Investigation of novel biomarkers for predicting the clinical course in patients with ulcerative colitis
Shinsaku Hamanaka
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorCorresponding Author
Tomoo Nakagawa
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Correspondence
Dr Tomoo Nakagawa, Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chiba City, Chiba 260-8670, Japan.
Email: [email protected]
Search for more papers by this authorTakaki Hiwasa
Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorYuki Ohta
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorShingo Kasamatsu
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorHideaki Ishigami
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorTakashi Taida
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorKenichiro Okimoto
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorKeiko Saito
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorDaisuke Maruoka
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorTomoaki Matsumura
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorHirotaka Takizawa
Port Square Kashiwado Clinic, Kashiwado Memorial Foundation, Chiba City, Chiba, Japan
Search for more papers by this authorKoichi Kashiwado
Department of Neurology, Kashiwado Hospital, Chiba City, Chiba, Japan
Search for more papers by this authorSohei Kobayashi
Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorKazuyuki Matsushita
Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorHisahiro Matsubara
Department of Academic Surgery, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorTatsuro Katsuno
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorMakoto Arai
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorNaoya Kato
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorShinsaku Hamanaka
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorCorresponding Author
Tomoo Nakagawa
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Correspondence
Dr Tomoo Nakagawa, Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chiba City, Chiba 260-8670, Japan.
Email: [email protected]
Search for more papers by this authorTakaki Hiwasa
Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorYuki Ohta
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorShingo Kasamatsu
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorHideaki Ishigami
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorTakashi Taida
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorKenichiro Okimoto
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorKeiko Saito
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorDaisuke Maruoka
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorTomoaki Matsumura
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorHirotaka Takizawa
Port Square Kashiwado Clinic, Kashiwado Memorial Foundation, Chiba City, Chiba, Japan
Search for more papers by this authorKoichi Kashiwado
Department of Neurology, Kashiwado Hospital, Chiba City, Chiba, Japan
Search for more papers by this authorSohei Kobayashi
Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorKazuyuki Matsushita
Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorHisahiro Matsubara
Department of Academic Surgery, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorTatsuro Katsuno
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorMakoto Arai
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorNaoya Kato
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan
Search for more papers by this authorAbstract
Background
The clinical course of ulcerative colitis (UC) is characterized by repeated episodes of relapse and remission. We hypothesized that biomarkers that help distinguish refractory UC patients who are in remission using strong anti-immunotherapy could contribute in preventing the overuse of corticosteroids for treatment. Here, we clarified novel autoantibodies for UC patients in remission as clinical indicators to distinguish between refractory and non-refractory UC.
Methods
Antigen proteins recognized by serum antibodies of patients with UC in remission were screened using the protein array method. To validate the results, AlphaLISA was used to analyze the serum antibody titers with candidate protein antigens. Serum samples from 101 healthy controls, 121 patients with UC, and 39 patients with Crohn's disease were analyzed.
Results
Of 66 candidate protein antigens screened by ProtoArray™, six were selected for this study. The serum titers of anti-poly ADP-ribose glycohydrolase (PARG), anti-transcription elongation factor A protein-like 1, and anti-proline-rich 13 (PRR13) antibodies were significantly higher in patients with UC than in healthy controls. Anti-PARG and anti-PRR13 antibody titers were significantly higher in patients with refractory UC than in patients with non-refractory UC. There were no significant differences in any antibody titer between the active and remission phases.
Conclusions
The serum titers of anti-PARG, anti-transcription elongation factor A protein-like 1, and anti-PRR13 antibodies were elevated in patients with UC. Anti-PARG and anti-PRR13 antibody titers may be novel clinical indicators for detecting refractory UC in patients in remission.
Supporting Information
| Filename | Description |
|---|---|
| jgh14297-sup-0001-Sup.Fig1.tifTIFF image, 1.8 MB |
Figure S1. Algorithm to select reliable candidate antigens in this study. First, our criteria to select reliable candidate antigens were that the positivity rate in the serum of patients with ulcerative colitis (UC) was more than 60% and the positivity rate in the serum of healthy controls (HCs) was less than 20%. Second, of 66 antigens, 12 proteins were extracted by comparing the specific antigens identified in the following six disorders: Sjogren's syndrome, rheumatoid arthritis, systemic lupus erythematosus, acute inflammatory demyelinating polyneuropathy, obsessive–compulsive disorder, and atherosclerosis. The specificity of a disorder was defined as a positivity rate in the sera of patients with the disorder of more than 80% and a positivity rate in the sera of the HCs of less than 20%. Finally, 6 of 12 proteins were examined in the order of the high positivity rate in this study. |
| jgh14297-sup-0002-Sup.Fig2.tifTIFF image, 2.9 MB |
Figure S2. Comparison of reactivity to anti-Saccharomyces cerevisiae antibody (ASCA) IgG (A) and IgA (B) titers in the serum of healthy controls (HCs), patients with ulcerative colitis (UC), and patients with Crohn's disease (CD) by enzyme-linked immunosorbent assay (ELISA). The concentrations of ASCA IgG and IgA are plotted as dot diagrams with median values and interquartile ranges indicated as bars. *P < 0.05. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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