Serum IFN-γ levels predict the therapeutic effect of mesenchymal stem cell transplantation in active rheumatoid arthritis
Authors: Wei Guo
Rongseng Zhao
Wei Xing
Chongyang Liu
Xiao He
Xiang Xu
Dongpo Jiang
Yi Yang
Ming Zhu
Journal: Journal of Translational Medicine (2018)
Discipline: CLINICAL MEDICINE
Keywords: Clinical trial; IFN-γ; Mesenchymal stem cell; Rheumatoid arthritis.
Affiliations: First Department, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, 400042, People's Republic of China., Department of Rheumatology and Clinical Immunology, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, 400042, People's Republic of China., Department of Critical Care Medicine, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, 400042, People's Republic of China., Department of Rheumatology and Clinical Immunology, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, 400042, People's Republic of China. ., First Department, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, 400042, People's Republic of China. .

Abstract:  Background: To explore the mechanism of the different clinical efficacies of mesenchymal stem cell transplantation (MSCT) and identify a possible serum biomarker for predicting the therapeutic effect of MSCT in rheumatoid arthritis (RA) patients. Methods: A total of 105 patients with persistently active RA and poor responses to traditional medication were randomly divided into MSCT and control groups. Outcomes were evaluated according to the 28-joint Disease Activity Score and Health Assessment Questionnaire, serological indicators, regulatory T cell (Treg) to T helper 17 (Th17) cell ratio, and inflammatory cytokine levels. Twelve weeks after MSCT, the outcomes of the MSCT group were evaluated according to the European League against Rheumatism response criteria. Patients with a good or moderate response were added to the response group, and those with no response were added to the no-response group. Results: No serious adverse events were reported for either MSCT subgroup (28 in the response group and 24 in the no-response group). The therapeutic effects lasted for 48 weeks without continuous administration. Notably, a transient increase in serum IFN-γ (&gt;2 pg/ml) levels was observed in the response group, but not in the no-response group. Furthermore, an increase in IL-10 levels and the Treg/Th17 ratio and a reduction in IL-6 levels appeared 2-3 weeks after the transient IFN-γ increase. Conclusions: Allogeneic MSCT is safe and feasible, and we propose high serum IFN-γ levels as a potent biomarker for predicting MSCT response. Trial registration chictr.org, ChiCTR-ONC-16008770. Registered 3 July 2016, http://www.chictr.org.cn/showproj.aspx?proj=14820. 

Retracted: No

PubPeer comments:
  Influenza A virus was injected to the mice through intravenous to induce the COPD model It is not immediately clear to me why infecting Sprague-Dawley mice with Influenza A (which strain?) by intravenous injection (not intra-nasal?) should result in chronic obstructive pulmonary disease. There do not seem to be many published precedents for this supposed murine model of COPD. ,