Subclass Characteristics of IgG Autoantibodies in Bullous Pemphigoid and Pemphigus

Abstract

Immunoglobulin (Ig) G subclasses in anti-basement membrane zone (BMZ) autoantibodies found in the sera of bullous pemphigoid (BP) and in anti-intercellular substance (ICS) autoantibodies of pemphigus were investigated using immunofluorescent (IF) staining. In BP, IgG4, IgG1, and IgG2 were detected in 13, 5 and 6 of 15 patients, respectively; IgG3 was not detected. In pemphigus, IgG4 was detected in all of 10 patients, IgG1 in 7, IgG2 in one, and IgG3 in one patient, respectively. In both BP and pemphigus, the most prominent subclass in intensity of IF staining was IgG4. Although one BP and one PV patient had only IgG4 autoantibodies, C3 deposition was detected. The quantification of IgG subclasses in the sera of the patients was performed by enzyme-linked immunosorbent assays (ELISA). Serum levels of IgG4 in both BP and pemphigus were elevated approximately 3-fold over those in normal controls; those of whole IgG and IgG1-3 were not significantly elevated. Using direct IF staining, the deposition of C3 at the BMZ and at the ICS was demonstrated in 9 of 10 BP and in 3 of 8 pemphigus patients, respectively. The prominent IgG subclasses of anti-BMZ and anti-ICS antibody were IgG4, a noncomplement-fixing antibody, suggesting that the deposition of C3 in the lesional skin occurred via the alternative pathway, or that small amounts of IgG1-3 subclass autoantibodies activated the classical pathway.

Increased Immunoglobulin (Ig) G4–Positive Plasma Cell Density and IgG4/IgG Ratio Are Not Specific for IgG4-Related Disease in the Skin

“…IgG4/IgG ratios are greater than 0.40. response, 22,23 is implicated in the development of pemphigus. [24][25][26] Although the pathogenesis of IgG4-RD is not entirely understood, contributing factors include genetic predisposition, bacterial infection with molecular mimicry, and Th2-related autoimmunity. 22 In IgG4-RD, elevated IgG4 may function in tissue destruction or, more likely, may arise in response to an undefined inflammatory trigger.…”

Immunoglobin G4‐hepatopathy

“…Comparing cases of pemphigus vulgaris, IgG4-type autoantibodies react to the cell adhesion molecule desmoglein-3. 21 In some ethnic groups, pemphigus vulgaris is associated with HLA-DRB1*0402, and HLA-DRB1*0402 molecules may form a complex with peptides produced by the processing of desmoglein-3. Such peptides stimulate specific T cells, which secrete cytokines and promote the production of desmoglein-3-specific IgG4-type antibodies, resulting in the formation of skin lesions.…”

IgG4‐related systemic disease and lymphoplasmacytic aortitis

“…IgG4 is the least abundant of all serum IgG isotypes, comprising only ϳ6% of the total IgG in healthy individuals (37). Serum IgG4 levels have been reported to be elevated in conditions that bear little obvious resemblance to autoimmune pancreatitis and related disorders, such as human filariasis, pemphigus vulgaris, and pemphigus foliaceus (38)(39)(40). IgG4 is effectively a monovalent antibody, which generally binds antigens poorly and does not fix complement (37).…”