Seroreactivity Against Aqueous-Soluble and Detergent-Soluble Retinal Proteins in Posterior Uveitis

Abstract

To characterize the seroreactivity against retinal proteins in patients with posterior uveitis, retinal disease of noninflammatory origin, and healthy controls. Patients with posterior uveitis (n=47), molecularly confirmed photoreceptor degenerations (n=11), and healthy controls (n=33) received dilated fundus examinations at the University of Iowa. Aqueous-soluble and detergent-soluble fractions of human retina were separated by gel electrophoresis and transferred to polyvinylidene fluoride membranes. Membranes were probed with patient serum samples to detect IgG, IgA, and IgM human antibodies that react with retinal antigens. The number of bands detected by Western blot was counted, and their molecular weights were determined. Antibodies recognizing retinal proteins were found in healthy controls, in patients with posterior uveitis, and in patients with molecularly confirmed heritable retinal degenerations. In healthy controls, 42% of individuals had circulating autoantibodies that recognized retinal proteins. Healthy controls had a low odds ratio of serum reactivity to soluble antigens (0.7; 95% confidence interval [CI], 0.4-1.2). Patients with inflammatory retinal diseases and inherited retinal diseases had 4.89 (95% CI, 2.25-10.64; P<.001) and 2.71 (95% CI, 1.19-6.16; P=.02) times more activity against soluble retinal antigens compared with controls. Healthy control patients exhibited a significantly higher level of background autoantibody activity against retinal proteins than previously reported. Antibody activity in healthy controls was primarily directed against membrane-bound retinal proteins, whereas in patients with pathologic retinal conditions, antibodies targeting nonmembrane-bound retinal proteins predominate.