DIFFERENCES IN THE ANTIBASEMENT MEMBRANE ZONE ANTIBODIES IN OCULAR AND PSEUDO-OCULAR CICATRICIAL PEMPHIGOID

Purpose. Ocular cicatricial pemphigoid (OCP) is a chronic autoimmune c icatrizing disease which affects the conjunctiva and other squamous ep ithelium, resulting in a scarring process. A similar process, limited only to the conjunctiva, observed in some patients using eye drops for the treatment of glaucoma, is called pseudo-ocular cicatricial pemphi goid (P-OCP). Immunofluorescence studies demonstrate deposition of imm unoglobulins and complement components in the basement membrane zone ( BMZ) of the conjunctiva and an anti-basement membrane zone antibody in the serum of patients. A striking association between OCP and MHC cla ss II gene DQB10301 has been observed. The purpose of this study was to determine some of the differences in the binding of OCP and P-OCP s era to different lysate in an immunoblot assay, in an attempt to parti ally characterize the OCP and P-OCP antigens. Furthermore, we wanted t o determine if the MHC class II gene association of P-OCP is similar t o that of OCP. Methods. We studied sera from 11 patients with active o cular cicatricial pemphigoid and seven patients with pseudo-ocular cic atricial pemphigoid and controls. Indirect immunofluorescence (IIF) st udies were done using monkey esophagus and salt split normal human ski n as substrate. A sensitive immunoblot assay (IBA) was developed using normal human epidermis, dermis and conjunctiva as substrate. Typing f or MHC class II genes was performed on eight pseudo-ocular cicatricial pemphigoid patients by dot-blot analysis and compared to 38 matched c ontrols. Results. Weak staining of the basement membrane zone was obse rved in nine of ten ocular cicatricial pemphigoid sera and five of sev en pseudo-ocular cicatricial pemphigoid sera in the IIF assay using mo nkey esophagus. Using salt split human skin as substrate, ten of eleve n ocular cicatricial pemphigoid sera demonstrated low titer weak bindi ng to the epidermal side of the split. No consistent pattern of staini ng was seen with pseudo-ocular cicatricial pemphigoid sera. Ten of the 11 ocular cicatricial pemphigoid sera demonstrated binding to 230, 20 5, 160 and 85 kDa proteins in the IBA using normal human epidermis and conjunctiva lysates. When the lysates were first reacted with BP sera and then immunoblotted with ocular cicatricial pemphigoid sera, the 2 30, 160, and 86 kDa bands disappeared, and only the 205 kDa band persi sted. The sera of five of seven pseudo-ocular cicatricial pemphigoid p atients bound to 290, 230, 205, 180, 97, and 85 kDa proteins in the ep idermis and conjunctiva. However, the 230, 205, 180, and 85 kDa protei ns are depleted when the lysates are first reacted with BP and ocular cicatricial pemphigoid sera. In the dermal lysate, the pseudo-ocular c icatricial pemphigoid sera recognize 400, 290, 150 and 45 kDa proteins . None of these are absorbed by BP, ocular cicatricial pemphigoid or p emphigus vulgaris or epidermolysis bullosa acquisita sera. The 290 kDa proteins identified in the dermis and epidermis are distinct from eac h other. No binding was seen with control sera with the 3 lysates. Sta tistically, dot-blot analysis did not demonstrate a significant increa se in the frequency of the MHC DQB10301 gene. Conclusions. Patients w ith ocular cicatricial pemphigoid and pseudo-ocular cicatricial pemphi goid produce several autoantibodies. However, there are similarities a nd differences between them. The MHC class II genes associated with ps eudo-ocular cicatricial pemphigoid are different from those with ocula r cicatricial pemphigoid. This provides a new model system to study th e immune abnormalities in idiopathic and drug-related organ specific a utoimmunity.