Rheumatology 2001; 40: 227-228
© 2001 British Society for Rheumatology
Letters to the Editor |
Familial erosive arthritis associated with seroreactivity to human intracisternal retroviral particle type I (HIAP-I)
Tulane University Medical and LSU Health Sciences Center, New Orleans, LA 70112-2822, USA
SIR, The potential role of retroviruses in the aetiopathogenesis of chronic inflammatory and/or autoimmune disorders has received a great deal of attention over the past few years [1]. Animal retroviruses induce many types of immune dysfunction, including immune deficiencies and autoimmune diseases. For example, caprine arthritis encephalitis virus, a replication-competent lentivirus distantly related to HIV, is the causative agent of chronic arthritis in goats [2]. In addition, defective endogenous retroviruses that are not lentiviruses may also play a role in a mouse model of systemic lupus erythematosus [3] and in the induction of an autoimmune–thyroid disease resembling Graves disease [4]. Of the known human retroviruses, only HIV-1, HIV-2 and HTLV-1 have been shown conclusively to cause disease. Recent studies have linked other human retroviruses, some newly discovered, such as human retroviruses-5 (HRV-5), to serious immune dysfunctions, including systemic or organ-specific autoimmune diseases and non-HIV immune deficiencies [1, 5]. Another recently identified human retrovirus is intracisternal A-type particle I (HIAP-1), found in the salivary glands of patients with Sjögren's syndrome [6]. Serum antibodies against HIAP-1 have been detected in patients with Sjögren's syndrome [7], Graves disease [8], idiopathic CD4 lymphocytopenia [9] and chronic biliary cirrhosis [1], raising the possibility of a similar causative agent in these various autoimmune conditions.
Here we report clinical and laboratory findings in a family arthritis cluster exhibiting serum antibody reactivity against proteins of the human intracisternal retroviral particle type I (HIAP-I).
Case 1 was a 38-yr-old man referred for evaluation of a 2-yr history of migratory arthritis of both hands associated with several hours of morning stiffness and fatigue. Physical examination revealed bilateral carpal, metacarpal and proximal interphalangeal synovitis with limitation in the range of motion. Laboratory findings were significant for an elevated rheumatoid factor, and normal complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein and negative antinuclear antibodies (ANA). HLA-B27 and HLA-DR4 antigens were negative. X-ray findings of the hands showed early erosive changes.
Case 2 was a 35-yr-old woman, the wife of case 1, who presented to our clinic with a 6-yr history of symmetrical arthritis over her feet and hands consistent with rheumatoid arthritis (RA). Physical examination revealed significant synovial hypertrophy of the wrists and the metacarpophalangeal and metatarsophalangeal joints. Laboratory findings were significant for positive ANA (1:160) speckled pattern and low positive rheumatoid factor, with normal CBC, ESR and C-reactive protein. HLA-B27 and HLA-DR4 were absent. X-ray findings of the right hand demonstrated periarticular demineralization and erosions of the first and second metacarpal heads. X-ray of the right foot showed pencilling of the head of the fifth metatarsal and calcification of the soft tissue of the plantar area with calcaneal entesopathic changes. Erosive changes were also present at the base of the articulating proximal phalanx of the fifth toe. In the left foot, erosive changes were seen around the head of the third metatarsal. Erosive changes, simulating pencilling, were also present at the head of the fifth metatarsal.
Case 3, a 16-yr-old woman, was the daughter of patients 1 and 2. She was evaluated for a 1-yr history of migratory arthritis, morning stiffness lasting several hours, and fatigue. Physical examination and laboratory findings were unremarkable. X-ray of the hands and feet did not show evidence of erosive disease and/or demineralization.
In all of the patients, there was no clinical evidence or family history of psoriasis and/or psoriatic arthritis, or other arthritides.
All patients and an asymptomatic 17-yr-old sibling were tested by immunoblotting for serum antibodies against HIV-1, HTLV-1 and HIAP. For the most part, none of the family members had a positive test against HIV-1 or HTLV-1. The exception was case 2, whose serum did have antibodies reactive to p24, the major gag protein of HIV-1. In contrast, however, each of the individuals from this family that exhibited arthritis demonstrated seroreactivity to HIAP-I proteins. The asymptomatic sibling, a male aged 17 yr, was seronegative for HIAP-I proteins.
Clinical, genetic and epidemiological lines of evidence suggest that autoimmune disease in man is consistent with an interaction between genetic susceptibility and external triggering factors such as microbial agents. At present, viruses are the leading candidates, particularly retroviruses.
Detection of serum antibodies against HIAP-I proteins in symptomatic individuals belonging to the same family is of great interest primarily because prior studies have indicated that fewer than 3% of adult RA patients have serum antibodies to HIAP-I. These results highlight the unusual nature of this familial cluster of arthritis patients. Although A-type retroviruses of rodents, and presumably also humans, are defective, they can be passed vertically (in the germ line). There is also the possibility that these agents could become infectious by phenotypic mixing with other human endogenous retroviruses, such as HERV-KIO, that encode functional envelope genes. Horizontal transmission of phenotypically mixed HIAP could explain the presence of a serological response to this agent in both the husband and the wife (and perhaps their daughter). Prior studies have suggested that A-type viruses might be inherited and have limited infectivity. It is also possible that other environmental or hereditary factors could have contributed to the development of rheumatic disease in this family.
The clinical and radiological findings were somewhat atypical for RA. Of interest, the presence of entesopathic and destructive changes (erosions) have been described in HIV-associated reactive arthritis [10]. In summary, serum reactivity against HIAP-I proteins was associated with erosive arthritis in a family cluster, suggesting a possible causative role for this retroviral agent.
Notes
Correspondence to: L. R. Espinoza. 
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