Immunopathology of IgA pemphigus

Abstract

Cases with vesiculo-pustular skin lesions showing anti-keratinocyte cell surface autoantibodies of exclusively IgA class have been identified.1–19 Although these cases were reported under a number of different names, the term “IgA pemphigus” is now used most commonly. In 1982, Wallach et al. first described a case demonstrating IgA deposition diffusely in the upper part of the epidermis.6 This staining pattern of IgA deposition, however, was quite different from the cell surface staining pattern seen in other cases of IgA pemphigus. Therefore, the antigen molecule for this particular case should be different from other cases, and, therefore, I do not include this type of IgA pemphigus in the present review. So far, more than 60 cases of IgA pemphigus have been reported.5 These previous reports indicate that, as classic pemphigus is subdivided into two types, IgA pemphigus can also be divided into two major subtypes, subcorneal pustular dermatosis (SPD) type7–9 and intraepidermal neutrophilic IgA dermatosis (IEN) type.10–16 It is now well known that IgG anti-keratinocyte cell surface autoantibodies in classic pemphigus or paraneoplastic pemphigus (PNP) react with the structural components of desmosomes.20–30 Therefore, autoantigens for IgA antibodies in IgA pemphigus are also considered to relate to desmosomes. Desmosomal cadherins are of two types, desmoglein (Dsg) and desmocollin (Dsc), both of which occur as three isoforms, Dsg1, 2 and 3, and Dsc1, 2 and 3.21 Classic pemphigus is divided into pemphigus foliaceus (PF) and pemphigus vulgaris (PV), IgG antibodies of which have been revealed to react with Dsg1 and Dsg3.22–30 A novel enzyme-liked immunosorbent assay (ELISA) using recombinant proteins of Dsg1 and Dsg3 produced by baculovirus expression system has been shown to be a highly sensitive and specific assay to detect autoantibodies in the sera of PF and PV.31–33 In our previous review for IgA pemphigus, history, terminology, and clinico-pathologic features of IgA pemphigus are discussed in detail.3 Therefore, in this review, I focus on the recent advances in the studies of immunopathology in IgA pemphigus, particularly on the identification of its target antigens.