JMJD6 Autoantibodies as a Potential Biomarker for Inflammation-Related Diseases

Author:

Zhang Bo-Shi12ORCID,Zhang Xiao-Meng2,Ito Masaaki3,Yajima Satoshi4,Yoshida Kimihiko4,Ohno Mikiko56,Nishi Eiichiro56,Wang Hao2ORCID,Li Shu-Yang12,Kubota Masaaki17,Yoshida Yoichi17,Matsutani Tomoo1,Mine Seiichiro189,Machida Toshio1910,Takemoto Minoru1112,Yamagata Hiroki12,Hayashi Aiko11,Yokote Koutaro11,Kobayashi Yoshio13,Takizawa Hirotaka14,Kuroda Hideyuki15,Shimada Hideaki34,Iwadate Yasuo1,Hiwasa Takaki1237

Affiliation:

1. Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan

2. Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan

3. Department of Clinical Oncology, Graduate School of Medicine, Toho University, Tokyo 143-8541, Japan

4. Department of Gastroenterological Surgery, Graduate School of Medicine, Toho University, Tokyo 143-8541, Japan

5. Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan

6. Department of Pharmacology, Shiga University of Medical Science, Otsu 520-2192, Japan

7. Comprehensive Stroke Center, Chiba University Hospital, Chiba 260-8677, Japan

8. Department of Neurological Surgery, Chiba Prefectural Sawara Hospital, Chiba 287-0003, Japan

9. Department of Neurological Surgery, Chiba Cerebral and Cardiovascular Center, Chiba 290-0512, Japan

10. Department of Neurosurgery, Eastern Chiba Medical Center, Chiba 283-8686, Japan

11. Department of Endocrinology, Hematology and Gerontology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan

12. Department of Diabetes, Metabolism and Endocrinology, School of Medicine, International University of Health and Welfare, Chiba 286-8686, Japan

13. Department of Cardiovascular Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan

14. Port Square Kashiwado Clinic, Kashiwado Memorial Foundation, Chiba 260-0025, Japan

15. Medical Project Division, Research Development Center, Fujikura Kasei Co., Saitama 340-0203, Japan

Abstract

Inflammation is closely associated with cerebrovascular diseases, cardiovascular diseases, diabetes, and cancers, and it is accompanied by the development of autoantibodies in the early stage of inflammation-related diseases. Hence, it is meaningful to discover novel antibody biomarkers targeting inflammation-related diseases. In this study, Jumonji C-domain-containing 6 (JMJD6) was identified by the serological identification of antigens through recombinant cDNA expression cloning. In particular, JMJD6 is an antigen recognized in serum IgG from patients with unstable angina pectoris (a cardiovascular disease). Then, the serum antibody levels were examined using an amplified luminescent proximity homogeneous assay-linked immunosorbent assay and a purified recombinant JMJD6 protein as an antigen. We observed elevated levels of serum anti-JMJD6 antibodies (s-JMJD6-Abs) in patients with inflammation-related diseases such as ischemic stroke, acute myocardial infarction (AMI), diabetes mellitus (DM), and cancers (including esophageal cancer, EC; gastric cancer; lung cancer; and mammary cancer), compared with the levels in healthy donors. The s-JMJD6-Ab levels were closely associated with some inflammation indicators, such as C-reactive protein and intima–media thickness (an atherosclerosis index). A better postoperative survival status of patients with EC was observed in the JMJD6-Ab-positive group than in the negative group. An immunohistochemical analysis showed that JMJD6 was highly expressed in the inflamed mucosa of esophageal tissues, esophageal carcinoma tissues, and atherosclerotic plaques. Hence, JMJD6 autoantibodies may reflect inflammation, thereby serving as a potential biomarker for diagnosing specific inflammation-related diseases, including stroke, AMI, DM, and cancers, and for prediction of the prognosis in patients with EC.

Funder

Japan Science and Technology Agency

JSPS KAKENHI

Publisher

MDPI AG

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