HLA-DQB10602* allele is associated with splenomegaly in Japanese sarcoidosis

Authors: Sato, H.¹; Nagai, S.; du Bois, R. M.¹; Handa, T.²; Suginoshita, Y.³; Ohta, K.⁴; Welsh, K. I.¹; Izumi, T.⁴

Source: Journal of Internal Medicine, Volume 262, Number 4, October 2007 , pp. 449-457(9)

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Abstract:

. Sato H, Nagai S, du Bois RM, Handa T, Suginoshita Y, Ohta K, Welsh KI, Izumi T (Imperial College of Science, Technology & Medicine, London, UK; Kyoto University; Central Clinic in Kyoto; and Kyoto University, Kyoto; Japan). HLA-DQB1*0602 allele is associated with splenomegaly in Japanese sarcoidosis. J Intern Med 2007; J Intern Med 2007; 262: 449-457. Objectives.

The association between HLA class II alleles and susceptibility to sarcoidosis is well documented. Further, the HLA-DRB1*15 and DQB1*0602 haplotype has been considered as a marker for both chronic and severe disease. Splenomegaly has been proposed as a marker for severity and activity in sarcoidosis, although its functional mechanism is unknown. In other diseases, HLA class II alleles can be markers for splenomegaly. We therefore set out to test the hypothesis that the primary DRB1*15-DQB1*0602 link in sarcoidosis would be to splenomegaly. Design and subjects.

We performed abdominal ultrasonography to evaluate the prevalence and extent of splenomegaly and genotyped for HLA-DRB1 and DQB1 using allele or allele group specific primers in polymerase-chain-reaction on 138 Japanese sarcoidosis patients as case comparison study. Furthermore, we explored their relationship with other clinically important indices, e.g. chest radiograph stage, serum angiotensin-converting enzyme (ACE) concentration and duration of disease. Results.

Splenomegaly was detected in 37 (26.8%) sarcoidosis patients. DQB1*0602 showed associations with splenomegaly (P < 0.0001) and longer disease duration (P = 0.007). In addition, higher chest radiograph staging was associated with both DQB1*0602 (P = 0.02) and splenomegaly (P = 0.003). The presence of splenomegaly was associated with higher serum ACE concentration (P < 0.0001). Conclusion.

We conclude that in the Japanese population the primary association of HLA class II DQB1*0602 is with splenomegaly. This allele is also a marker for chronicity and lung disease severity. On the other hand, the presence of splenomegaly is a marker for severity and activity. Further studies are needed to explore the relationship between splenomegaly and sarcoidosis in other ethnic groups and its association with HLA-DQB1*0602.

Keywords: genetic; HLA class II; sarcoidosis; splenomegaly

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2796.2007.01829.x

Affiliations: 1: From the Interstitial Lung Disease Unit, Royal Brompton Hospital and NHLI, Imperial College of Science, Technology & Medicine, London, UK 2: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan 3: Department of Gastroenterology, Graduate School of Medicine Kyoto University, Kyoto, Japan 4: Central Clinic in Kyoto, Kyoto, Japan

Publication date: 2007-10-01