MHC Regulation of Immune Responses

Hameed, A.; Ahmed, A. Razzaque

doi:10.1016/s0733-8635(18)30238-9

Dermatologic Clinics

1993

DOI: 10.1016/s0733-8635(18)30238-9

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MHC Regulation of Immune Responses

A. Hameed

A. Razzaque Ahmed

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Cited by 3 publications

(2 citation statements)

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“…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.…”

mentioning

confidence: 99%

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

Delgado

Turbay

Yunis

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

194

117

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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 ...

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mentioning

confidence: 99%

“…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).…”

mentioning

confidence: 99%

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

Delgado

Turbay

Yunis

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

194

117

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Diseases of the oral mucous membranes

Camisa

Rindler

1996

Current Problems in Dermatology

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HLA-DRB104 and DRB114 Alleles Are Associated with Susceptibility to Pemphigus Among Japanese

Miyagawa

Higashimine

Iida

et al. 1997

Journal of Investigative Dermatology

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It has previously been demonstrated that susceptibility to pemphigus vulgaris is associated with human leukocyte antigen (HLA)-DR4 serologic specificity among Ashkenase Jews, and with DR4 as well as DR6 (DR14) in other ethnic groups. We genotyped HLA-DRB1, DQA1, DQB1, and DPB1 alleles in 16 patients with pemphigus by polymerase chain reaction-restriction fragment length polymorphism, to find evidence of potential HLA class II allele associations with pemphigus in Japanese patients who have a relatively homogeneous ethnic background. All nine patients with pemphigus vulgaris and five of seven patients with pemphigus foliaceus carried one or two alleles of HLA-DRB1*04 (*0403, *0406) and HLA-DRB1*14 (*1401, *1405, *1406) subtypes. Sequence analysis of these DRB1*04 and DRB1*14 alleles revealed the amino acid homology of phenylalanine at position 26 and valine at position 86 with the DRB1*0402 allele that reportedly confers a strong susceptibility to pemphigus vulgaris in Ashkenazi Jews. Thus our findings, together with previous HLA studies on pemphigus vulgaris patients of different ethnic groups, suggest that HLA-DRB1*04 and DRB1*14 alleles are commonly associated with pemphigus vulgaris across racial barriers. These HLA-DRB1 alleles are likely to be also associated with pemphigus foliaceus. Further studies on more diverse ethnic populations will be helpful in determining the significance of the association between certain amino acid residues of the class II molecules and disease susceptibility to pemphigus vulgaris as well as pemphigus foliaceus.

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MHC Regulation of Immune Responses

Cited by 3 publications

References 44 publications

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

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

Diseases of the oral mucous membranes

HLA-DRB104 and DRB114 Alleles Are Associated with Susceptibility to Pemphigus Among Japanese

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MHC Regulation of Immune Responses

Cited by 3 publications

References 44 publications

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

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

Diseases of the oral mucous membranes

HLA-DRB1*04 and DRB1*14 Alleles Are Associated with Susceptibility to Pemphigus Among Japanese

Contact Info

Product

Resources

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HLA-DRB104 and DRB114 Alleles Are Associated with Susceptibility to Pemphigus Among Japanese