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Originally published In Press as doi:10.1167/iovs.08-1971 on June 6, 2008
 (Investigative Ophthalmology and Visual Science. 2008;49:4476-4481.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.08-1971
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Associations of Seroreactivity against Crystallin Proteins with Disease Activity and Cataract in Patients with Uveitis

Ling Chen,1,2,3 Gary N. Holland,1,2,4 Fei Yu,1,2 Ralph D. Levinson,1,2 Kirsten J. Lampi,5 Joseph Horwitz,1,2 and Lynn K. Gordon1,2,4

1From the Ocular Inflammatory Disease Center, Jules Stein Eye Institute and the 2Departments of Ophthalmology and 3Pharmacology, David Geffen School of Medicine at the University of California, Los Angeles, California; the 4Ophthalmology Section, Greater Los Angeles VA Healthcare System, Los Angeles, California; and the 5Department of Oral Molecular Biology, Oregon Health and Science University, Portland, Oregon.

PURPOSE. βB1-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 βB1 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 {alpha}A-, {alpha}B-, βB1-, or βB2-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 {alpha}A-, {alpha}B-, or βB1-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 ≤ 0.01). Seroreactivity against {alpha}A-, {alpha}B-, or βB1-, but not βB2-crystallin was related to active anterior segment inflammation. Seroreactivity against {alpha}B and βB1 was significantly related to cortical cataract (P ≤ 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.






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