with etanercept or adalimumab), three AAU (1/100 patient-years, all under etanercept) and four IBD (three under etanercept and one under infliximab). There was no significant association among any of these PAEs and a specific anti-TNF agent; nor significant difference in the overall PAEs among patients receiving anti-TNF drugs or controls (P = 0.303), the latter experiencing two psoriasis and three AAU.

Conclusions. Undesirable side effects—IBD, AAU and psoriasis—may appear with anti-TNF drugs. Even if they are, a priori, paradoxical, no evidence supports any PAEs to be anti-TNF agent-specific in SpA.

Methods. A group of practicing UK rheumatologists formulated contemporary management principles and clinical practice recommendations concerning both diagnosis and treatment. Areas of clinical uncertainty were documented, leading to research recommendations.

Results. A fundamental concept governing treatment of RA is minimization of cumulative inflammation, referred to as the inflammation–time area under the curve (AUC). To achieve this, four core principles of management were identified: (i) detect and refer patients early, even if the diagnosis is uncertain: patients should be referred at the first suspicion of persistent inflammatory polyarthritis and rheumatology departments should provide rapid access to a diagnostic and prognostic service; (ii) treat RA immediately: optimizing outcomes with conventional DMARDs and biologics requires that effective treatment be started early—ideally within 3 months of symptom onset; (iii) tight control of inflammation in RA improves outcome: frequent assessments and an objective protocol should be used to make treatment changes that maintain low-disease activity/remission at an agreed target; (iv) consider the risk–benefit ratio and tailor treatment to each patient: differing patient, disease and drug characteristics require long-term monitoring of risks and benefits with adaptations of treatments to suit individual circumstances.

Conclusion. These principles focus on effective control of the inflammatory process in RA, but optimal uptake may require changes in service provision to accommodate appropriate care pathways.

Methods. One hundred and fifty men or women aged 50–75 years suffering from KOA were randomized to one of five IA therapies: (i) clodronate 0.5 mg one IA injection/week for 4 weeks; (ii) clodronate 1 mg one IA injection/week for 4 weeks; (iii) clodronate 2 mg one IA injection/week for 4 weeks; (iv) clodronate 1 mg two IA injections/week for 2 weeks (clodronate 1 + 1 mg); and (v) HA 20 mg one IA injection/week for 4 weeks.

Results. Visual analogue scores (VASs) for different types of pain and the Lequesne index significantly improved in all treatment groups after the first injection and continued to improve even 2–4 weeks after the last injection without significant difference among the groups. A significant (P = 0.03) linear trend for a dose–response (0.5–2 mg clodronate) relationship was found for active movement VAS pain. Both joint extension and mobility scores improved significantly at all time points in all treatment groups without statistical differences among them.

Conclusions. This study indicates that IA clodronate provides symptomatic and functional improvements at least as good as those obtained with HA.

Trial Registration. Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali - Agenzia Italiana del Farmaco. Comitato Etico Azienda Ospedaliera Universitaria Senese number CLIO 22/02 http://oss-sper-clin.agenziafarmaco.it

Methods. Fifty-six patients with pSLE, divided into three groups (pre-pubertal, peripubertal and post-pubertal onset), were studied. The SDI (SLICC/ACR Damage Index for SLE), patients’ characteristics, disease manifestations and treatments were compared using Fisher's exact test and Kruskal–Wallis test. Kaplan–Meier curves were constructed to compare the risk of damage occurrence.

Results. The risk of damage (SDI >=1) significantly decreased when age at disease onset increased (89% in pre-pubertal pSLE, 57% in peripubertal pSLE and 38% in post-pubertal pSLE). This excess of risk was found in all disease duration intervals studied (1–3, 3–5, 5–8, 8–10, >10 years) and at the end of follow-up. Kaplan–Meier curves indicated a higher and earlier risk of damage in younger patients. Young children showed higher frequency of autoimmune family history. The frequency of neuropsychiatric disorders and damages decreased with age at disease onset (P < 0.05). Cumulative duration of high-dose prednisone (> 0.5 mg/kg/day) and number of immunosuppressive drugs used that seem to contribute to damage significantly increased when age at disease onset decreased.

Conclusions. The risk of damage is inversely correlated with age at disease onset in pSLE. The poorer outcome observed in younger children may be explained by a more severe disease expression, may be a higher infectious susceptibility, and a more aggressive therapy, particularly within the first 6 months of disease course.

Methods. Eighty-eight post-menopausal RA patients were randomized to receive vitamin D3 and calcium supplementation with or without HRT (oestradiol plus noretisterone acetate). The levels of total sRAGE in sera were measured before, 1 and 2 years after treatment initiation. Potential associations between sRAGE levels, bone/cartilage metabolic markers and BMD were investigated.

