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Class IIHLA associations with autoantibodies in scleroderma: a highly significant role for HLA-DP

Gilchrist, FC; Bunn, C; Foley, PJ; Lympany, PA; Black, CM; Welsh, KI; du Bois, RM; (2001) Class IIHLA associations with autoantibodies in scleroderma: a highly significant role for HLA-DP. Genes and Immunity , 2 (2) 76 - 81.

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Abstract

Scleroderma is a condition of variable phenotype characterised by fibrosis of the skin and internal organs. There is a range of disease-specific autoantibodies found in the sera of patients. The aims of this study were to: (1) investigate the role of the MHC and particularly HLA-DP in the production of autoantibodies; (2) investigate clinical associations with autoantibodies. We have performed HLA class II typing using PCR with sequence-specific primers on DNA samples from 202 scleroderma patients and 307 UK control subjects. All patients had well defined clinical phenotypes. Sera from patients were examined for the presence of disease specific autoantibodies in particular the anti-topoisomerase autoantibody (ATA), the anti- centromere autoantibody (ACA) and the anti-RNA polymerase autoantibody (ARA). There was a striking association between HLA-DPB1*1301 and ATA (P-corr = 0.0001). In addition, ATA was associated with HLA- DRB1*11 and the anticentromere autoantibody (ACA) with HLA-DRB1*04, HLA-DRB1*08 (P = 0.001) and HLA-DQB1 alleles with a glycine residue at position 26. Very strong associations were detected between clinical phenotypes and autoantibodies. ATA was associated with pulmonary fibrosis (P = 0.00002), anti-RNA polymerase autoantibody (ARA) with renal involvement (P = 0.0000006) and diffuse skin disease (P = 0.00001), and ACA with limited skin involvement (P = 0.00002) and protection against pulmonary fibrosis (P = 0.0000003). We have identified a significant association between the ATA and HLA-DPB1*1301 which may provide an insight into how this autoantibody is formed. Patient clinical characteristics depend on the autoantibodies they carry

Type:Article
Title:Class IIHLA associations with autoantibodies in scleroderma: a highly significant role for HLA-DP
Additional information:Journal English Article NATURE PUBLISHING GROUP APR 421GH BASINGSTOKE GENES IMMUN HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND
Keywords:Allele, Alleles, ANTIGEN, Antigens, Association, ASSOCIATIONS, Autoantibodies, Blood, Case-Control Studies, Caucasoid Race, characteristics, Class, Class II, clinical, CLINICAL CHARACTERISTICS, Condition, control, disease, DNA, DNA Topoisomerases, Type I, DNA-Directed RNA Polymerase, EC, Fibrosis, Genes, MHC Class II, genetics, Genotype, Glycine, Great Britain, heart, HLA, HLA-DP Antigens, HLA-DPB1, IM, immunology, INSIGHT, internal, INVOLVEMENT, LA, Lung, May, Methods, MHC, Patient, patients, PCR, Phenotype, phenotypes, physiopathology, polymerase, Polymerase Chain Reaction, POSITION, PRIMERS, production, PROTECTION, pulmonary, Pulmonary Fibrosis, RANGE, renal, Rna, Role, SAMPLE, SAMPLES, SCLERODERMA, Scleroderma, Systemic, SERA, serum, Skin, Support, Non-U.S.Gov't, UK, variable, anti-centromere, anti-topoisomerase, ANTINUCLEAR ANTIBODIES, Centromere, DNA TOPOISOMERASE-I, English, GENE, HLA-DPB1 ALLELES, HLA-DQB1 1ST DOMAIN, Major Histocompatibility Complex, nature, PCR-SSP, PROGRESSIVE SYSTEMIC-SCLEROSIS, Publishing, RNA-POLYMERASES, SEQUENCE-SPECIFIC PRIMERS, SYSTEMIC SCLEROSIS, T-CELL, Tissue
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)

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