SummaryPemphigus vulgaris (PV) is an autoimmune disease caused by high concentrations of antibody to an epidermal cadherin. The disease is associated with two kinds of HLA-DR4, DQ8 haplotypes dominantly distributed among Jewish patients, and these plus DR6, DQ5 haplotypes in nonJewish patients. Low levels of the PV antibody were found in 48% of a total of 120 asymptomatic parents, children, and siblings of 31 patients, thus exhibiting dominant inheritance. The inheritance of these low levels of antibody in asymptomatic relatives was linked to the major histocompatibihty complex with a highly significant logarithm of the odds score of 9.07, almost always to a DR4 or DR6 haplotype of the patient. Disease appears to occur in susceptible individuals with low levels of antibody when a second factor, either environmental or genetic, induces high levels, sufficient to produce blisters.

Ocular cicatricial pemphigoid (OCP) is an autoimmune blistering disease that affects the conjunctiva and multiple mucous membranes. Class I and H and complement genetic markers of the major histocompatibility complex were studied in 20 Caucasian OCP patients and members of their families. Frequencies of individual alleles and common fixed or extended haplotypes in the patients were compared with those in normal family control haplotypes and with overall normal Caucasian haplotypes. The most striking increase compared with overall controls was noted in HLA-DQw3 (P = 0.006), unassociated with any extended haplotype. All but 1 of the 20 patients carried DQw3 in linkage with HLA-DR4 (increased significantly with P = 0.042 compared with overall normal genotype controls) or DR5. The DQw3, on analysis by restriction fragment length polymorphism in genomic DNA, was, in every instance, DQw7 (3.1, DQB1*0301). The frequency of DQB1*0301 in patient haplotypes compared with overall normal DR4 and DR5 DQw3-bearing haplotypes was statistically significantly increased (P < 0.003, relative risk = 9.6). The distribution of homozygotes and heterozygotes for DQB1*0301 among the patients was consistent with dominant but not recessive inheritance of DQB1*0301 or a gene, probably a class H allele, in linkage disequilibrium with it as the major histocompatibility complex susceptibility gene for OCP.Ocular cicatricial pemphigoid (OCP) is an autoimmune blistering disease that affects multiple mucous membranes (1-3). If not treated or treated inappropriately when it affects the eyes, it can cause blindness. The pathologic processes of chronic cicatrizing conjunctivitis and progressive conjunctival subepithelial fibrosis that characterize this disease result in severe xerosis of the eye and ocular keratinization.The deposition of immunoglobulins and complement components at the basement membrane zone (BMZ) (4-6) of the involved mucosa appears to be pathogenetic. Inflammatory mediators in the preocular tear film contribute to the final pathologic changes (3). Circulating antibodies to BMZ have been demonstrated in the serum of OCP patients, using skin and buccal mucosa as substrate (7,8).There have only been a few studies of HLA antigen frequencies in patients with OCP. The initial reports (6, 9) of an increased frequency of HLA-B12 (HLA-B44 or B45) were not confirmed in later studies (3, 10). Recently (11), we reported an increase in the frequency of the HLA-DR4 allele in OCP patients. In patients with pemphigus vulgaris, the increased frequency of DR4 is ascribable to the increased frequency oftwo haplotypes, SC21, DR4, DQw8] and SC31, DR4, DQw8], particularly in Ashkenazi Jewish patients (12). The first of these is a known extended haplotype (13) (a haplotype with fixed DNA over at least the HLA-B/DR interval) in this ethnic group. In a number of major histocompatibility complex (MHC) alleleassociated diseases, the increase in specific alleles is secondary to the increase in one or more extended haplotypes that carry suscepti...

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Evidence is presented that cobra venom factor, the anticomplementary protein in Naja naja venom, is modified cobra C3 (the third component of complement). Antiserum to the cobra venom factor cross reacts with human C3. A protein in cobra serum reacts strongly with antiserum to the venom factor and the former protein, like human C3, is converted by incubation of cobra serum with endotoxin, hydrazine, or simple storage at 37 degrees C. Incubation of cobra venom factor with cobra serum destroys the C3 cleaving activity of the venom factor in human serum, whereas human C3b inactivator is ineffective. Thus, the cobra venom factor appears to be a form of C3 (perhaps C3b); its potent action in human serum probably derives from its lack of sensitivity to human C3b inactivator.