HLA Haplotypes and Class II Molecular Alleles in Argentinian Patients with Pemphigus Vulgaris

Abstract

French

Background:

Pemphigus is a group of chronic blistering autoimmune diseases of which pemphigus vulgaris (PV) is the more frequent clinical form. The association of PV with the HLA serotypes suggests that there is a genetic predisposition to the disease.

Objectives:

To determine the frequency of class I and class II HLA antigens and the allelic variants of the class II HLA antigens, DR and DQ, in patients with PV and to determine the relative risk.

Methods:

An observational, prospective, transverse, and controlled study carried out between 1995 and 1999. Forty-seven patients with a diagnosis of PV and a control sampling of 199 unselected individuals from the same ethnic group were included. The HLA alleles were determined by polymerase chain reaction.

Results:

No significant associations were detected between HLA A, B, or C and our patients. The DR and DQ molecular alleles positively associated with PV were two different haplotypes: DRβ1* 0402/DQβ1* 0302 and DRβ1* 1401/DQβ1* 0503.

Conclusions:

In patients with the haplotype DRβ1* 0402/DQβ1* 0302 the affectation of 10%–30% of the corporal surface prevailed (ACS). In patients with DRβ1* 1401/DRQβ1* 0503, involvement of <10% of the ACS prevailed.

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References

Amagai

Koch

Nishikawa

. Pemphigus vulgaris antigen (desmoglein 3) is localized in the lower epidermis, the site of blister formation in patients. J Invest Dermatol 1996; 106: 351–355.

Amagai

Ishii

Takayanagui

. Transport to endoplasmic reticulum by signal peptide, but not proteolytic processing, is required for formation of conformational epitopes of pemphigus vulgaris antigen (desmoglein). J Invest Dermatol 1996; 107: 539–542.

Roh

Stanley

. Plakoglobin binding by human Dsg3 (pemphigus vulgaris antigen) in keratinocytes requires the cadherin-like intracytoplasmic segment. J Invest Dermatol 1995; 104:720–724.

Becker

Gaspari

. Pemphigus vulgaris and vegetans. Dermatol Clin 1993; 11:429–452.

Korman

. Pemphigus. J Am Acad Dermatol 1988; 18:1212–1238.

Diaz

Sampaio

Rivitti

. Endemic pemphigus foliaceus (fogo selvagem). I. Clinical features and immunpathology. J Am Acad Dermatol 1989; 20:657–669.

Diaz

Sampaio

Rivitti

. Endemic pemphigus foliaceus (fogo selvagem). II. Current and historic epidemiologic studies. J Invest Dermatol 1989; 92:4–12.

Scharf

Long

Erlich

. Sequence analysis of the HLA DRß and HLA DQß loci from three pemphigus vulgaris patients. Hum Immunol 1988; 22:61–69.

Scharf

Friedmann

Steinman

. Specific HLA DQß and HLA DRβ1 alleles confer susceptibility to pemphigus vulgaris. Proc Natl Acad Sci USA 1989; 86:6215–6219.

10.

Scharf

Friedmann

Brautbar

. HLA class II allelic variations and susceptibility to pemphigus vulgaris. Proc Natl Acad Sci USA 1988; 85:3504–3508.

11.

Sinha

Brautbar

Szafer

. A newly characterised HLA DQß allele associated with pemphigus vulgaris. Science 1989; 239:1026–1029.

12.

Szafer

Brautbar

Tzfoni

. Detection of disease specific restriction fragment length polymorphisms in pemphigus vulgaris linked to the DQw1 and DQw3 alleles of the HLA region. Proc Natl Acad Sci USA 1987; 84:6542–6545.

13.

Tussey

McMichael

. General introduction to the MHC. In: Blair

Pringle

Maudsley

, eds. Modulation of the MHC antigen expression and disease. Cambridge: Cambridge University-Press, 1995, pp 1–25.

14.

Ragoussis

. Organization of the MHC. In: Blair

Pringle

Maudsley

, eds. Modulation of the MHC antigen expression and disease. Cambridge: Cambridge University Press, 1995, pp 27–42.

15.

Glorio

Costa

G Rodriguez

Haas

. Determinación por PCR de la asociación entre antígenos HLA clase II y Pénfigo Vulgar. Medicina 1999; 59:28–32.

16.

Charron

Fauchet

. Twelfth International Histocompatibility Workshop on Reference Protocol for the HLA DNA Typing Technique, Paris, 1996.

17.

Bengtsson

Thomson

. Measuring the strength of associations between HLA antigens and diseases. Tissue Antigens 1981; 18:356.

18.

Ahmed

Park

Tiwari

. Association of DR4 with pemphigus. Exp Clin Immunogenet 1987. 4:8–16.

19.

Ahmed

Yunis

Khatri

. Major histocompatibility complex haplotype studies in Ashkenazi Jewish patients with pemphigus vulgaris. Proc Natl Acad Sci USA 1990; 87:7658–7662.

20.

Ahmed

Wagner

Khatri

. Major histocompatibility complex haplotype and class II genes in non-Jewish patients with pemphigus vulgaris. Proc Natl Acad Sci USA 1991; 88:5056–5060.

21.

Ahmed

Mohimen

Yunis

. Linkage of pemphigus vulgaris antibody to the major histocompatibility complex in healthy relatives of patients. J Exp Med 1993; 177:419–424.

22.

Nizeki

Inoko

Narimatsu

. HLA class II antigens are associated with Japanese pemphigus patients. Hum Immunol 1991; 31:246–250.

23.

Nizeki

Inoko

Mizuki

. HLA DQA1, DQB1 and DRB1 genotyping in Japanese pemphigus vulgaris patients by the PCR RFLP method. Tissue Antigens 1994; 44:248–251.

24.

Delgado

Yunis

Bozon

. MHC class alleles and haplotypes in patients with pemphigus vulgaris from India. Tissue Antigens 1996; 48:668–672.

25.

Carcassi

Cottoni

Floris

. HLA haplotypes and class II molecular alleles in Sardinian and Italian patients with pemphigus vulgaris. Tissue Antigens 1996; 48:662–667.

26.

Matzner

Erlich

Brautbar

. Identical HLA class II alleles predispose to drug triggered and idiophatic pemphigus vulgaris. Acta Derm Venereol 1995; 75:12–14.