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(Investigative Ophthalmology and Visual Science. 1999;40:2283-2290.)
© 1999 by The Association for Research in Vision and Ophthalmology, Inc.

The Role of Antibody to Human ß4 Integrin in Conjunctival Basement Membrane Separation: Possible In Vitro Model for Ocular Cicatricial Pemphigoid

Roxanne Y. Chan1, Kailash Bhol2, Nattaporn Tesavibul1, Erik Letko1, Raymond K. Simmons2, C. Stephen Foster1 and A. Razzaque Ahmed2

1 From the The Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School; and the 2 Department of Oral Medicine and Diagnostic Sciences, Harvard School of Dental Medicine, Boston.

Abstract

PURPOSE. To demonstrate the specific binding of autoantibodies present in the sera of patients with ocular cicatricial pemphigoid (OCP) to human ß4 integrin present in the normal human conjunctiva (NHC) and to study the role of OCP autoantibodies and antibody to human ß4 integrin in the pathogenesis of subepithelial lesion formation in OCP.

METHODS. Indirect immunofluorescence assay and in vitro organ culture method using NHC were used. Sera and IgG fractions from 10 patients with OCP; immunoaffinity-purified OCP autoantibody; antibodies to human ß4, ß1, {alpha}6, and {alpha}5 integrins; and sera from patients with pemphigus vulgaris, bullous pemphigoid (BP), and chronic atopic and chronic ocular rosacea cicatrizing conjunctivitis; and normal human serum (NHS) were used.

RESULTS. Nine of 10 OCP sera or IgG fractions, immunoaffinity-purified OCP autoantibody, antibodies to human ß4 and {alpha}6 integrins, and sera from patients with BP showed homogenous, smooth linear binding along the basement membrane zone (BMZ) of the NHC. NHS, antibodies to other integrins, and sera from patients with chronic cicatrizing conjunctivitis from other causes showed no such binding. When NHC was first absorbed with OCP sera and then reacted with anti-ß4 antibodies or vice versa, the intensity of the BMZ binding was dramatically reduced or completely eliminated, indicating that there were autoantibodies in OCP sera specific for the ß4 integrin. BMZ separation developed 48 to 72 hours after addition of total OCP sera, IgG fractions from OCP sera, immunoaffinity-purified autoantibodies from sera of patients with OCP, or anti-ß4 antibodies to the NHC cultures, but not after addition of normal control sera, sera from patients with chronic cicatrizing conjunctivitis from causes other than OCP, or sera from patients with OCP in clinical remission.

CONCLUSION. Circulating anti-ß4 integrin antibody may have an important role in the pathogenesis of OCP.




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