Results. Patients receiving HRT displayed significantly decreased levels of serum sRAGE at 1 and 2 years as compared with levels at study entry. The increase in serum oestradiol was associated with the decline in sRAGE levels. Importantly, sRAGE levels at baseline significantly correlated with bone/cartilage turnover markers including C-terminal propeptide of type I procollagen, carboxyterminal telopeptide of type I collagen and cartilage oligomeric matrix protein, and the decrease of sRAGE levels paralleled with diminished concentration of these molecules. BMD in hip and femoral neck and progression of Larsen score at 1 year were associated with baseline sRAGE levels. The decline in sRAGE levels significantly correlated with an increase in total BMD following 2 years of treatment in patients receiving HRT but not in the control group.

Conclusion. Our findings suggest that HRT decreases the levels of endogenous sRAGE in post-menopausal RA patients implicating its role in sRAGE regulation. In addition, serum sRAGE was associated with BMD and markers of bone/cartilage metabolism. These data suggest that sRAGE is involved directly or indirectly in bone metabolism.

Trial registration. Current Controlled Trials, ISRCTN46523456, http://www.controlled-trials.com/isrctn/search.html?srch=ISRCTN46523456

Methods. Using MEDLINE, EMBASE and AMED, 20 randomized controlled trials (RCTs) were found and divided into nine treatment subcategories: acupuncture (n = 2 trials), anti-oxidants (n = 2), biofeedback (n = 5), essential fatty acids (n = 3), Ginkgo biloba (n = 1), l-arginine (n = 2), laser (n = 3), glucosaminoglycans (n = 1) and therapeutic gloves (n = 1). Trials in each subcategory were meta-analysed together.

Results. Several categories did not have enough trials to do a meta-analysis and most trials were negative, of poor quality and done prior to 1990. Biofeedback was negative for a change in frequency, duration and severity of RP attacks, and actually favoured control (sham biofeedback; P < 0.02). The therapeutic glove favoured active treatment (P < 0.00001). Laser resulted in one less RP attack on average over 2 weeks vs sham [weighted mean difference (WMD) 1.18; 95% CI 1.06, 1.29], and a change in severity of attacks (WMD 1.98; 95% CI 1.57, 2.39; P < 0.05). No significant differences were found in the nutritional supplements that were studied.

Conclusions. There is a need for well-designed trials of CAM in RP. The literature is inconclusive except that biofeedback does not work for RP, therapeutic gloves may improve RP (but results may not be generalizable due to single trial site and no intent-to-treat analysis) and laser may be effective but the improvement may not be clinically relevant.

Methods. Fourteen patients with primary SS (pSS) were included (Group A). All patients were anti-Ro and/or -La antibody positive except one. Patients were treated with HCQ for a period of up to 6 months. Glandular function was determined by Saxon's and Schirmer's tests for the dominant eye at baseline and at the end of the treatment. We included a control group of 21 patients with objective sicca symptoms and positive -fodrin antibodies (Group B).

Results. In patients with pSS (Group A), a significant increase in saliva production after HCQ treatment (P = 0.022) was observed. A subanalysis revealed that particularly the -fodrin-positive patients responded to HCQ (P = 0.017 -fodrin positive vs P = 0.4 -fodrin negative). Interestingly, patients with sicca symptoms and -fodrin antibodies (Group B) showed a significant increase in tear production (P = 0.001). In addition, there was a positive correlation between the -fodrin IgA antibody concentration and the Schirmer's test at baseline (r = 0.66; P = 0.001) and after treatment (r = 0.6; P = 0.004) in this group.

Conclusions. HCQ treatment led to a beneficial effect on xerostomia in patients with pSS who lack severe organ manifestations. The response was greater in -fodrin-positive patients.

Methods. Sixty-three female SSc patients (diffuse/limited: 49/14), all having pulmonary high-resolution CT (HRCT) scans, taken previously for evaluating lung involvement were included. At the time of the scans, mean age and disease duration of the patients were 50.1 ± 8.5 and 10.2 ± 7.8 years, respectively. As the control group, 45 age-matched female patients, having normal pulmonary HRCT scans taken previously for evaluating non-specific symptoms, were included.

Results. Frequency of incomplete thymus involution was significantly higher in SSc patients (12/63; 19%) compared with the control group (2/45; 4.4%; P = 0.022). In SSc patients with pulmonary fibrosis, incomplete thymus involution was significantly lower (3/38; 7.9%) than those without pulmonary fibrosis (9/25; 36%; P = 0.007).

Conclusion. The present study shows significantly higher frequency of radiological incomplete thymus involution in SSc compared with normal controls. Furthermore, less common occurrence of pulmonary fibrosis in SSc patients with incomplete thymus involution deserves attention. These findings may have some implications regarding the possible role of thymic abnormalities at least in some patients with SSc.

Methods. From a population of hyperuricaemic veterans of [serum urate level >416 µmol/l (7.0 mg/dl)] at least 40 years of age, we compared the risk of death between incident allopurinol users (n = 2483) and non-users (n = 7441). We estimated the multivariate mortality hazard ratio (HR) of allopurinol use with Cox proportional hazards models.

