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      Association of serum levels of antibodies against MMP1, CBX1, and CBX5 with transient ischemic attack and cerebral infarction

      research-article
      1 , 2 , 1 , 1 , 3 , 1 , 3 , 1 , 3 , 3 , 1 , 4 , 5 , 6 , 7 , 8 , 9 , 9 , 1 , 4 , 4 , 4 , 4 , 1 , 10 , 10 , 10 , 10 , 10 , 11 , 11 , 11 , 11 , 11 , 12 , 13 , 12 , 12 , 13 , 12 , 12 , 6 , 14 , 15 , 16 , 16 , 1 , 1 , 1 , 1 , 1 , 1 , 1
      Oncotarget
      Impact Journals LLC
      TIA, cerebral infarction, SEREX, antibody biomarker, atherosclerosis, Gerotarget

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          Abstract

          Transient ischemic attack (TIA) is a predictor for cerebral infarction (CI), and early diagnosis of TIA is extremely important for the prevention of CI. We set out to identify novel antibody biomarkers for TIA and CI, and detected matrix metalloproteinase 1 (MMP1), chromobox homolog 1 (CBX1), and chromobox homolog 5 (CBX5) as candidate antigens using serological identification of antigens by recombinant cDNA expression cloning (SEREX) and Western blotting to confirm the presence of serum antibodies against the antigens. Amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) revealed that serum antibody levels were significantly higher in patients with TIA or acute-phase CI (aCI) compared with healthy donors ( P < 0.01). Spearman’s correlation analysis and multivariate logistic regression analysis demonstrated that levels of anti-MMP1, anti-CBX1, and anti-CBX5 antibodies were associated with age, cigarette-smoking habits, and blood pressure. Thus, serum levels of antibodies against MMP1, CBX1, and CBX5 could potentially serve as useful tools for diagnosing TIA and predicting the onset of aCI.

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          Most cited references46

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          A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening.

          Serological analysis of recombinant cDNA expression libraries (SEREX) using tumor mRNA and autologous patient serum provides a powerful approach to identify immunogenic tumor antigens. We have applied this methodology to a case of esophageal squamous cell carcinoma and identified several candidate tumor targets. One of these, NY-ESO-1, showed restricted mRNA expression in normal tissues, with high-level mRNA expression found only in testis and ovary tissues. Reverse transcription-PCR analysis showed NY-ESO-1 mRNA expression in a variable proportion of a wide array of human cancers, including melanoma, breast cancer, bladder cancer, prostate cancer, and hepatocellular carcinoma. NY-ESO-1 encodes a putative protein of Mr 17,995 having no homology with any known protein. The pattern of NY-ESO-1 expression indicates that it belongs to an expanding family of immunogenic testicular antigens that are aberrantly expressed in human cancers in a lineage-nonspecific fashion. These antigens, initially detected by either cytotoxic T cells (MAGE, BAGE, GAGE-1) or antibodies [HOM-MEL-40(SSX2), NY-ESO-1], represent a pool of antigenic targets for cancer vaccination.
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            Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase.

            The pancreatic islet beta-cell autoantigen of relative molecular mass 64,000 (64K), which is a major target of autoantibodies associated with the development of insulin-dependent diabetes mellitus (IDDM) has been identified as glutamic acid decarboxylase, the biosynthesizing enzyme of the inhibitory neurotransmitter GABA (gamma-aminobutyric acid). Pancreatic beta cells and a subpopulation of central nervous system neurons express high levels of this enzyme. Autoantibodies against glutamic acid decarboxylase with a higher titre and increased epitope recognition compared with those usually associated with IDDM are found in stiff-man syndrome, a rare neurological disorder characterized by a high coincidence with IDDM.
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              Human neoplasms elicit multiple specific immune responses in the autologous host.

              Expression of cDNA libraries from human melanoma, renal cancer, astrocytoma, and Hodgkin disease in Escherichia coli and screening for clones reactive with high-titer IgG antibodies in autologous patient serum lead to the discovery of at least four antigens with a restricted expression pattern in each tumor. Besides antigens known to elicit T-cell responses, such as MAGE-1 and tyrosinase, numerous additional antigens that were overexpressed or specifically expressed in tumors of the same type were identified. Sequence analyses suggest that many of these molecules, besides being the target of a specific immune response, might be of relevance for tumor growth. Antibodies to a given antigen were usually confined to patients with the same tumor type. The unexpected frequency of human tumor antigens, which can be readily defined at the molecular level by the serological analysis of autologous tumor cDNA expression cloning, indicates that human neoplasms elicit multiple specific immune responses in the autologous host and provides diagnostic and therapeutic approaches to human cancer.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                19 January 2018
                31 December 2017
                : 9
                : 5
                : 5600-5613
                Affiliations
                1 Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba, Japan
                2 Department of Anesthesia, The First Affiliated Hospital, Jinan University, Guangzhou, P. R. China
                3 Medical Project Division, Research Development Center, Fujikura Kasei Co., Saitama, Japan
                4 Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
                5 Department of Neurological Surgery, Chiba Prefectural Sawara Hospital, Chiba, Japan
                6 Department of Neurosurgery, Chiba Cerebral and Cardiovascular Center, Chiba, Japan
                7 Department of Neurology, Chiba Rosai Hospital, Chiba, Japan
                8 Department of Neurology, Chibaken Saiseikai Narashino Hospital, Chiba, Japan
                9 Department of Internal Medicine, Chiba Aoba Municipal Hospital, Chiba, Japan
                10 Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan
                11 Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
                12 Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
                13 Department of Pharmacology, Shiga University of Medical Science, Shiga, Japan
                14 Port Square Kashiwado Clinic, Kashiwado Memorial Foundation, Chiba, Japan
                15 Department of Neurology, Kashiwado Hospital, Chiba, Japan
                16 Department of Surgery, School of Medicine, Toho University, Tokyo, Japan
                Author notes
                Correspondence to: Takaki Hiwasa, hiwasa_takaki@ 123456faculty.chiba-u.jp
                Article
                23789
                10.18632/oncotarget.23789
                5814161
                29464021
                aec6b28d-789c-49f4-8b0f-0b8fb2439d66
                Copyright: © 2018 Wang et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 12 August 2017
                : 16 November 2017
                Categories
                Research Paper: Gerotarget (Focus on Aging)

                Oncology & Radiotherapy
                tia,cerebral infarction,serex,antibody biomarker,atherosclerosis,gerotarget
                Oncology & Radiotherapy
                tia, cerebral infarction, serex, antibody biomarker, atherosclerosis, gerotarget

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