Class II HLA associations with autoantibodies in scleroderma: a highly significant role for HLA-DP
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...
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| Veröffentlicht in: | Genes and immunity 2001-04, Vol.2 (2), p.76-81 |
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| creator | Gilchrist, F C Bunn, C Foley, P J Lympany, P A Black, C M Welsh, K I du Bois, R M |
| description | 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 (Pcorr = 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. |
| doi_str_mv | 10.1038/sj.gene.6363734 |
| format | Article |
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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 (Pcorr = 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.</description><identifier>ISSN: 1466-4879</identifier><identifier>EISSN: 1476-5470</identifier><identifier>DOI: 10.1038/sj.gene.6363734</identifier><identifier>PMID: 11393660</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Antigens ; Autoantibodies ; Autoantibodies - blood ; Case-Control Studies ; DNA Topoisomerases, Type I - immunology ; DNA-directed RNA polymerase ; DNA-Directed RNA Polymerases - immunology ; Drb1 protein ; European Continental Ancestry Group ; Fibrosis ; Genes, MHC Class II ; Genotype ; Histocompatibility antigen HLA ; histocompatibility locus HLA ; HLA-DP Antigens - genetics ; HLA-DP beta-Chains ; Humans ; Lung diseases ; Major histocompatibility complex ; Nucleotide sequence ; Patients ; Phenotype ; Phenotypes ; Polymerase Chain Reaction - methods ; Pulmonary fibrosis ; Pulmonary hypertension ; RNA polymerase ; Scleroderma ; Scleroderma, Systemic - genetics ; Scleroderma, Systemic - immunology ; Scleroderma, Systemic - physiopathology ; Skin diseases ; Tissue typing ; United Kingdom</subject><ispartof>Genes and immunity, 2001-04, Vol.2 (2), p.76-81</ispartof><rights>Copyright Nature Publishing Group Apr 2001</rights><rights>Macmillan Publishers Limited 2001.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c294t-145d61ba9f29f2f89248e59a25a7f52c6c390e87b6147311bec52445919934343</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11393660$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gilchrist, F C</creatorcontrib><creatorcontrib>Bunn, C</creatorcontrib><creatorcontrib>Foley, P J</creatorcontrib><creatorcontrib>Lympany, P A</creatorcontrib><creatorcontrib>Black, C M</creatorcontrib><creatorcontrib>Welsh, K I</creatorcontrib><creatorcontrib>du Bois, R M</creatorcontrib><title>Class II HLA associations with autoantibodies in scleroderma: a highly significant role for HLA-DP</title><title>Genes and immunity</title><addtitle>Genes Immun</addtitle><description>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 (Pcorr = 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.</description><subject>Antigens</subject><subject>Autoantibodies</subject><subject>Autoantibodies - blood</subject><subject>Case-Control Studies</subject><subject>DNA Topoisomerases, Type I - immunology</subject><subject>DNA-directed RNA polymerase</subject><subject>DNA-Directed RNA Polymerases - immunology</subject><subject>Drb1 protein</subject><subject>European Continental Ancestry Group</subject><subject>Fibrosis</subject><subject>Genes, MHC Class II</subject><subject>Genotype</subject><subject>Histocompatibility antigen HLA</subject><subject>histocompatibility locus HLA</subject><subject>HLA-DP Antigens - genetics</subject><subject>HLA-DP beta-Chains</subject><subject>Humans</subject><subject>Lung diseases</subject><subject>Major histocompatibility complex</subject><subject>Nucleotide sequence</subject><subject>Patients</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Polymerase Chain Reaction - methods</subject><subject>Pulmonary fibrosis</subject><subject>Pulmonary hypertension</subject><subject>RNA polymerase</subject><subject>Scleroderma</subject><subject>Scleroderma, Systemic - genetics</subject><subject>Scleroderma, Systemic - immunology</subject><subject>Scleroderma, Systemic - physiopathology</subject><subject>Skin diseases</subject><subject>Tissue typing</subject><subject>United Kingdom</subject><issn>1466-4879</issn><issn>1476-5470</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkc1rGzEQxUVJaT7ac29BJJDb2prVd2_GbRKDoT20Z6GVtbbMepVKuwT_99USQyEQwgzMO_zmweMh9BXIDAhV87yfbX3vZ4IKKin7gC6ASVFxJsnZpIWomJL6HF3mvCcEBAj9CZ0DUE2FIBeoWXY2Z7xa4cf1AhcZXbBDiH3Gz2HYYTsO0fZDaOIm-IxDj7PrfIobnw72G7Z4F7a77ohz2PahDa6wOMXO4zamybL6_usz-tjaLvsvp3uF_tz_-L18rNY_H1bLxbpytWZDBYxvBDRWt3XZVumaKc-1rbmVLa-dcFQTr2QjSkQK0HjHa8a4Bq0pK3OF7l58n1L8O_o8mEPIzned7X0cs5FEE0mIfBcEBYQoqgp4-wrcxzH1JYSpBQNZc8JpoW7epEApobScrOYvkEsx5-Rb85TCwaajAWKmKk3em6lKc6qyfFyfbMfm4Df_-VN39B_9NZe0</recordid><startdate>200104</startdate><enddate>200104</enddate><creator>Gilchrist, F C</creator><creator>Bunn, C</creator><creator>Foley, P J</creator><creator>Lympany, P A</creator><creator>Black, C M</creator><creator>Welsh, K I</creator><creator>du Bois, R M</creator><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200104</creationdate><title>Class II HLA associations with autoantibodies in scleroderma: a highly significant role for HLA-DP</title><author>Gilchrist, F C ; Bunn, C ; Foley, P J ; Lympany, P A ; Black, C M ; Welsh, K I ; du Bois, R M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c294t-145d61ba9f29f2f89248e59a25a7f52c6c390e87b6147311bec52445919934343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Antigens</topic><topic>Autoantibodies</topic><topic>Autoantibodies - 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Academic</collection><jtitle>Genes and immunity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gilchrist, F C</au><au>Bunn, C</au><au>Foley, P J</au><au>Lympany, P A</au><au>Black, C M</au><au>Welsh, K I</au><au>du Bois, R M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Class II HLA associations with autoantibodies in scleroderma: a highly significant role for HLA-DP</atitle><jtitle>Genes and immunity</jtitle><addtitle>Genes Immun</addtitle><date>2001-04</date><risdate>2001</risdate><volume>2</volume><issue>2</issue><spage>76</spage><epage>81</epage><pages>76-81</pages><issn>1466-4879</issn><eissn>1476-5470</eissn><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 (Pcorr = 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.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>11393660</pmid><doi>10.1038/sj.gene.6363734</doi><tpages>6</tpages></addata></record> |
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| subjects | Antigens Autoantibodies Autoantibodies - blood Case-Control Studies DNA Topoisomerases, Type I - immunology DNA-directed RNA polymerase DNA-Directed RNA Polymerases - immunology Drb1 protein European Continental Ancestry Group Fibrosis Genes, MHC Class II Genotype Histocompatibility antigen HLA histocompatibility locus HLA HLA-DP Antigens - genetics HLA-DP beta-Chains Humans Lung diseases Major histocompatibility complex Nucleotide sequence Patients Phenotype Phenotypes Polymerase Chain Reaction - methods Pulmonary fibrosis Pulmonary hypertension RNA polymerase Scleroderma Scleroderma, Systemic - genetics Scleroderma, Systemic - immunology Scleroderma, Systemic - physiopathology Skin diseases Tissue typing United Kingdom |
| title | Class II HLA associations with autoantibodies in scleroderma: a highly significant role for HLA-DP |
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