Autoantibody Profile of a Cohort of 54 Italian Patients with Linear IgA Bullous Dermatosis: LAD-1 Denoted as a Major Auto-antigen of the Lamina Lucida Subtype

Abstract

Linear IgA bullous dermatosis (LABD) is characterized by presence of multiple IgA autoantibodies, and a comparatively lesser number of IgG antibodies, directed against different hemidesmosomal antigens. The main autoantigens are LAD-1, LABD-97, BP180 and BP230, type VII collagen and laminin 332. We retrospectively studied the serology of 54 Italian patients with LABD using enzyme-linked immunosorbent assay (ELISA), immunoblotting assay, and indirect immunofluorescence on monkey oesophagus and salt-split skin. Among these, indirect immunofluorescence of salt-split skin elicits the greatest sensitivity. Sixty-three percent of the sera were observed to be positive, with a lamina lucida pattern observed in 48%, a sub-lamina densa pattern in 2% and a mixed pattern in 13% of the cases. IgA reactivity to LAD-1 on immunoblotting was found in 52% of sera, to BP180-NC16A by ELISA in 32% and to BP230 in 26%. Only 17% of patients possessed circulating IgG autoantibodies. LAD-1 was determined to be a major autoantigen of the lamina lucida subtype. Combined serological assays demonstrated a high sensitivity (82%), suggesting that this approach could support diagnosis when a biopsy is not feasible or direct immunofluorescence results are negative.

Keywords: BP180; BP230; LAD-1; diagnostic sensitivity; humoral immune response; linear IgA bullous disease.

Fig. 1

(A) Schematic representation of human BP180 and its fragments LAD-1 and linear IgA bullous dermatosis (LABD)-97. (B) The shed ectodomain of BP180 (LAD-1) is recognized by IgG and IgA autoantibodies as a 120-kDa polypeptide. Anti-BP180-positive bullous pemphigoid serum bind 120-kDa polypeptide by IgG (lane 1), molecular weight marker (lane 2), an anti-BP180 positive LABD serum bind 120-kDa polypeptide by IgA (lane 3), healthy volunteer serum does not bind 120-kDa polypeptide by IgA (lane 4); (C) IgA reactivity to LAD-1 (120 kDa) detected by immunoblotting: lane 1, healthy volunteer serum; lane 2, LABD control serum; lanes 3–7, LABD patient sera from the present study.