Sato H, Nagai S, du Bois R M, Handa T, Suginoshita Y, Ohta K, Welsh K I, Izumi T
Interstitial Lung Disease Unit, Royal Brompton Hospital and NHLI, Imperial College of Science, Technology & Medicine, London, UK.
J Intern Med. 2007 Oct;262(4):449-57. doi: 10.1111/j.1365-2796.2007.01829.x.
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.
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.
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).
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.
HLA Ⅱ类等位基因与结节病易感性之间的关联已有充分记录。此外，HLA-DRB1 15和DQB1 0602单倍型被认为是慢性和严重疾病的标志物。脾肿大已被提议作为结节病严重程度和活动度的标志物，尽管其功能机制尚不清楚。在其他疾病中，HLA Ⅱ类等位基因可作为脾肿大的标志物。因此，我们着手检验以下假设：结节病中主要的DRB1 15-DQB1 0602关联与脾肿大有关。
作为病例对照研究，我们对138例日本结节病患者进行了腹部超声检查，以评估脾肿大的患病率和程度，并使用聚合酶链反应中的等位基因或等位基因组特异性引物对HLA-DRB1和DQB1进行基因分型。此外，我们还探讨了它们与其他临床重要指标的关系，如胸部X线分期、血清血管紧张素转换酶（ACE）浓度和病程。
在37例（26.8%）结节病患者中检测到脾肿大。DQB1 0602与脾肿大（P<0.0001）和较长病程（P = 0.007）相关。此外，较高的胸部X线分期与DQB1 0602（P = 0.02）和脾肿大（P = 0.003）均相关。脾肿大的存在与较高的血清ACE浓度相关（P<0.0001）。
我们得出结论，在日本人群中，HLA Ⅱ类DQB1 0602的主要关联与脾肿大有关。该等位基因也是慢性和肺部疾病严重程度的标志物。另一方面，脾肿大的存在是严重程度和活动度的标志物。需要进一步研究以探讨其他种族中脾肿大与结节病之间的关系及其与HLA-DQB1 0602的关联。