Results. Of the 9924 veterans (males, 98% and mean age 62.7 years), 1021 died during the follow-up. Patients who began treatment with allopurinol had worse prognostic factors for mortality, including higher BMI and comorbidities. After adjusting for baseline urate levels, allopurinol treatment was associated with a lower risk of all-cause mortality (HR 0.78; 95% CI 0.67, 0.91). Further adjustment with other prognostic factors did not appreciably alter this estimate (HR 0.77; 95% CI 0.65, 0.91). The mean change from baseline in serum urate within the allopurinol group was –111 µmol/l (–1.86 mg/dl). Adjusting for baseline urate level, allopurinol users had a 40 µmol/l (0.68 mg/dl) lower follow-up serum urate value than controls (95% CI –0.55, –0.81).

Conclusion. Our findings indicate that allopurinol treatment may provide a survival benefit among patients with hyperuricaemia.

Methods. MEDLINE, EMBASE and CINAHL databases were searched for RCTs of glucocorticoids in RA. RCTs fulfilling the following criteria were included: double-blinded, placebo-controlled, lasted 1 year or longer, used prednisolone (or equivalent) and in English. Toxicity was assessed by number of the patients withdrawn for adverse events (AEs), and the numbers of serious adverse events (SAEs) and AEs. RCTs were compared by meta-analysis using odd ratios (OR) with 95% CIs.

Results. Six RCTs with total of 689 patients met the inclusion criteria. All RCTs lasted >=2 years. All studies allowed concomitant use of NSAIDs and DMARDs. Toxicity of glucocorticoid therapy based on number of patients withdrawn was limited (OR = 1.09; 95% CI 0.52, 2.25). Using number of AEs per patient-year (OR = 1.19; 95% CI 0.91, 1.57) and SAEs (OR = 1.06; 95% CI 0.67, 1.67) produced similar results. Efficacy/toxicity ratio was good for glucocorticoid therapy (number needed to harm/number needed to treat = 0.25).

Conclusion. Medium- to long-term glucocorticoid therapy in RA is associated with limited toxicity compared to placebo.

Methods. General practitioners used Calin's criteria for IBP to refer patients younger than 45 years to our early SpA clinic. We obtained the patients’ medical history and performed a clinical examination including plain X-rays and magnetic resonance images of all affected areas. Laboratory tests for acute-phase reactants and HLA-B27 were also obtained. Two rheumatologists made a diagnosis of SpA according to the existing criteria.

Results. Of the 92 patients referred, 30 (33%) were diagnosed with SpA and 62 (67%) with a non-inflammatory disorder. Spontaneous awakening night pain, the presence of Calin's criteria for IBP and tenderness of the SI joints (SIJs) were independently associated with SpA. Neck pain and reduced cervical spine sagittal movement occurred mostly with non-inflammatory disease. A history of night pain and improvement of pain with exercise but not with rest, as well as expression of HLA-B27 and abnormal CRP levels were significantly more common in patients with SpA.

Conclusions. Specific clinical symptoms such as spontaneous awakening night pain, cervical pain and tenderness of the SIJs on clinical examination appear useful in screening younger patients with back pain for early SpA.

Methods. SLE LUMINA (LUpus in MInorities: NAture vs nurture) patients (n = 637), aged >=16 years, disease duration <=5 years at baseline (T0), of African–American, Hispanic and Caucasian ethnicity were studied. Atherosclerotic cardiovascular damage was defined by the following items of the SLICC Damage Index (SDI) cardiovascular domain: angina or coronary artery by pass surgery, myocardial infarction and/or congestive heart failure; factors associated with its occurrence were examined by univariable and multivariable regression analyses.

Results. Forty-three (6.8%) of 637 patients developed cardiovascular damage over a mean ± s.d. total disease duration of 6.6 ± 3.6 years. Nearly 90% of the patients were women with a mean ± s.d. age of 36.5 (12.6) years; all ethnic groups were represented. By multivariable analyses, after adjusting for the cardiovascular manifestations present, age [odds ratio (OR) = 1.06; 95% CI 1.03, 1.09], male gender (OR = 3.57; 95% CI 1.35, 9.09) SDI at baseline (OR = 1.28; 95% CI 1.09, 1.50) and CRP levels [highest tertile (OR = 2.63; 95% CI 1.17, 5.91)] were associated with the occurrence of cardiovascular damage, whereas the number of years of education was negatively associated with such outcome (OR = 0.85; 95% CI 0.74, 0.94).

Conclusions. Our data suggest that atherosclerotic cardiovascular damage in SLE is multifactorial; traditional (age, gender) and disease-related factors (CRP levels, SDI at baseline) appear to be important contributors to such an occurrence. Tight control of the inflammatory process must be achieved to prevent it.

Methods. Members of the Vasculitis Clinical Research Consortium and European Vasculitis Study Group were given a list of 129 items of damage related to WG and microscopic polyangiitis (MPA). Participants were asked to rate each item of damage on an integer scale from 0 to 10, where 10 represented the most severe form of damage and 0 indicated ‘no impact’.

