¹Interstitial Lung Disease Unit, Imperial College at the National Heart and Lung Institute, Emmanuel Kaye Building, Manresa Road, London SW3 6LR, UK

²Royal Free Academic Department of Rheumatology and Connective Tissue Disease, The Royal Free Hospital, Row land Hill Street, London NW3 2PF, UK

Correspondence to: Prof.R M du Bois, Interstitial Lung Disease Unit, Emmanuel Kaye Building, Manresa Road, London SW3 6LR, UK. E-mail r.dubois@rbh.nthames.nhs.uk

This work was supported by the Raynaud's and Scleroderma Association, UK.

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. Genes and Immunity (2001) 2 , 76-81.

systemic sclerosis; pulmonary fibrosis; anti-topoisomerase; anti-centromere; MHC; autoantibodies