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STRONG ASSOCIATION OF SEVERE PULMONARY SARCOIDOSIS WITH HLA DQB1*0602.
Ella M. van den Berg-Loonen, Prof Dr, Christina E.M. Voorter, Dr and Marjolein Drent, Dr. University Hospital Maastricht Tissue Typing Laboratory and Maastricht Netherlands, 6229 HX, Dep of Respiratory Medicine.

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Sarcoidosis is a granulomatous disease that has been reported to be associated with different HLA alleles. We studied 149 dutch caucasian sarcoidosis patients and 624 controls. Patients were classified having mild (chest X-ray stage I;n=39) or severe (stage II,III or IV;n=110) pulmonary sarcoidosis. Patients and controls were typed for class I (A, B) by serology and for class II by molecular methods. Genes DRB1,3,4,5 and DQB1 were typed at a low resolution level (PCR-SSP), while DQB1 and DPB1 were also typed at high resolution level by SBT.
The DQB1 gene showed the strongest association with the disease. At low resolution level a moderate increase was shown for DQB1*06 and a slight decrease for DQB1*05 and *02. At high resolution level the increase of DQB1*06 proved to be present in only one of seven subtypes detected, DQB1*0602 (pc<0.001). The increase was most clear in patients with severe disease course. The decrease of DQB1*05 and *02 was not significant for any of the subtypes. Most genes in the HLA region (except DPB1) are strongly linked, for that reason deviant frequencies in one gene usually affect the frequencies of alleles in other genes. For DRB1 an increase was noticed for the DQB1*06 associated DRB1*15 allele while DRB1*01 showed a decrease (pc<0.01). Since DRB5 is in linkage disequilibrium with DRB1*15, an increase was also found for DRB5. No significant differences were noticed for DPB1 frequencies between patients and controls.
DQB1*0602 is strongly associated with sarcoidosis in our patients showing an increase in both mild and severe disease course, but more pronounced in the latter. The linked HLA alleles DRB1*15 and DRB5 are also increased, probably secondary to the increase of DRB1*0602.