Results. A multidisciplinary panel of 50 investigators from North America, Europe and Australia–New Zealand participated. The highest median ratings (8–10) were assigned to items of damage associated with malignancy, tissue ischaemia, the central nervous system and cardiopulmonary manifestations. The mean scores ranged from 1.3 to 9.5. The highest s.d.s (>=2.5) were associated with forms of damage that may benefit from surgical intervention or may not be causally associated with WG or MPA. Lower scores were assigned by nephrologists in comparison with rheumatologists and by Americans in comparison to Europeans, although the difference in median ranks used by these groups was not statistically significant (P > 0.05 for the comparisons).

Conclusions. This exercise represents an important step in the development of a weighting system that may increase the utility of damage index scores for the assessment of patients with vasculitis.

Methods. A systematic literature search was performed to identify RCTs that compared the MTX–SSZ combination to either drug alone. The databases MEDLINE and the Cochrane Clinical Trials registry were searched from 1966 up to April 2007. The efficacy of the single therapeutic agents or their combination was assessed using the mean change in the disease activity score (DAS) and the ACR improvement criteria.

Results. Four RCTs were identified to compare the efficacy of the combination MTX–SSZ to the efficacy of either drug alone. Two parallel trials were performed with patients naïve to both drugs and two add-on trials were performed in SSZ failures. In the trials with naïve patients, the mean DAS changes for the combination MTX and SSZ pointed to a sub-additive efficacy. In the trials with patients who previously failed to SSZ, the mean DAS changes for the combination MTX and SSZ indicated additive efficacy.

Conclusions. In RA, addition of MTX to SSZ is a therapeutic option in SSZ failures, whereas combination of MTX and SSZ in DMARD-naïve patients has no added value.

Methods. The study involved 25 ERA patients (female/male 21/4; mean age 52.04 ± 14.05 years; disease duration <=12 months) and 25 healthy volunteers with no history or current signs of CAD or other traditional risk factors. Dipyridamole trans-thoracic stress echocardiography was preformed to evaluate CFR, and carotid ultrasound to measure the IMT of the common carotid arteries. Blood samples were obtained in order to assess ADMA levels before the patients had received any biological or non-biological DMARDs, or steroid therapy.

Results. CFR was significantly reduced in the ERA patients (2.5 ± 0.5 vs 3.5 ± 0.8; P <0.01). In particular, 6/25 (24%) had a CFR of <2 consistent with potentially dangerous coronary flow impairment. Common carotid IMT was significantly greater in the ERA patients, although still within the normal range (0.68 ± 0.1 vs 0.56 ± 0.11 mm; P <0.01). There was a significant correlation between CFR and plasma ADMA levels in the ERA population (r = –0.53; P <0.01). IMT was negatively associated with CFR (P <0.05).

Conclusions. Plasma ADMA levels were significantly higher in the ERA patients. A statistically significant negative effect of ADMA levels on CFR value was observed. The effect of ADMA levels on IMT is not significant.

Method. A retrospective chart review of patients referred to us for recurrent fevers. Genetic testing: systematic screening of exons 2 and 10 was performed in the MEFV gene. A subset of patients was also investigated for other auto-inflammatory genes.

Results. We analysed 94 patients (sex ratio:1). Forty-two percent of them were Jews and 17% were Arabs. The median age of onset was 2 years (3 months–47 years). Fever was >39°C in 80% of them, while the duration and frequency of an attack varied (<24 h: 8%; 1–3 days: 56%; >3 days: 36%; >2 months: 15%; 1–2 months: 48%; and <1 month: 37%, respectively). Peritonitis occurred in 97%, pleuritis in 25%, arthralgia in 53%; skin rashes in 20%, aphthosis in 18% and lymphadenopathy in 9%. MEFV mutations were M694V (60%) and M694I (7%). The R92Q TRAPS mutation was retrieved in 3/21 patients tested and the V377I MKD mutation in 1/6. Associated diseases in these patients were periodic fever, aphthosis pharyngitis and adenitis syndrome (4), AS (5), Crohn's disease (2) and Castleman's disease (1).

Conclusion. The clinical picture of French heterozygote patients with recurrent fevers resembles that of homozygote patients. Most of them required colchicine treatment.

Methods. Assessment of cardiovascular autonomic function was done in 20 lupus and 20 JIA patients, aged 8–16 years, by five non-invasive autonomic function tests (AFTs) and serum levels of neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP), as indicators of sympathetic and parasympathetic functions, respectively, in comparison with 40 matched healthy control subjects.

Results. Clinical evidence of CAN was found in 65 and 40% of lupus and JIA patients, respectively, and in none of healthy controls. Lupus and JIA patients had significantly lower serum NPY and VIP than controls (P < 0.001). The five AFTs score had significant negative correlations to NPY and VIP (P < 0.001). Patients with CAN had significantly lower serum NPY and VIP than patients without (P < 0.001). Clinical evidence of CAN was found in 41.7 and 14.3% of asymptomatic lupus and JIA patients, respectively. There was significant positive association between CAN and important disease manifestations, including activity, in these patients.

