Rheumatology Advance Access originally published online on March 23, 2007
Rheumatology 2007 46(5):885-886; doi:10.1093/rheumatology/kem032
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LETTERS TO THE EDITOR |
Torquetenovirus in patients with arthritis
1Virology Section and Retrovirus Center, Department of Experimental Pathology, University of Pisa, Pisa, Italy and2Rheumatology Unit, University of Pisa, Pisa, Italy Present Address: S. Specter, Department of Molecular Medicine, University of South Florida, Tampa, FL, USA.
Correspondence to: Mauro Bendinelli. E-mail: bendinelli{at}biomed.unipi.it
SIR, Inflammatory joint diseases affect many individuals and can lead to severe disability. Factor(s) and mechanism(s) that lead to joint damage remain elusive. Studies indicate that genetic determinants and environmental factors are important, but that an outside agent possibly initiates pathology [1]. Viruses have been considered as possible aetiological links, but the results remain inconclusive [2].
Torquetenovirus (TTV), one of the three members of the freestanding Anellovirus genus of viruses, when discovered in 1997 was believed to be involved in liver disease. However, subsequent study revealed a high prevalence of the virus in healthy subjects [3, 4]. Indeed, TTV DNA is chronically present in the plasma (mean viral load: 4–5 log10 copies/ml), tissues and bodily fluids of >80% of healthy blood donors, making it difficult to demonstrate possible disease associations with reasonable certainty [5]. As a further compounding element, TTV shows considerable genetic diversity, being classified in over forty genotypes grouped into five genogroups (designated 1–5) that might possess different pathogenic potentials.
Recent reports have suggested that TTV might be associated with autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and others [6–8]. The present study included 136 patients with arthritis consecutively referred to the Rheumatology Unit, University of Pisa: according to established clinical criteria for each condition, 55 had psoriatic arthritis (PsA), 51 RA and 30 ankylosing spondilitis (AS). Of these, 51 were being treated with disease-modifying anti-rheumatic drugs and 29 also received steroids. Control groups included 74 healthy blood donors or laboratory personnel, 54 patients with SLE and 39 subjects with psoriasis but no joint involvement. Informed consent was obtained from all subjects enrolled in the study.
TTV infection was assessed by testing plasma in triplicate with a real-time PCR assay on the untranslated region of the viral genome as described previously [9, 10]. The rate of TTV infection was 93% in healthy controls and was similar in all groups with the exception of RA patients who had a lower TTV prevalence, although it was still 80% (Table 1). The highest viral loads were seen in patients with PsA, and significantly higher viral loads vs healthy controls were seen in AS, PsA and SLE patients. It is interesting to note that the TTV loads of patients with PsA were also significantly higher than in those with psoriasis only (Table 1).
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Characterization using 5 separate genogroup-specific PCR assays [10] of the TTV present in 137 of the study patients showed that over half were infected with more than one genogroup (78/137). The arthritis group had a significantly greater proportion of subjects with
3 different TTV genogroups compared with healthy subjects (24/67 vs 4/29; P = 0.029). Genogroups 1 (82 people) and 3 (90 people) were most common and genogroup 2 (4 people) was least common. Because among this subgroup of subjects TTV genogroup 4 infections were statistically more common in arthritis patients as compared with healthy subjects (data not shown), we extended the genogroup 4-specific analysis to all the TTV positive individuals in the study, except 3 with SLE for whom we had no further plasma available. This resulted in a more frequent detection of genogroup 4 in arthritis patients (particularly those with PsA and RA) vs healthy subjects (Table 1). The current report systematically examined several rheumatic diseases and the relationship to TTV load and genogroups. Patients with AS, PsA and SLE had elevated plasma TTV loads when examined separately compared with healthy subjects, but RA patients did not. Further analysis detected genogroup 4 TTV in patients with arthritis more commonly as compared with healthy subjects, suggesting that this genogroup is most likely to have a significant role in the relationship between TTV and disease pathology. The latter finding is consistent with previous observations from this laboratory regarding genogroup 4 and disease [9].
Collectively, the present findings are compatible with a possible association between florid TTV replication and arthritis. While TTV, or a specific genogroup within it, might contribute to the triggering of autoimmunity in rheumatic disorders, one must consider the converse, that these disorders might trigger TTV replication. Furthermore, one can consider that some mutual stimulation of TTV replication and autoimmune reactivity may keep viral load and disease severity in a perpetual state of flux. Prospective, well-designed studies are necessary to determine which one, if any, of these possibilities holds true.
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Acknowledgement |
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This work was supported in part by grants Ministero dell’Istruzione, dell’Università e della Ricerca (Rome, Italy).
The authors have declared no conflicts of interest.
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TopAcknowledgementReferences |
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- Silman AJ and Pearson JE. (2002) Epidemiology and genetics of rheumatoid arthritis. Arthritis Res 4:S265–72.[CrossRef][Medline]
- Masuko-Hongo K, Kato T, Nishioka K. (2003) Virus-associated arthritis. Best Pract Res Clin Rheumatol 17:309–18.[CrossRef][Medline]
- Nishizawa T, Okamoto H, Konishi K, Yoshizawa H, Miyakawa Y, Mayumi M. (1997) A novel DNA virus (TTV) associated with elevated transaminase levels in posttransfusion hepatitis of unknown etiology. Biochem Biophys Res Commun 241:92–7.[CrossRef][Web of Science][Medline]
- Bendinelli M, Pistello M, Maggi F, Fornai C, Freer G, Vatteroni ML. (2001) Molecular properties, biology, and clinical implications of TT virus, a recently identified widespread infectious agent of humans. Clin Microbiol Rev 14:98–113.
[Abstract/Free Full Text] - Pollicino T, Raffa G, Squadrito G, et al. (2003) TT virus has a ubiquitous diffusion in human body tissues: analyses of paired serum and tissue samples. J Viral Hepat 10:95–102.[CrossRef][Web of Science][Medline]
- Gergely P Jr, Perl A, Poor G. (2006) Possible pathogenic nature of the recently discovered TT virus. Does it play a role in autoimmune rheumatic diseases? Autoimmunity Rev 6:5–9.[CrossRef]
- Gergely P Jr, Pullmann R, Stancato C, et al. (2005) Increased prevalence of transfusion-transmitted virus and cross-reactivity with immunodominant epitopes of the HRES-1/p28 endogenous retroviral autoantigen in patients with systemic lupus erythematosus. Clin Immunol 116:124–34.[CrossRef][Web of Science][Medline]
- Sospedra M, Zhao Y, zur Hausen H, et al. (2005) Recognition of conserved amino acid motifs of common viruses and its role in autoimmunity. PloS Pathogens 1:335–48.[Web of Science]
- Maggi F, Pifferi M, Fornai C, et al. (2003) TT virus in the nasal secretions of children with acute respiratory diseases: relationship to viremia and severity. J Virol 77:418–25.
- Maggi F, Andreoli E, Lanini L, et al. (2005) Relationships between total plasma load of torquetenovirus (TTV) and TTV genogroups carried. J Clin Microbiol 43:4807–10.
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