A common major histocompatibility complex class II allele HLA-DQB1* 0301 is present in clinical variants of pemphigoid.

Abstract

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease seen primarily in elderly persons. It is characterized clinically by the development of tense bullae and by the presence of an antibasement membrane antibody. In BP, the antigens involved in the autoimmunity are epidermal basement membrane peptides BPAgl and BPAg2. We have compared high resolution typing of major histocompatibility complex class II loci (HLA-DRB1, DQB1) in 21 patients with BP, 17 with ocular cicatricial pemphigoid (OCP), and 22 with oral pemphigoid (OP) to a panel of 218 haplotypes of normal individuals. We found that the three diseases (BP, OCP, and OP) have significant association with DQB1*0301 (P = 0.005, P < 0.0001, and P = 0.001, respectively). The frequencies of alleles DQB1*0302, *0303, and *06, which share a specific amino acid sequence from position 71 to 77 (Thr-Arg-Ala-Glu-Leu-Val-Thr) were also increased (P = 0.01). We suggest that an identical major histocompatibility complex class II allele (DQB1*0301) is a common marker for enhanced susceptibility and that the same amino acid residues in positions 71-77 (DQB1*0301, -0302, -0305, -0602, -0603 alleles) are found in patients with BP, OCP, and OP. Our findings propose that the autoimmune response in the three different clinical variants of pemphigoid, involves the recognition by T cells of a class II region of DQB1, bound to a peptide from the basement membrane of conjunctiva, oral mucosa, and skin.Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease seen primarily in elderly persons and is characterized clinically by the development of blisters. Therapy usually involves oral corticoids and frequently immunosuppressant agents (1). There is in vivo deposition of immunoglobulins (Ig) and complement components at the basement membrane zone of the dermo-epidermal junction. Sera of the majority of patients contains anti-basement membrane zone autoantibodies (1).It is postulated that the lesions in BP result from autoimmunization with IgG class autoantibodies against antigens BPAgl and BPAg2, components of the epidermal basement membrane zone (2). Recently, it has been demonstrated that passive transfer of autoantibodies that recognize BPAg2, when injected into neonatal mice, can produce clinical BP (3).In previous studies we have shown an association between the DQB1*0301 allele with ocular cicatricial pemphigoid (OCP) and oral pemphigoid (OP), when compared with a population of normal controls (4, 5). While in patients with pemphigus vulgaris we have found an association with HLA-DR4, DQ8 among Jewish patients, and DR6, DQ5 in nonJewish patients (6-8).In the present report, 21 Caucasian patients with BP were studied for major histocompatibility complex (MHC) class II DRB1, DQB1 alleles, using amplification of genomic DNA by the polymerase chain reaction and sequence-specific oligonucleotide probe hybridization. Frequencies were compared with 218 haplotypes of normal individuals. MATERIALS AND METHODSTwenty-one patients with BP were typed ...

Localized Bullous Pemphigoid on the Site of Knee Arthroplasty: A Case Report

“…As for genetic factors of BP, the strongest association has been documented for human leukocyte antigen DQ1*0301 which was observed in 90% of patients with BP in one of the fi rst studies that tackled this matter (12). Among triggering factors which can be identifi ed in only 15% of cases (2), several diff erent factors have been implied, such as drug intake (i.e.…”

Identification and characterization of autoreactive T cell responses to bullous pemphigoid antigen 2 in patients and healthy controls.

“…10 of 12 BPAG2-reactive HLA-typed BP patients carried the HLA class II allele DQB1*0301 which has been shown to be prevalent in BP (20). Strikingly, eight healthy carriers of DQB1*0301 also showed T cell responses to BPAG2 whereas PBMC from 14 normal patients carrying HLA class II alleles other than DQB1*0301 were not stimulated by BPAG2.…”

Autoreactive T and B Cells from Bullous Pemphigoid (BP) Patients Recognize Epitopes Clustered in Distinct Regions of BP180 and BP230

“…Autoreactive Th cells that recognize regions of the BP180 ECD, including the immunodominant NC16A region, have been described in selected patients with BP and Pg (23)(24)(25)(26)(27). Clinically, BP has been associated with several MHC class II alleles, HLA-DQB1*0301, -*0305, -*0602, and -*0603 (28). HLA-DQB1*0301, in particular, has been linked to IgG autoantibody production in patients with MMP (29).…”