Conclusions. CAN is common in lupus and JIA patients, even in absence of relevant symptoms. Thus, assessments of cardiac autonomic function, by AFTs and serum autonomic neuropeptides (NPY and VIP), and the therapeutic effects of NPY and VIP are recommended in these patients.

Methods. The diagnosis of SSS was confirmed by clinical and histopathological examination. Collagen type 1 alpha-2 chain (Col1A2), fibronectin-1, thrombospondin-1, TGF-β, connective tissue growth factor (CTGF), IL-6, -1β, ET-1, Fibroblast growth factor receptor 3 (FGFR-3) and MCP-1 expression was analysed in SSS and age- and sex-matched healthy control skin by real-time PCR. VEGF expression was also studied.

Results. Histopathological examination showed flattened dermal papillae, a scarce presence of sub-epidermal microvessels and mild dermal fibrosis, but no inflammatory infiltrates. In the SSS dermis, the expression of IL-1β, -6 and MCP-1 was low, whereas VEGF was intensively expressed. No differences were observed for TGF-β, CTGF and ET-1. In contrast, col1A2, fibronectin-1 and thrombospondin-1 were overexpressed in the SSS dermis.

Conclusion. In our SSS patient, an overexpression of ECM proteins was detected, whereas no inflammatory infiltrates or up-regulation of pro-fibrotic cytokines were found. The data suggest that fibrosis in SSS might be independent from inflammation.

Methods. Our population was drawn from the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS), a prospective, observational cohort of RA patients. A total of 556 participants were genotyped using the Affymetrix 100K platform. Two hundred and sixty-two participants were on MTX therapy, including 120 on MTX monotherapy. The primary outcome was the disease activity score in 28 joints (DAS28-CRP). High disease activity was defined as DAS28-CRP >3.2. Low disease activity was defined as DAS28-CRP <=3.2. We studied three candidate alleles in the ATIC, ITPA and MTHFR genes for association with DAS28-CRP.

Results. Among participants on MTX monotherapy, those carrying the minor allele of ATIC SNP rs4673993 were more likely to have low disease activity (P = 0.01). None of the other SNPs was associated with disease activity. Among patients on any MTX (combination or monotherapy), the minor allele of ATIC rs4673993 was also associated with low disease activity (P = 0.04).

Conclusions. In this cross-sectional analysis, ATIC SNP rs4673993 was associated with low disease activity in patients on MTX. Further studies are needed to clarify the relationship between ATIC polymorphisms, disease activity and treatment response.

Methods. A case–control study (630 RA patients and 664 healthy blood donors, all white Spaniards) was performed with two single nucleotide polymorphisms (rs6920220 and rs10499194) situated at 6q23. Genotyping was performed by TaqMan technology; autoantibody-stratified analyses in RA patients were also undertaken to replicate the previously reported effect of these polymorphisms.

Results. No association was observed for rs10499194 even after autoantibody stratification. The minor allele frequency of rs6920220 was higher in anti-CCP or RF-positive patients than in controls (P = 0.014 and P = 0.015 respectively), thus replicating previous findings.

Conclusions. Our data replicate the association of rs6920220 with autoantibody-positive RA disease, although not for rs10499194.

Methods. Consecutive patients diagnosed with AAV at our centre, who were followed for at least 2 years, were included. The frequency of HLA antigens of AAV and WG patients was compared with 5872 healthy blood donors from the same region and with 4000 healthy Dutch controls originating from a Eurotransplant database.

Results. From 304 AAV patients, sufficient data were available. We found DR13(6) to be less prevalent and both DR4 and the ancestral haplotype A1B8DR3 more prevalent in patients with AAV compared with controls, particularly in patients with WG. In addition, DR1 was less prevalent in patients with WG in comparison with controls. Further, DR8 was more prevalent in patients with CSS compared with other forms of vasculitis and controls. There were no associations between HLA antigens and disease characteristics or course of AAV or WG.

Conclusions. AAV is associated with increased prevalence of DR4 and the ancestral haplotype A1B8DR3 and with decreased prevalence of DR13(6), particularly in patients with WG. In patients with WG, prevalence of DR1 was decreased, whereas in patients with CSS DR8 was increased. No associations between HLA antigens and disease characteristics or course of AAV were found.

Methods. Serum proteomic spectra were generated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with weak cationic exchange magnetic beads. A training set of spectra, derived from analysing sera from 32 patients with SLE, 43 patients with other autoimmune diseases and 43 age- and sex-matched healthy volunteers, was used to train and develop a decision tree model with a machine learning algorithm called decision boosting. A blinded testing set, including 32 patients with SLE, 42 patients with other autoimmune diseases and 40 healthy people, was used to determine the accuracy of the model.

Results. The diagnostic pattern with a panel of four potential protein biomarkers of mass-to-charge (m/z) ratio 4070.09, 7770.45, 28 045.1 and 3376.02 could accurately recognize 25 of 32 patients with SLE, 36 of 42 patients with other autoimmune diseases and 36 of 40 healthy people.

