Common ancestral origin of pemphigus vulgaris in Jews and Spaniards: a study using microsatellite markers

Abstract

Pemphigus is a group of autoimmune blistering diseases of the skin and mucous membranes. The association of pemphigus with human leukocyte antigen (HLA) is widely accepted. It was described in many ethnic groups and in most countries of the world. Studies showed that the associated HLA haplotype in Jewish pemphigus vulgaris (PV) patients is HLA-B38, DRB1*0402, and DQB1*0302; or HLA-B35, DRB1*0402, and DQB1*0302. Similar associations with class II genes were found in Spanish non-Jewish PV patients. As Jews lived in Spain for hundreds of years and many converted to Christianity, the presence of the same HLA haplotype in the Jewish and Spanish PV suggests that they may share the same founder. Microsatellite markers which span the entire major histocompatibility complex (MHC) locus were used as genetic probes. They were utilized to dissect the MHC region in the search for possible common haplotypes, besides HLA, which may provide an answer to this question. It was found that in both cohorts, in addition to HLA class II genes, there are probably genes in the class I region which are associated with PV. Alleles belonging to the associated markers were used to construct haplotypes and to estimate genetic distances. The distance between the two PV cohorts is relatively short, but the distance between the Jewish patients and the Jewish controls is greater compared to the distance between Spanish patients and Spanish controls. In both PV populations, the same microsatellite haplotypes in addition to a common class II haplotype were found, suggesting that both patient populations originated from the same genetic stock and, therefore, share the same ancestral disease gene.

Frequency analysis of HLA class I alleles in Iranian patients with progressive and non-progressive chronic lymphocytic leukemia

“…A similar finding was also reported by others [20], though controversial results have also been published [16,21,22,25,33]. An increased frequency of the HLA-B35 allele has also been reported in some other malignancies and autoimmune diseases from different ethnic populations, including Hodgkin's lymphoma [34], autoimmune thyroiditis [35], autoimmune hepatitis [36] autoimmune arthritis [37], Moyamoya [38], and pemphigus vulgaris [39], suggesting a critical correlation of this allele with hematologic malignancies and other pathologic conditions.…”

Immunohistological analysis of immune cells in blistering skin lesions

“…In this respect, the presence of CD68+ macrophages is essential for uptake, processing and presentation of the antigenic epitopes associated with the major histocompatibility complex class II to the CD3+ T cells. [41][42][43][44][45] The increased density of CD3+ cells may be due to: (1) increased antigenicity of the lesional cells; (2) production of soluble factors (chemokines) 17 19 23 46 ; (3) increased expression of adhesion molecules 35 47 48 ; and (4) increased tissue accessibility for immune cells. Several antigens were reported in the bullous skin lesions, such as bullous pemphigoid antigen 2 (bullous pemphigoid), 49 130-kDa polypeptide pemphigus vulgaris 29 and cutaneous lymphocyte-associated antigen.…”

A review of case–control studies on the risk factors for the development of autoimmune blistering diseases

“…13 A third and rare subtype, PNP, shares an association with certain malignancies and presents with severe blistering of oral and conjunctival surfaces. 16,17 On the other hand, PF has been associated with certain desmoglein 1 polymorphisms. 15 The age of onset of pemphigus is variable, but peaks between 60 and 70 years.…”