Takateru Izumi

HLA‐DQB1*0602 allele is associated with splenomegaly in Japanese sarcoidosis

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.

Chymase Gene (CMA1) Polymorphisms in Dutch and Japanese Sarcoidosis Patients

Background: Chymase is released from mast cells following activation. Evidence suggests that chymase plays an important role in tissue injury and remodeling of the lungs, heart and skin. Objective: We postulated that chymase gene (CMA1) polymorphisms are associated with pulmonary fibrosis in Dutch and with cardiac and skin involvement in Japanese sarcoidosis patients. Patients and Methods: Dutch (n = 153) and Japanese (n = 122) sarcoidosis patients with controls (Dutch, n = 309; Japanese, n = 111) were studied. Pulmonary involvement in Dutch patients as well as clinical manifestations in Japanese patients was evaluated for association with five CMA1 polymorphisms. Results: The CMA1 polymorphisms were not associated with disease susceptibility in either population, or with radiographic evolution in the Dutch or with cardiac or skin involvement in the Japanese patients. The –526 T allele was associated with a lower iVC in Dutch patients. Conclusions: The CMA1 polymorphisms studied do not contribute to disease susceptibility in Japanese or Dutch sarcoidosis patients. CMA1 polymorphisms do not influence radiographic evolution in Dutch sarcoidosis patients, nor do they predispose to cardiac or skin involvement in Japanese patients. However, the association between CMA1 –526 C/T and iVC in the Dutch patients suggests that chymase may modify the functional outcome of pulmonary sarcoidosis.

Treatment with Methotrexate in Patients with Sarcoidosis

Sarcoidosis is a systemic inflammatory disease of unknown etiology. The hallmark histological feature of the disease is epithelioid cell granuloma derived from activated T cells and macro‐ phages triggered by unknown immune stimuli such as bacterial protein or beryllium metal [1, 2]. Various inflammatory cytokines and growth factors can participate in the pathophysiolog‐ ical processes of sarcoidosis [1].

Pulmonary Angiitis and Granulomatosis

Sarcoidosis is characterized pathologically by non-caseating epithelioid cell granulomas in multiple organs; however, its etiology remains unknown. Although intrathoracic lesions are detected in almost all cases of sarcoidosis, pulmonary symptoms infrequently lead to the detection of patients. Sarcoidosis is more often found by chest radiographs, which are obtained during medical checkups, or because of symptoms of the skin and eyes. Extrathoracic lesions which cause certain symptoms are often detected in the eyes, the skin, the central nerves and the peripheral nerves. Although granulomatous lesions are histologically known to frequently form in the liver, lesions in the liver rarely cause symptoms.