Conclusions. The preliminary data suggested a potential application of MALDI-TOF MS combined with magnetic beads as an effective technology to profile serum proteome, and with pattern analysis, a diagnostic model comprising four potential biomarkers was indicated to differentiate individuals with SLE from RA, SS, SSc and healthy controls rapidly and precisely.

Methods. A novel compound IF pattern, designated Scl-70 pattern, was characterized in routine ANA-HEp-2 IIF screening. Within the last 3 years, all serum samples presenting the Scl-70 pattern at the ANA-HEp2 IIF screening were tested for anti-topo I reactivity. Conversely, 16 serum samples with known anti-topo I reactivity and affinity-purified anti-topo I antibody preparations were tested for the Scl-70 pattern.

Results. The Scl-70 pattern comprised the staining of five cellular regions: nucleus, nucleolus and cytoplasm in interphase cells; nucleolar organizing region (NOR) and chromosomes in mitotic cells. All 81 serum samples selected as Scl-70 pattern reacted with topo I. All 16 anti-topo I samples and antibody preparations reproduced the Scl-70 pattern. This compound IF pattern was consistently observed in different commercial HEp-2 cell slides and in home-made slides with HEp-2 cells and human fibroblasts fixed with alternative protocols. Double IIF experiments demonstrated the co-localization of topo I and human upstream binding factor at the NOR.

Conclusions. The Scl-70 pattern belongs to the group of compound IF patterns that hold strong association with the respective autoantibody specificities, such as that observed with centromere protein F (CENP-F) and nuclear mitotic apparatus-1 (NuMA-1) protein. The identification of the Scl-70 pattern at routine ANA-HEp-2 IIF screening may lead to implementation of specific tests for the identification of anti-topo I antibodies. In addition, the Scl-70 pattern outlines cellular domains other than those previously reported for topo I, which is of interest for further understanding the roles of this enzyme in cell biology.

Methods. In this study, 119 patients with BD and 141 healthy controls were enrolled; every participant was a Korean. Nine single nucleotide polymorphisms previously detected in TLR4 by direct sequencing were analysed for an association with BD.

Results. The most frequent haplotype, TAGCGGTAA, was significantly increased in HLA-B*51-positive BD patients (49.5%), compared with healthy control participants [32.3%; P = 0.029; odds ratio (OR) = 2.01; 95% CI 1.25–3.23]. This haplotype was also significantly increased in BD patients with arthritis (48.2%; P = 0.003; OR = 1.96; 95% CI 1.26–3.26). There were no significant differences in the allele and genotype frequencies of patients and controls for each single nucleotide polymorphism.

Conclusions. The haplotype of TLR4 may increase the risk for developing BD and the complication of arthritis in the Korean population.

Methods. Heparinized bone marrow aspirate was obtained from patients with OA and RA. Mononuclear cells were cultured for 2 weeks and a colony-forming assay was performed. The phenotype of cells was analysed by flow cytometry. Passage 2 cells were cultured with β-glycerophosphate (bGP) in the control group and bGP, ascorbic acid and dexamethasone in the differentiation group. After 2 weeks, ALP staining and activity were performed. After 3 weeks, Alizarin Red S assay was performed. Total RNA was extracted from cells cultured for 2 and 3 weeks. Gene expression of bone formation factor was examined by real-time PCR.

Results. The phenotype of cells was identical in both OA and RA and the content was thought to be hMSCs. The results of ALP activity and Alizarin Red S assay showed higher levels in the differentiation group for both OA and RA samples compared with the control group. The results of a colony-forming assay were identical in both OA and RA samples. Gene expression in the differentiation group was higher than in the control group in both OA and RA samples. There was no significant difference between OA and RA samples in all experiments.

Conclusion. The function of osteoblastic differentiation of hMSCs is similar between OA and RA.

Methods. A three-stage population survey was conducted to identify individuals with RA using a health care access panel (18–79 years; n = 70 112). A 20-item postal screening questionnaire of musculoskeletal symptoms and diagnoses was followed by a detailed questionnaire for those who indicated the possibility of having RA. Respondents who fulfilled the modified ACR decision tree, who reported an RA diagnosis, care by a rheumatologist or the use of DMARDs were asked to participate in a clinical examination by rheumatologists who diagnosed the participants and rated the adequacy of treatment.

Results. RA could not be ruled out in 1177 cases, of which 643 agreed to participate in the clinical examination, which was finally attended by 317 participants. Attendees did not differ with regard to any health or treatment measure from those who did not attend. Forty-one RA patients were detected. Of them, 93% had seen a rheumatologist at least once and 63% within the last 12 months. A total of 73% had received DMARD therapy at some time and 59% were currently receiving it. An unmet need for DMARDs was discovered in 29% of the RA attendees. It pertained almost exclusively to the seronegative cases of which 29% had a need to start and 17% to increase a DMARD therapy according to the opinion of the examining rheumatologist.

Conclusion. Health care for RA patients has improved significantly since the last German RA survey in 1989. However, DMARD prescription still does not meet clinical recommendations, specifically in RF-negative patients. Since seronegative RA is a treatable disease, this group should not be overlooked.

