Pemphigus vulgaris is an autoimmune blistering disease that is charact
erized by the presence of an antibody against an epidermal cell protei
n. In our previous studies, we have demonstrated that the presence of
the antibody in the patients and in the healthy relatives of the patie
nts strongly correlates with MHC haplotypes. The purpose of this study
was to determine the subclasses of IgG present in the sera of patient
s with active disease, those in remission, healthy and unaffected rela
tives and normal controls. The presence of the autoantibody to the pem
phigus antigen was assayed by a modified, sensitive immunoblot techniq
ue. The assay was considered positive if a 130-kD band was seen when n
ormal human epidermis was used as a substrate. In patients with active
disease, the sera contained antibodies of the IgG1 and IgG4 subclasse
s. The sera of patients in remission, those of healthy unaffected rela
tives and normal controls contained only the IgG1 subclass. The normal
controls consist of MHC-matched and nonmatched individuals. This stud
y indicates that patients with disease activity have an antibody which
is of the IgG1 and IgG4 subclasses, which we consider to be a pathoge
nic antibody. The sera of healthy relatives and normal controls that c
ontain an antibody which binds to the pemphigus antigen is of the IgG1
subclass only and is considered to be a nonpathogenic or natural auto
antibody. These observations provide the basis to study the immunoregu
latory mechanisms and the production of normal and pathogenic antibodi
es.