Associations of seroreactivity against crystallin proteins with disease activity and cataract in patients with uveitis

Abstract

Purpose: betaB1-crystallin is a putative target of an autoantibody observed in a subset of patients with uveitis. The purpose of this study was to determine whether seroreactivity against betaB1 or other specific purified crystallin proteins is observed in patients with uveitis and whether this reactivity is associated with either cataract or active intraocular inflammation.

Methods: Sera from patients with uveitis were tested for IgG antibodies with reactivity against alphaA-, alphaB-, betaB1-, or betaB2-crystallin proteins using a modified slot-blot protocol. Ophthalmic evaluations included analysis of the degree of intraocular inflammation and assessment of lens opacity by the Lens Opacities Classification System (LOCS) III. Positive anti-crystallin reactivity was defined as greater than the mean + 2 SD of the reactivity of a commercially available control serum panel. Statistical analysis was performed with the Fisher exact test, Kruskal-Wallis test, and Student's t-test.

Results: IgG antibodies against alphaA-, alphaB-, or betaB1-crystallin were identified in 70% of 39 subjects; in contrast, only 30% of the control sera exhibited reactivity against one or more of these crystallin proteins (P <or= 0.01). Seroreactivity against alphaA-, alphaB-, or betaB1-, but not betaB2-crystallin was related to active anterior segment inflammation. Seroreactivity against alphaB and betaB1 was significantly related to cortical cataract (P <or= 0.05).

Conclusions: Serum antibodies against specific crystallin proteins are present in most patients with uveitis. The relationship between the presence of specific anti-crystallin antibodies and active inflammation may indicate a role for these autoantibodies in uveitis pathogenesis.

Figure 1

Seroreactivity against crystallins in patients with uveitis and in normal control subjects. Horizontal dashed line: the mean + 2 SD of normal controls. Represented are seroreactivities against (A) αA-, (B) αB-, (C) βB1-, and (D) βB2-crystallins, respectively.