Circulating T-Fh Cells Is Correlated With Disease Activity In Anti-Mda5 Antibody Positive Idiopathic Inflammatory Myopathies

ObjectiveIdiopathic inflammatory myopathies (IIM) are a group of disorders characterised by the production of autoantibodies and inflammatory infiltrates in the skeletal muscles. Follicular T helper (T-FH) cells are known to be crucial for B cell differentiation and autoantibody production in autoimmune diseases. The aim of this study was to investigate the involvement of T-FH cells in IIM.MethodsCirculating T(FH )cells in 44 IIM patients or 11 age- and gender-matched healthy controls (IWs) were measured by flow cytometry. ICOS, PD-1, active caspase-1 and Ki-67 expression in T-FH cells was examined. The correlations between the frequency of T-FH cells and clinical disease activities were also analysed.ResultsThe frequency of T-FH cells was 16.6% in IIM patients with anti-melanoma differentiation-associated gene (MDA5) antibody compared to 10.6% and 12.9% in anti-MDA5 negative patients or HCs, respectively (both p<0.05). The frequency of T-FH cells was positively correlated with clinical disease activities: patient/parent's assessment VAS (r=0.51, p<0.05), physician's assessment VAS (r=0.59, p<0.05) and MYOACT scores (total systems: r=0.62, p<0.05; extramuscular system: r=056, p<0.05; pulmonary system, r=055, p<0.05). The percentage of PD-(IICOShigh)-I-high T-FH cells was 3.68% in anti-MDA5 positive patients compared to 2.70% and 1.96% in anti-MDA5 negative patients or HCs, respectively (both p<0.05). The percentage of Ki-67 positive T-FH cells was 350% in anti-MDA5 positive patients compared to 236% and 1.76% in anti-MDA5 negative patients or HCs, respectively (p<0.05). Interestingly, active caspase-1 was significantly increased in T-FH cells in anti-MDA5 positive patients compared to the patients without anti-MDA5 or HCs (3.30% vs. 1.67% and 330% vs. 1.02%, both p<0.001).ConclusionThese data suggest a role for T-FH cells in the pathogenesis of anti-MDA5 positive IIM and T-FH cells might serve as a disease biomarker for this subset of patients.