Methods. A total of 100 patients with OA attending rheumatology clinics at a UK teaching hospital were randomly allocated to a CNS or JHD clinic and seen at 0, 16, 32 and 48 weeks. The study assessed (i) non-inferiority of the CNS with respect to clinical outcomes (pain, morning stiffness, self-efficacy, physical function and psychological status) and (ii) superiority of the CNS in terms of patient knowledge and satisfaction.

Results. Average pain at follow-up was lower in the CNS group: unadjusted mean difference for the JHD group minus the CNS group was 5.3 (95% CI –4.6, 15.2); adjusted was 1.6 (95% CI –5.7, 8.9). The corresponding effect size estimates were 0.20 (95% CI –0.17, 0.57) and 0.06 (95% CI –0.21, 0.33), respectively. There were similar outcomes in morning stiffness, physical function and self-efficacy. Patient knowledge and satisfaction were statistically significant at the 5% level attaining moderate to large effect sizes in favour of the CNS.

Conclusions. Our findings demonstrate that the clinical outcome of CNS care is not inferior to that of JHD care, and patients attending CNS gain additional benefit in that they are better informed about their disease and significantly more satisfied with care than are their counterparts.

Trial registration. ISRCTN 65487167.

Methods. Using relevant key words, we surveyed the websites of several scientific societies of immunology, paediatrics and rheumatology, as well as Pubmed and specialized databases for AIDs.

Results. The Internet provides a wide variety of information related to AIDs. Moreover, several other initiatives have been undertaken to create new resources for professionals. We reviewed six patient registries for rare AIDs, taking a special interest in the submission questionnaire. We revealed a wide overlap between the items used in the questionnaires, whereas the currently available registries appeared inappropriate for AIDs patients with complex or undefined diagnosis.

Conclusions. AIDs share common clinical features, pathophysiological pathways and therapeutic approaches. Although several resources are now available for rare AIDs, a unique and dedicated site gathering all aspects of these diseases as a whole is still lacking, i.e. covering research as well as the needs of AIDs patients and health care professionals. Our study thus advocates a merging of existing patient registries or the creation of a common database.

Methods. The cohorts were identified through a diagnostic index and were seen between January 1996 and December 2006. We identified 81 JLS patients to whom we age- and sex-matched 75 AD patients and 75 healthy controls. All patients were mailed a survey containing the English-language version of the German Revised Children's Quality of Life Questionnaire (KINDL) and the Children's Dermatology Life Quality Index (CDLQI). Linear regression models, adjusted for age and sex, examined differences in the KINDL and CDLQI scores.

Results. Survey completion rates in the JLS, AD and healthy control groups were 40, 28 and 44%, respectively. There was no difference in KINDL scores between JLS vs AD (73 vs 74, P = 0.3) and JLS vs healthy controls (73 vs 74, P = 0.8). However, CDLQI scores showed some impairment in HRQOL in JLS patients as compared with a healthy reference population, but not to the degree seen in AD (2 vs 4, P = 0.05). An exploratory analysis showed that HRQOL did not differ among the types of JLS with either measure.

Conclusion. JLS patients have some impairment in skin disease-specific HRQOL when compared with a healthy reference population, but not as severe as that seen in AD patients. Overall HRQOL in this JLS cohort was as good as healthy controls, a reassuring finding for patients, families and healthcare providers.

Methods. We analysed the clinical records of 232 patients with SLE who had at least 10 years of consistent follow-up at University College London Hospital (UCLH). We noted their SLICC/ACR Damage Index (SDI) scores and category of damage at 1 year post-diagnosis of SLE and every 5 years thereafter. For patients who had died, we determined the year and cause of death.

Results. Ninety per cent of patients had no damage at 1 year post-diagnosis of SLE; however by year 10, 50% had accrued some damage. Damage accrual was mostly in the neuropsychiatric, renal and musculoskeletal categories. An increase in damage score was associated with a higher risk of death overall. Forty-four patients died during the period of follow-up. Sepsis, cancer and organ failure (cardiac, renal and liver) were the main causes of death in this group of patients.

Conclusions. Damage accrual is associated with an increased risk of mortality. Infections remain an important cause of death in patients with SLE.

Methods. In a cross-sectional study, we determined the presence of anti-CCP and AKAs by ELISA and IIF, respectively, in a cohort of 90 consecutive patients with idiopathic inflammatory myopathy. Associations between anti-CCP and clinical manifestations or other autoantibodies were determined with the chi-square and Mann–Whitney U-tests. Radiographs of hands were retrospectively evaluated. Serum autoantibody profile was determined in all patients.

Results. Twelve patients were positive to anti-CCP (13.3%); in eight cases values were moderate–high. AKAs were not detected in any patient. Comparison between patients positive and negative to anti-CCP did not show clinical or biological differences. Arthritis joint erosions or positive status to anti-synthetase antibodies were not more frequent in patients with anti-CCP antibodies. Prevalence of RF was the only variable significantly associated with the presence of these antibodies (P = 0.043).

