Juvenile chronic arthritis, chronic iridocyclitis, and reactivity to histones.

Autoimmune rheumatic diseases in childhood present major differences in both clinical and laboratory features compared with adult onset disease.' Although polyarthritis occurs in both adults and children, the specific features of seropositive erosive rheumatoid arthritis are only seen in about 100/o of patients with juvenile chronic arthritis beginning under the age of 16 years.' 2 Most have seronegative disease-that is, without IgM rheumatoid factor, and serologically the more common finding is of antinuclear antibodies. These antibodies are detected in 30-400/o of all children with juvenile chronic arthritis, but are most common in late onset seropositive polyarthritis and in early onset pauciarticular disease. 5 These latter children with four or fewer joints affected in the first three months commonly have a limited arthritis, and with appropriate management usually have little long term disability. In antinuclear antibody positive pauciarticular arthritis beginning under the age of 5 years, however, 60-70% of children develop chronic iridocyclitis, which may cause blindness,6 and around 8O0/o of those affected are girls.7 It is not clear whether chronic anterior uveitis is an autoimmune disorder or an immune complex vasculitis.8 The initial cause of tissue damage may be physical trauma, infection, chemical, or immunological injury. Uveal damage caused by viruses or other microbial organisms may expose antigens, normally contained within cells, for subsequent autoimmune sensitisation. After an initial attack of uveitis it has been postulated that the endothelial lining of the uveal blood vessels may become permanently damaged, thereby reducing the effectiveness, of the blood/aqueous barrier.9 This would allow deposition of specific antinuclear antibody/ antigen complexes or the later deposition of unrelated immune complexes, which would then cause a recrudescence and perpetuation of inflammation.9-l" The rich blood supply of the uvea may trap immune complexes, and in nongranulomatous uveitis these are thought to be only moderate in size. Evidence for immune complex formation in pauciarticular juvenile chronic arthritis is limited, however. 12-15 Lack of lymphatic drainage to the eye reduces sequestration and processing of antigen by lymphoid tissue in peripheral nodes.'6 Primed lymphocytes return to the uvea and production of antibody occurs locally.9 The antigenic stimulus to antinuclear antibody formation in both adult rheumatoid arthritis and in juvenile chronic arthritis is unknown. Antinuclear antibodies are detectable on both HEp-2 cells and on rodent tissue substrate. The pattern of immunofluorescence may be speckled,'7 but is usually homogeneous,4 18 19 and suggests binding to the nucleosome, in which histones and DNA exist in a highly organised structure.20 Many authors have reported the uncommon existence of antibodies to double stranded DNA.2-26 Antibodies to single stranded DNA, though detectable in active juvenile chronic arthritis,'9 27 are also found in many other disorders and their pathogenic significance is uncertain.24 Also, none of the well characterised autoantibodies found in connective tissue diseases (including antibodies to Ro, La, RNP, Sm, PM-1, Scl-70) is present with any regularity. 17 21 25 2830 Attention recently has shifted towards further evaluation of antibodies to histones, and several authors have reported the presence of these antibodies in juvenile chronic arthritis.3138