Th17/IL-17A axis is critical for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc): SSc patients with high levels of serum IL-17A exhibit reduced lung functions and increased prevalence of PAH

Background: It is thought that systemic sclerosis (SSc) might be a T helper 17 (Th17) cell -driven autoimmune disease. Noticeably, pulmonary arterial hypertension (PAH) is a leading cause of death in patients with SSc. Here, we investigated the association between serum Th17-related cytokines and prevalence of PAH in SSc patients. Methods: This study included 72 SSc patients and 51 healthy controls (HC). We determined clinical manifestations, immunophenotypes including Th subsets in peripheral blood lymphocytes, and the serum levels of interleukin (IL) -17A, IL-17A/F, IL -17B. IL -17C, IL -17D. IL-1 beta, IL -6, IL -21, IL -22, and IL -23. Results: The frequency of Th17 cells was significantly increased in SSc patients compared to HC and was positively correlated with the modified Rodnan skin scores. Furthermore, the serum levels of IL -17A, IL -17D, IL-1 beta, and IL -6 were significantly increased in SSc patients compared to HC. SSc patients with detected IL -17A showed high levels of IL-17A/F, IL-1 beta, IL -6, and IL -22, and high frequency of Th17 cells. Interestingly, these patients exhibited the reduced lung functions and increased prevalence of PAH significantly compared to patients with undetected IL -17A. Similarly, SSc patients with detected IL -17A and high IL -6 (>= 1.2 pg/mL) exhibited the decreased lung functions and increased prevalence of PAH compared to patients with undetected IL -17A and low IL -6. Conclusion: We found that SSc patients with high levels of serum IL -17A or both IL -17A and IL -6 show reduced lung functions and high prevalence of PAH. Consequently, it is highly probable that Th17/IL-17A axis is critical for the prevalence of PAH in SSc patients.