Conclusions. High titres of anti-CCP can occasionally be found in patients with inflammatory myopathy. Therefore, a possible diagnosis of RA should be considered with caution in these patients.

Methods. Thirty consecutive juvenile idiopathic arthritis (JIA) patients were included in this pilot study. Rheumatological and orthodontic examinations as well as US were performed within 1 month of the MRI in a blinded fashion. Joint effusion and/or increased contrast enhancement of synovium or bone were considered signs of active arthritis on MRI.

Results. A total of 19/30 (63%) patients and 33/60 (55%) joints had signs of TMJ involvement on MRI. This was associated with condylar deformity in 9/19 (47%) patients and 15/33 (45%) joints. Rheumatological, orthodontic and US examinations correctly diagnosed 11 (58%), 9 (47%) and 6 (33%) patients, respectively, with active TMJ arthritis, but misdiagnosed 8 (42%), 10 (53%) and 12 (67%) patients, respectively, as having no signs of inflammation. The best predictor for active arthritis on MRI was a reduced maximum mouth opening.

Conclusion. None of the methods tested was able to reliably predict the presence or absence of MRI-proven inflammation in the TMJ in our cohort of JIA patients. US was the least useful of all methods tested to exclude active TMJ arthritis.

Methods. Data from 10 108 RA patients enrolled in the Consortium of Rheumatology Researchers of North America registry were examined, including 649 patients initiating DMARD therapy. CDAI cut-off points for disease activity levels and responses were derived using receiver operating characteristic curves with the DAS28 and EULAR response criteria as gold standards. The -statistics were applied to assess agreement between CDAI-derived and EULAR-defined responses, as well as ACR20 and ACR50 with mACR20- and mACR50-defined responses, respectively.

Results. For the components of the EULAR response, the derived CDAI cut-off points for DAS28 levels of 3.2 and 5.1 were 7.6 and 19.6, respectively. The derived CDAI cut-off points were 4.3 and 10.0 for DAS28 changes of 0.6 and 1.2, respectively. There were moderate to substantial agreements between CDAI-derived and EULAR responses ( = 0.57–0.71). Agreement of ACR20 and ACR50 with mACR20 and mACR50 responses, respectively, was excellent ( = 0.88–0.95).

Conclusions. Agreement between composite measures of response without acute-phase reactants and standard measures ranged from moderate to excellent. The mACR20 and mACR50 criteria as well as CDAI-derived response criteria, can serve as composite measures of response in clinical practice and research settings without access to acute-phase reactants.

Methods. This was a prospective multi-centre longitudinal study of SLE patients. At every assessment, data were collected on disease activity (BILAG-2004 index) and treatment. Analyses were performed using overall BILAG-2004 index score (as determined by the highest score achieved by any of the individual systems) and all the systems scores. Sensitivity to change was assessed by determining the relationship between change in disease activity and change in therapy between two consecutive visits. Statistical analyses were performed using multinomial logistic regression.

Results. There were 1761 assessments from 347 SLE patients that contributed 1414 observations for analysis. An increase in therapy between visits occurred in 22.7% observations, while 37.3% had a decrease in therapy and in 40.0% therapy was unchanged. Increase in overall BILAG-2004 index score was associated with increase in therapy and inversely associated with decrease in therapy. Decrease in overall BILAG-2004 index score was associated with decrease in therapy and was inversely associated with increase in therapy. Changes in overall BILAG-2004 index score were differentially related to change in therapy, with greater change in score having greater predictive power. Increase in the scores of most systems was independently associated with an increase in treatment and there was no significant association between decreases in the score of any system with an increase in therapy.

Conclusions. The BILAG-2004 index is sensitive to change and is suitable for use in longitudinal studies of SLE.

Methods. This study included 127 patients with SSc as well as patients with SLE (n = 33), DM/PM (n = 21), RA (n = 13) and APS (n = 12), and 20 healthy subjects. Red blood cell velocity was evaluated using frame-to-frame determination of the position of capillary plasma gaps.

Results. The mean red blood cell velocity was significantly decreased in patients with SSc compared to healthy controls (63.0% reduction) and patients with other conditions. Mean blood velocity was similar between patients with dcSSc and lcSSc. Importantly, even SSc patients with normal or non-specific nail-fold video capillaroscopic (NVC) patterns or a scleroderma early NVC pattern exhibited a significantly lower red blood cell velocity compared to healthy controls (51.7 and 61.4% reduction, respectively) or patients with other conditions, despite normal or mild capillary changes. Patients with the scleroderma active and late NVC pattern showed a more decreased blood velocity (65.5 and 66.2% reduction, respectively). This reduced blood velocity was significantly associated with NVC findings, including capillary ramification and capillary loss. Although remarkably reduced velocity was observed in SSc patients with intractable digital ulcers (72.1% reduction), it was significantly improved by lipo-prostaglandin E₁ (lipo-PGE₁) infusion.

Conclusion. Our results suggest that reduced blood velocity is a hallmark of SSc. Furthermore, measurement of red blood cell velocity may be useful in evaluating therapeutic effects on microcirculation.