HLA-DR2 predicts susceptibility and disease chronicity in Irish sarcoidosis patients.
BACKGROUND
HLA-DR2 (15) and 14 (6) have been recently proposed as susceptibility alleles for the development of sarcoidosis and HLA-DR15 as a marker of poor outcome, but validation in other populations is necessary.


METHODS
Employing serological techniques, we HLA-typed 103 Irish sarcoidosis patients and 105 ethnically-matched healthy controls for class I A and B and II DR and DQ alleles.


RESULTS
HLA-B5 (10% vs. 2%, p = 0.018) and DR2 (45% vs. 27%, p = 0.007) were positively associated and B15 (0% vs. 7%, p = 0.01) negatively associated with sarcoidosis compared to control subjects. Seventy-five patients were followed > 2 years and 47 (63%) had chronic and 28 (37%) non-chronic disease. HLA-DR2 (55% vs. 27%, p = 0.001) and DR11 (26% vs. 5%, p<0.0001) were significantly more frequent in chronic disease vs. controls, in contrast to HLA-DR3 (13% vs. 38%, p = 0.002), which had a significant negative association. HLA-B5 (11% vs. 2%, p = 0.029) and DR3 (64% vs. 38%, p = 0.005) were significantly more frequent in non-chronic disease. Of the 29 patients achieving spontaneous remission, 24 (83%) were HLA-DR3 -positive and DR3-positivity was associated with significantly greater carbon monoxide diffusion at follow-up compared to DR3-negative patients (90% vs. 82% predicted, p = 0.027).


CONCLUSIONS
This study supports the role of HLA-DR2 (15) as both a susceptibility and poor prognostic marker in sarcoidosis and DR2 positive patients may particularly benefit from close follow-up and early treatment. In contrast, DR3 positive patients are at a much lesser risk of chronic disease. Studies for long-term treatment effects require stratification for HLA-DR2 and DR3 status.
Rutherford
Robert M
RM
Department of Respiratory Medicine, Merlin Park Regional Hospital, Galway, Ireland. robert.rutherford@northumbria-healthcare.nhs.uk
Brutsche
Martin H
MH
Kearns
Miriam
M
Bourke
Mary
M
Stevens
Fiona
F
Gilmartin
John J
JJ
D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D002248:Carbon Monoxide / Q000097:blood; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D005500:Follow-Up Studies; D015802:HLA-DR2 Antigen / Q000032:analysis* / Q000494:pharmacology*; D006801:Humans; D007494:Ireland; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012075:Remission, Spontaneous; D012307:Risk Factors; D012507:Sarcoidosis / Q000276:immunology* / Q000473:pathology*
D015415:Biomarkers; D015802:HLA-DR2 Antigen; D002248:Carbon Monoxide