TY - JOUR
T1 - Pemphigus vulgaris in Jewish patients is associated with HLA-A region genes
T2 - Mapping by microsatellite markers
AU - Slomov, Elena
AU - Loewenthal, Ron
AU - Goldberg, Ilan
AU - Korostishevsky, Michael
AU - Brenner, Sara
AU - Gazit, Ephraim
N1 - Funding Information:
This work was supported in part by a grant from the Hirsch and Genia Wasserman Foundation (to E.G.).
PY - 2003/8/1
Y1 - 2003/8/1
N2 - Pemphigus vulgaris (PV) is the most severe autoimmune blistering disorder of the skin that is mediated by circulating autoantibodies against desmoglein 3 (Dsg3). It has been reported that in Jews the associated haplotype in PV is human leukocyte antigen (HLA) B38, DRB1*0402, DQB1*0302. Significant associations with HLA were observed also in non-Jews. Dsg3-specific T-cell responses were detected in PV patients but also in healthy individuals who were either carriers of the PV-associated DRB1*0402 allele or alleles that share similar or identical peptide binding motifs to DRB1*0402. This suggests that genes other than the classical major histocompatibility complex (MHC) genes are associated with the development of the autoimmune response. We used 16 microsatellite probes that span the entire MHC region to screen DNA samples from 38 PV patients and 76 healthy controls. Results demonstrated that some markers were associated with class II region including a TAP associated marker. However, four probes, D6S265, C_527, D6S510, and MOGC, which are all mapped to the region of HLA-A, were highly associated with PV. These results suggest that a gene, or genes in the class I region are important in the initiation of the autoimmune cascade. Activation/suppression of these genes might act as the trigger mechanism that starts the autoimmune destructive process.
AB - Pemphigus vulgaris (PV) is the most severe autoimmune blistering disorder of the skin that is mediated by circulating autoantibodies against desmoglein 3 (Dsg3). It has been reported that in Jews the associated haplotype in PV is human leukocyte antigen (HLA) B38, DRB1*0402, DQB1*0302. Significant associations with HLA were observed also in non-Jews. Dsg3-specific T-cell responses were detected in PV patients but also in healthy individuals who were either carriers of the PV-associated DRB1*0402 allele or alleles that share similar or identical peptide binding motifs to DRB1*0402. This suggests that genes other than the classical major histocompatibility complex (MHC) genes are associated with the development of the autoimmune response. We used 16 microsatellite probes that span the entire MHC region to screen DNA samples from 38 PV patients and 76 healthy controls. Results demonstrated that some markers were associated with class II region including a TAP associated marker. However, four probes, D6S265, C_527, D6S510, and MOGC, which are all mapped to the region of HLA-A, were highly associated with PV. These results suggest that a gene, or genes in the class I region are important in the initiation of the autoimmune cascade. Activation/suppression of these genes might act as the trigger mechanism that starts the autoimmune destructive process.
KW - Autoimmunity
KW - Desmoglein
KW - Disease
KW - HLA
KW - Microsatellite
KW - Pemphigus vulgaris
UR - http://www.scopus.com/inward/record.url?scp=0042209917&partnerID=8YFLogxK
U2 - 10.1016/S0198-8859(03)00092-2
DO - 10.1016/S0198-8859(03)00092-2
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AN - SCOPUS:0042209917
VL - 64
SP - 771
EP - 779
JO - Human Immunology
JF - Human Immunology
SN - 0198-8859
IS - 8
ER -
