44274 Direct immunofluorescence IgG autoantibody subclass analysis as a tool to differentiate between bullous systemic lupus erythematosus and epidermolysis bullosa acquisita

Bullous systemic lupus erythematosus (BSLE) and epidermolysis bullosa acquisita (EBA) are immunobullous disorders caused by antibodies against type-VII collagen. Histologic presentations are identical, with subepidermal blisters and neutrophilic infiltrates in the dermis. Direct immunofluorescent staining (DIF) shows linear depositions of IgG and C3 and uncommonly IgM/IgA along the dermo- epidermal junction (DEJ). Salt-split skin shows dermal deposition of immunoglobulins. Clinically, they present with erythematous dermal plaques, and tense vesicles/bullae involving the face, trunk, and extensor extremities. Clinico-histopathologic differentiation may be difficult as 30-50% of BSLE precede SLE and EBA can present with systemic symptoms of fever, non-erosive arthritis and be associated with SLE. Western-blot of serum IgG subclasses have shown elevated IgG2/IgG3 and IgG1/IgG4 in BSLE and EBA, respectively. DIF of IgG subclasses in perilesional skin may aid in the differentiation between BSLE and EBA. We report 4 patients with clinico-histopathologic differential diagnoses of BSLE or EBA. Frozen tissue-slides from perilesional skin was obtained from each patient. Primary rabbit anti-human monoclonal antibodies against IgG1/IgG2/IgG3/IgG4 were added to the tissue and then incubated with goat anti-rabbit antibodies conjugated with Alexa-Fluor-488. Images were captured via Olympus microscope 10x and 20x magnification. Two people blinded to the study evaluated the intensity of the DIF staining. At the DEJ, DIF showed stronger linear IgG2 and IgG3 staining in BSLE, whereas EBA showed stronger linear IgG1 and IgG4 staining. In cases with features consistent with both BSLE and EBA, IgG subclass analysis via DIF, can be useful to prioritize diagnostic options and to decide therapeutic management.