title: Elevated Neopterin Levels Are Associated with Increased Tuberculosis Risk in Rheumatoid Arthritis Patients with QuantiFERON Conversion during Biologic Therapy.
abstract: QuantiFERON-TB-Gold (QFT-G) conversion is frequently observed in rheumatoid arthritis (RA) patients receiving biologic therapy. However, there have not been any known biomarkers available for detecting tuberculosis (TB) in QFT-G converters. We aimed to evaluate clinical utility of cytokines/chemokines for detecting TB in patients with QFT-G conversion. Among a total of 227 RA patients who underwent QFT-G assay, 187 QFT-G-negative patients received biologic therapy without isoniazid prophylaxis. QFT-G assay was repeated at week 52 of biologic therapy or at the time of TB diagnosis. Levels of cytokines/chemokines were determined by magnetic bead array or ELISA in QFT-G converters and 12 non-RA patients with TB (non-RA TB). QFT-G conversion was found in 54 (28.9%) of 187 baseline QFT-G-negative patients, of which 7 (13.0%) developed active TB during the one-year follow-up period. Among the examined cytokines/chemokines, non-stimulated and TB-antigen-stimulated neopterin levels were significantly higher in RA patients who developed TB (RA-TB) (median, 24.5pg/ml and 23053pg/ml, respectively) and non-RA TB patients (12.2pg/ml and 9633pg/ml, respectively) compared with QFT-G converters without TB (3.0pg/ml and 2720pg/ml, respectively, both p<0.001). Rising levels of neopterin relative to baseline (non-stimulated levels, 4.4pg/ml vs. 24.5pg/ml; TB-antigen-stimulated levels, 1801pg/ml vs. 23053pg/ml) were observed in QFT-G converters who developed TB. A high proportion (85.7%) of QFT-G converters with high plasma neopterin levels developed TB during the one-year follow-up period. In conclusion, RA patients with QFT-G conversion during the period of biologic therapy should be carefully monitored for elevation of neopterin levels, which is associated with TB risk in QFT-G converters, particularly in TB-endemic areas.
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Medical Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan.|Faculty of Medicine, National Yang Ming University, Taipei, Taiwan.|Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.|Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Der-Yuan
authors.initials: DY
authors.lastname: Chen
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine, China Medical University Hospital, Taichung, Taiwan.|College of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Ju-Pi
authors.initials: JP
authors.lastname: Li
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Medical Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan.|Faculty of Medicine, National Yang Ming University, Taipei, Taiwan.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Tsai-Ling
authors.initials: TL
authors.lastname: Liao
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Medical Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan.|Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Hsin-Hua
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Medical Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan.|Faculty of Medicine, National Yang Ming University, Taipei, Taiwan.
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Hsieh
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Medical Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Yea-Wen
authors.initials: YW
authors.lastname: Yeh
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine, China Medical University Hospital, Taichung, Taiwan.|College of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Joung-Liang
authors.initials: JL
authors.lastname: Lan
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000150:complications* / Q000188:drug therapy; D015415:Biomarkers; D015897:Comorbidity; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D005260:Female; D006801:Humans; D059425:Interferon-gamma Release Tests; D055985:Latent Tuberculosis / Q000150:complications / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood*; D011379:Prognosis; D012306:Risk; D014376:Tuberculosis / Q000150:complications* / Q000175:diagnosis*
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D016207:Cytokines; D019798:Neopterin