Can immunohistochemistry replace immunofluorescence in diagnosis of skin bullous diseases?

Abstract

Autoimmune bullous diseases are distressing and sometimes risky bullous dermatoses characterized by the presence of antibodies focused against disease-specific target antigens. Recognition of these antibodies using immunofluorescence is used to be the only sure diagnostic method after reviewing the routine histopathological section. Because of many causes that make the using of immunofluorescence difficult, we tried to evaluate the role of immunohistochemistry in diagnosis of these bullous skin diseases; 40 pemphigus cases (30 pemphigus vulgaris and 10 pemphigus foliaceus) and 37 non-pemphigus cases (35 vesiculobullous skin diseases and 2 normal skin). Skin biopsy was obtained for histopathological diagnosis, immunofluorescence study, and immune-histochemical studying for IgG4 and C3d expression. IgG4 was positive in almost all cases of pemphigus vulgaris and most of pemphigus foliaceus and bullous pemphigoides, while all other diseases were negative. C3d expression was positive in almost all bullous pemphigoides and pemphigus gestationis cases, while it was negative in almost all other cases. Sensitivity and specificity of both markers increase by using them in combination in diagnosis of such bullous diseases. IgG4 and C3d immunohistochemistry could replace DIF in almost all of our cases, so before doing DIF, reliable immunohistochemical detection of IgG4 and C3d on formalin-fixed tissue is advised to be done.

Conceptualization and validation of an innovative direct immunofluorescence technique utilizing fluorescein conjugate against IgG + IgG4 for routinely diagnosing autoimmune bullous dermatoses

“…IgG4 antibodies predominate in both active PF and active PV [ 12 , 21 , 27 , 28 ]. In contrast, in paraneoplastic pemphigus (PNP) the autoantibodies mainly belong to IgG1 and IgG2 subclasses [ 2 , 13 , 29 ]. The analysis of the subclass distribution of IgG antibodies in the skin of patients with BP by DIF microscopy revealed IgG4 as being the prevailing subclass, followed by IgG1 autoantibodies, while IgG2 and IgG3 autoantibodies were found only occasionally [ 27 , 30 ].…”

“…However, this finding is not sufficient to support its significant involvement in pathogenesis of blister formation in pemphigus diseases [ 36 ]. Complement protein C3 plays an important role in activation of the complement system in classical, lectin and alternative pathways [ 13 , 37 ]. In animal models using complement-deficient mice, different complement pathways are involved in the pathogenesis of different ABDs [ 37 ].…”

“…It is known that IgG is the most abundant isotype in the human serum, constituting about 80% of the total serum immunoglobulin [ 12 ]. There are four IgG subclasses in humans numbered 1 to 4 in the order of their discovery and serum concentration [ 13 ]. IgG1, the most abundant subclass, is present in serum in the range 5-11 mg/ml, whereas IgG4, the least abundant one, is present in concentration of 0.35-0.51 mg/ml [ 13 , 14 ].…”

“…There are four IgG subclasses in humans numbered 1 to 4 in the order of their discovery and serum concentration [ 13 ]. IgG1, the most abundant subclass, is present in serum in the range 5-11 mg/ml, whereas IgG4, the least abundant one, is present in concentration of 0.35-0.51 mg/ml [ 13 , 14 ]. IgG4 is a very odd and dynamic antibody.…”

Analyses of the clinical and immunological characteristics of patients with lupus erythematosus

“…Many researchers have shown that immunohistochemical (IHC) detection of C3d and C4d deposition in skin biopsy specimens is of great diagnostic value when evaluating some inflammatory skin diseases, such as bullous pemphigoid and pemphigoid gestationis. [ 5 6 7 ] Several studies[ 8 ] have established the role of immunohistochemical deposits of C3d and C4d along the basement membrane zone (BMZ) in the diagnosis of patients with LE.…”