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Connective tissue diseases and related disorders

Impaired expression of innate immunity-related genes in IgG4-related disease: A possible mechanism in the pathogenesis of IgG4-RD

Takuji NakamuraDepartment of Rheumatology and Immunology, Nagahama City Hospital, Shiga, Japan; ;Hematology and Immunology, Kanazawa Medical University, Ishikawa, Japan; Correspondence[email protected]

Tomomi Satoh-NakamuraDepartment of Rheumatology and Immunology, Nagahama City Hospital, Shiga, Japan; ;Hematology and Immunology, Kanazawa Medical University, Ishikawa, Japan;

Akio NakajimaHematology and Immunology, Kanazawa Medical University, Ishikawa, Japan; ;Division of Rheumatology, Kudo General Hospital, Ishikawa, Japan;

Takafumi KawanamiHematology and Immunology, Kanazawa Medical University, Ishikawa, Japan;

Tomoyuki SakaiHematology and Immunology, Kanazawa Medical University, Ishikawa, Japan;

Yoshimasa FujitaHematology and Immunology, Kanazawa Medical University, Ishikawa, Japan;

Haruka IwaoHematology and Immunology, Kanazawa Medical University, Ishikawa, Japan;

Miyuki MikiHematology and Immunology, Kanazawa Medical University, Ishikawa, Japan;

Yasufumi MasakiHematology and Immunology, Kanazawa Medical University, Ishikawa, Japan;

Toshiro OkazakiHematology and Immunology, Kanazawa Medical University, Ishikawa, Japan;

Yasuhito IshigakiMedical Research Institute, Kanazawa Medical University, Ishikawa, Japan;

Mitsuhiro KawanoDivision of Rheumatology, Department of Internal Medicine, Kanazawa University Hospital, Ishikawa, Japan;

Kazunori YamadaDivision of Rheumatology, Department of Internal Medicine, Kanazawa University Hospital, Ishikawa, Japan;

Shoko MatsuiHealth Administration Center, University of Toyama, Toyama, Japan;

Takako SaekiDepartment of Internal Medicine, Nagaoka Red Cross Hospital, Niigata, Japan;

Terumi KamisawaDepartment of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan;

Motohisa YamamotoDepartment of Rheumatology, Sapporo Medical University School of Medicine, Hokkaido, Japan;

Hideaki HamanoMedical Informatics Division and Department of Internal Medicine, Gastroenterology, Shinshu University School Hospital, Nagano, Japan;

Tomoki OriguchiFirst Department of Internal Medicine, Department of Immunology and Rheumatology, Nagasaki Graduate School of Health Sciences, Nagasaki, Japan;

Shintaro HirataThe First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Fukuoka, Japan; ;Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan;

Yoshiya TanakaThe First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Fukuoka, Japan;

Hiroto TsuboiDepartment of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan;

Takayuki SumidaDepartment of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan;

Kazuichi OkazakiThird Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan;

Masao TanakaHematology and Immunology, Kanazawa Medical University, Ishikawa, Japan; ;Department of Clinical Immunology, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Kyoto, Japan;

Tsutomu ChibaDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Tsuneyo MimoriDepartment of Clinical Immunology, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Kyoto, Japan;

Hisanori UmeharaDepartment of Rheumatology and Immunology, Nagahama City Hospital, Shiga, Japan; ;Hematology and Immunology, Kanazawa Medical University, Ishikawa, Japan; Correspondence[email protected]

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Abstract

Background: IgG4-related disease (IgG4-RD) is characterized by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells. The pathogenesis of this disease is not clear. Transcriptome analysis was performed to identify genes over- and under-expressed in patients with IgG4-RD.

Method: DNA microarray analysis was performed using RNA from peripheral blood mononuclear cells of two patients with IgG4-RD and four healthy individuals. Genes showing a greater than threefold change in expression in IgG4-RD patients following steroid therapy were identified. Four genes related to innate immunity such as transcobalamin I (TCN1), secretory leukocyte peptidase inhibitor (SLPI), bactericidal/permeability-increasing protein (BPI) and lactotransferrin (LTF) were assessed by real-time PCR in 15 IgG4-RD patients and 13 healthy individuals.

Result: DNA microarray analysis identified 30 genes showing a greater than threefold change in expression in IgG4-RD patients following steroid therapy. Real-time RT-PCR showed that the levels of mRNAs encoding TCNI and SLPI, except for BPI and LTF, were significantly lower in patients with IgG4-RD than in healthy people. The levels of all four mRNAs in patients with IgG4-RD were significantly increased after steroid treatment.

Conclusion: These results indicate that reduction in expression of innate immunity-related genes may participate in the pathogenesis of IgG4-RD that steroid treatment may rectify impaired innate immunity as well as acquired immunity.

Keywords:

Author contributions

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published.

Dr. Umehara had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study conception and design: Nakamura, Satoh-Nakamura, Nakajima, Kawanami, Umehara. Acquisition of data: Sakai, Fujita, Iwao, Miki, Masaki, Okazaki, Yamada, Matsui, Saeki, Kamisawa, Yamamoto, Hamano, Origuchi, Hirata, Tanaka, Tsuboi, Sumida, Tanaka.

Analysis and interpretation of data: Ishigaki, Kawano, Okazaki, Chiba, Mimori, Umehara.

Conflict of interest

None.

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Impaired expression of innate immunity-related genes in IgG4-related disease: A possible mechanism in the pathogenesis of IgG4-RD

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Impaired expression of innate immunity-related genes in IgG4-related disease: A possible mechanism in the pathogenesis of IgG4-RD

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