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Roxanne Y. Chan, Kailash Bhol, Nattaporn Tesavibul, Erik Letko, Raymond K. Simmons, C. Stephen Foster, A. Razzaque Ahmed; The Role of Antibody to Human β4 Integrin in Conjunctival Basement Membrane Separation: Possible In Vitro Model for Ocular Cicatricial Pemphigoid. Invest. Ophthalmol. Vis. Sci. 1999;40(10):2283-2290.
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© ARVO (1962-2015); The Authors (2016-present)
purpose. To demonstrate the specific binding of autoantibodies present in the
sera of patients with ocular cicatricial pemphigoid (OCP) to human β4
integrin present in the normal human conjunctiva (NHC) and to study the
role of OCP autoantibodies and antibody to human β4 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 β4,β
1, α6, and α5 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)
results. Nine of 10 OCP sera or IgG fractions, immunoaffinity-purified OCP
autoantibody, antibodies to human β4 and α6 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-β4 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 β4 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-β4 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-β4 integrin antibody may have an important role in
the pathogenesis of OCP.
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