Pemphigus vulgaris (PV) is a rare, potentially fatal, autoimmune disease that affects the skin and mucous membranes. The PV antigen (PVA) has been characterized as desmoglein 3. PV patients carry HLA-DR4-or HLA-DR6-bearing extended haplotypes. We recently demonstrated that patients with active disease have high titers of PV autoantibodies of the IgGl and IgG4 subclasses. Patients in remission, healthy unaffected relatives, and some MHCmatched normal individuals have low levels of PV autoanti-

Pemphigus vulgaris is an autoimmune blistering disease that is characterized by the presence of an antibody against an epidermal cell protein. In our previous studies, we have demonstrated that the presence of the antibody in the patients and in the healthy relatives of the patients strongly correlates with MHC haplotypes. The purpose of this study was to determine the subclasses of IgG present in the sera of patients with active disease, those in remission, healthy and unaffected relatives and normal controls. The presence of the autoantibody to the pemphigus antigen was assayed by a modified, sensitive immunoblot technique. The assay was considered positive if a 130-kD band was seen when normal human epidermis was used as a substrate. In patients with active disease, the sera contained antibodies of the IgG1 and IgG4 subclasses. The sera of patients in remission, those of healthy unaffected relatives and normal controls contained only the IgG1 subclass. The normal controls consist of MHC-matched and non-matched individuals. This study indicates that patients with disease activity have an antibody which is of the IgG1 and IgG4 subclasses, which we consider to be a pathogenic antibody. The sera of healthy relatives and normal controls that contain an antibody which binds to the pemphigus antigen is of the IgG1 subclass only and is considered to be a nonpathogenic or natural autoantibody. These observations provide the basis to study the immunoregulatory mechanisms and the production of normal and pathogenic antibodies.

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.

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