Iris Protein Antibodies in Serum of Patients with Juvenile Rheumatoid Arthritis and Uveitis

Abstract

Homogenates of bovine iris were fractionated by gel filtration chromatography, and the column-eluted proteins were probed with pooled sera obtained from patients with pauciarticular juvenile rheumatoid arthritis (JRA). The serum pool prepared from patients with pauciarticular JRA and a history of anterior uveitis, but not from those without the eye disease, contained IgG antibodies which bound a low molecular weight iris antigen (LMW-IA) as measured by a modified ELISA. LMW-IA was protease-sensitive and contained at least four proteins of approximate molecular weights of 16, 13, 9 and 6.5 kD with no uronic acid or carbohydrate. Analysis of individual patient sera for IgG anti-LMW-IA antibody demonstrated that 1/20 (5%) pediatric non-rheumatic disease controls (NRDC), 1/19 (5.3%) non-uveitic pauciarticular JRA patients and 6/21 (28.6%) uveitic pauciarticular JRA patients were positive by ELISA. Levels of anti-LMW-IA antibody did not correlate with serum IgG concentration, the presence of IgG antibody to soluble retinal S antigen (S antigen) or reactivity to the low molecular weight fraction of bovine choroid (LMW-C). Ten of 21 (47.6%) children with pauciarticular JRA and uveitis had serum antibody that reacted with LMW-IA and/or retinal S antigen as compared to 1/20 (5%) NRDC patients and 3/19 (15.8%) patients with pauciarticular JRA uncomplicated by uveitis. Analysis of patient immunoreactivity to proteins of the anterior uveal tract may provide a greater understanding of pathogenic features related to arthritis-associated eye disease.

Inflammatory Arthritic Process, Iridocyclitis and Immune Response to Articular and Ocular Antigens in Wistar Rats Injected with T. gondii Trophozoites

“…One of the most striking findings of our study is that 70% of the animals injected with T. gondii developed antibodies against retinal S antigen and iris antigens, but only 40% showed iridocyclitis. This finding was similar to that observed in patients with juvenile rheumatoid arthritis, who develop antibodies directed against epitopes in iris, retinal blood vessels, ciliary body, retinal S protein and collagen with and without uveitis [16,[33][34][35]. In this type of chronic inflammatory arthritis, chronic anterior uveitis appears as a serious complication in 20% of cases [36,37].…”

“…Soluble retinal S antigen was prepared from bovine retina by the method of Dorey et al [15]. Homogenate of bovine iris was prepared following the procedure described by Hunt et al [16]. Briefly, iris tissue was carefully removed and then dissociated in four parts (w/v): 0.01 M phosphate-buffered 0.14 M saline (PBS), pH 7.3 with 0.001 M EDTA, 0.0001 M and 0.04% N 3 Na.…”

Correlation Between Disease Severity and Presence of Ocular Autoantibodies in Juvenile Idiopathic Arthritis-Associated Uveitis

“…8,10,[17][18][19][20] The presence of specific antiocular serum antibodies has been investigated in patients with JIAU. Herein, serum antibodies directed against a low molecular weight antigen extracted from bovine iris or against lens crystallins, and against retinal S-antigen have been described 9,21,22 ; the latter is being used for induction of uveitis in several animal models.…”

“…5,6 There is profound evidence that the presence of serum antinuclear antibodies (ANA) is a risk factor for the development of uveitis. 2,3 Some studies have shown that autoantibodies directed against nuclear histone and nonhistone proteins, or against a low-molecular bovine iris antigen or soluble retinal antigen (S-Ag) [7][8][9][10] correlated with uveitis occurrence. However, their pathogenetic role is unclear.…”

Autoantibodies specificity in acute anterior uveitis according to the presence of the HLA-B27 allele

“…[27][28][29][30] Antibodies directed at antigens unique to the iris have also been demonstrated, principally in uveitis associated with juvenile rheumatoid arthritis. [36][37][38] The present study was undertaken to evaluate HLA-B27-positive (HLA-B27ᮍ) and HLA-B27-negative (HLA-B27Ø) patients with AAU in relation to the frequency and specificity of autoantibodies against antigens of the anterior uveal tract and non-ocular tissues.…”