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American Journal of Respiratory Cell and Molecular Biology. Vol. 27, pp. 406-412, 2002
© 2002 American Thoracic Society
DOI: 10.1165/rcmb.4782

HLA-DQB1*0201

A Marker for Good Prognosis in British and Dutch Patients with Sarcoidosis

Hiroe Sato*, Jan C. Grutters*, Panagiotis Pantelidis, A. Neil Mizzon, Tariq Ahmad, Arend-Jan van Houte, Jan-Willem J. Lammers, Jules M.M. van den Bosch, Kenneth I. Welsh and Roland M. du Bois

Clinical Genomics Group, Department of Occupational and Environmental Medicine, Imperial College of Science, Technology and Medicine, National Heart and Lung Institute, London, United Kingdom; Heart Lung Center Utrecht, Department of Pulmonology, Sint Antonius Hospital, Nieuwegein, The Netherlands; Department of Gastroenterology, Radcliffe Hospital, Oxford, United Kingdom; Department of Medical Microbiology & Immunology, Sint Antonius Hospital, Nieuwegein; and Heart Lung Center Utrecht, Department of Pulmonology, University Medical Center, Utrecht, The Netherlands

Address correspondence to: Professor R.M. du Bois, M.D., Clinical Genomics Group, National Heart and Lung Institute, 1B Manresa Road, London SW3 6LR, UK. Email: r.dubois{at}rbh.nthames.nhs.uk

Human leukocyte antigen (HLA)-DQB1 is one of the intriguing candidate genes in sarcoidosis. We performed high resolution molecular HLA-DQB1 typing on two groups of white patients (British [UK] and Dutch [NL]) in order to investigate the relationship between 19 DQB1 alleles and disease severity and progression. A total of 803 individuals were studied (133 UK and 102 NL patients, and 354 UK and 214 NL control subjects). Disease severity data included extrapulmonary disease, chest X-ray stage, lung diffusing capacity for carbon monoxide, and FVC. Progression was evaluated on follow-up chest radiographs (2 and 4 yr). The results showed DQB1*0201 to be strongly protective against severe sarcoidosis in both populations; in other words, it localized to Stage I at all time points (P < 0.0001, Pcorrected (Pc) = 0.002), whereas another DQB1 allele, *0602, tended to have opposite effects. Further, a clear association was found between the *0201 allele and Löfgren's syndrome (P < 0.0001, Pc = 0.001). More importantly, carriage of this allele reduced the risk of disease progression. In contrast, the other common split of DQB1*02, *0202, did not affect disease severity but was mildly protective against sarcoidosis in the UK population (P = 0.02, pc not significant). In conclusion, this study shows that DQB1*0201 is a strong marker for mild sarcoidosis. Additional mapping across the DQB1*0201-DRB1*0301 haplotype, including specific alleles at genes such as DRB3, tumor necrosis factor, lymphotoxin-{alpha}, I-kappa-B-like protein, and B-associated transcript 1, is necessary for a final localization of the protective effect on this haplotype.

Abbreviations: bilateral hilar lymphadenopathy, BHL • degrees of freedom, df • diffusing capacity of the lung for carbon monoxide, DLCO • erythema nodosum, EN • human leukocyte antigen, HLA • major histocompatibility complex, MHC • P values corrected for the number of DQ alleles tested, Pc • polymerase chain reaction, PCR • sequence-specific primers, SSPs




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