Akio Morinobu, M.D., Ph.D. Professor
The department of Rheumatology and Clinical immunology treats patients with autoimmune diseases such as rheumatoid arthritis. The progresses of immunology research in the past have been applied clinically, and treatments in this field have made great success. However, the mechanism of autoimmunity has not yet been elucidated, and there are many new issues such as the emergence of autoimmune diseases as an aspect of cancer immunotherapy. We aim to elucidate the problems of clinical immunology using cutting edge technology of immunology, biology, and information science.
Research and EducationWe are conducting the following studies to examine etiology and pathogenesis of systemic autoimmune disease and to develop new diagnostic and therapeutic strategy for them.
1) We collected samples of 633 patients with Takayasu arteritis, and found new disease-associated genes including LILRA3 by a genomic study (Fig. 1) (Ref. 1).
2) We have screened for new autoantibodies/autoantigens in connective tissue diseases and investigated their clinical significance (Fig. 2). We conducted clinical research for therapeutic strategy of intractable diseases, such as anti-MDA5-positive interstitial lung disease with dermatomyositis (Ref. 2).
3) We have analyzed the impact of lipid mediators or their receptors/signal transduction in relation with the pathogenesis of rheumatoid arthritis (Ref. 3).
4) We have reported that human phospholipase D4 is a susceptibility gene to three autoimmune diseases. Animal study indicated that PLD4 is involved in the maintenance of immune tolerance in B cells (Ref. 4).
5) We have reported that urinary osteopontin N-half was elevated in lupus nephritis and could be a marker of diagnosis and disease activity (Ref. 5).
Fig. 1. Genes associated with Takayasu arteritis detected by GWAS
Fig. 2. Screening for autoantibodies by protein immunoprecipitation
- Terao C, Yoshifuji H, Matsumura T, et. al. Genetic determinants and an epistasis of LILRA3 and HLA-B*52 in Takayasu arteritis. Proc Natl Acad Sci U S A. 2018;115(51):13045-13050.
- Tsuji H, Nakashima R, et al. Multicenter Prospective Study of the Efficacy and Safety of Combined Immunosuppressive Therapy With High-Dose Glucocorticoid, Tacrolimus, and Cyclophosphamide in Interstitial Lung Diseases Accompanied by Anti-Melanoma Differentiation-Associated Gene 5-Positive Dermatomyositis. Arthritis Rheumatol. 2020;72(3):488-498.
- Murakami K. Potential of specialized pro-resolving lipid mediators against rheumatic diseases. Nihon Rinsho Meneki Gakkai Kaishi. 2016;39(3):155-63.
- Akizuki S, Terao C, et al. PLD4 is a genetic determinant to systemic lupus erythematosus and involved in murine autoimmune phenotypes. Ann Rheum Dis. 2019;78(4):509-518.
- Kitagori K, Yoshifuji H, et al. Cleaved Form of Osteopontin in Urine as a Clinical Marker of Lupus Nephritis. PLos One. 2016; 11(12): e0167141.
Rheumatology and Clinical ImmunologyProfessor: Akio Morinobu
Senior Lecturer: Hajime Yoshifuji
Assistant Professor: Ran Nakashima, Shuji Akizuki, Koji Kitagori, Hideaki Tsuji