Abstract
Purpose: :
Posterior uveitis encompasses a heterogeneous group of intraocular inflammatory conditions. While the cause of most posterior uveitides remains unknown, it is possible that humoral mechanisms play a pathogenetic role. In this study, we profiled the anti-retinal antibody activities of patients with posterior uveitis and compared them to those of normal controls and patients with retinal disease of non-inflammatory origin.
Methods: :
Patients with posterior uveitis (n=47), molecularly confirmed photoreceptor degenerations (n=11), and normal 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.
Results: :
Bands on Western blot representing retinal proteins bound by autoantibodies were found in normal controls, patients with posterior uveitis, and molecularly confirmed heritable retinal degenerations. In normal controls, 64% (95% CI: 45% - 80%) had circulating autoantibodies that recognized retinal proteins. Comparison of the ratio of soluble to insoluble bands on Western blot using Fisher’s exact test showed that the normal control group had a ratio favoring insoluble bands whereas patients with posterior uveitis (p<0.0001) and molecularly confirmed retinal degenerations (p=0.018) had ratios favoring soluble bands. A trend of increasing soluble bands was seen with increasing age in normal controls.
Conclusions: :
No statistical significance was found for the prevalence of bands between disease cohorts and normal controls. In addition, no consistent profile of autoantibody activity against specific retinal proteins was identified within disease groups. The non-infectious uveitides, consequently, do not appear amenable to characterization by autoantibody profiling. There was a higher prevalence of serum reactivity to the aqueous-soluble fraction (non-membrane-bound protein) of retinal proteins in patients with eye pathology and to the aqueous-insoluble fraction (membrane-bound protein) of retinal proteins in normal controls. The finding of increased reactivity to non-membrane-bound retinal proteins in patients with ocular pathology suggests that patients may develop anti-retinal antibodies to intracellular proteins as a result of damage to ocular tissues.
Keywords: uveitis-clinical/animal model • immune tolerance/privilege