Semaphorin 5A as a Novel Diagnostic Biomarker of Juvenile Idiopathic Arthritis

Although juvenile idiopathic arthritis (JIA) is the most common form of autoimmune-driven arthritis in pediatric population, due to the lack of universal diagnostic markers and heterogeneity of the disease, many patients face a significant delay when establishing the diagnosis. As the hallmark of JIA is the inflammation of synovial membrane with pathological angiogenesis, this study aimed to compare the concentrations of semaphorin 5A (SEMA5A), protein involved in both angiogenesis and immune response, between new-onset JIA and healthy controls. Thirty-five JIA patients and 35 sex-and-age matched healthy controls were enrolled in this study. Serum concentrations of SEMA5A and vascular endothelial growth factor A (VEGF-A) were established using the enzyme-linked immunosorbent assay (ELISA) method. The serum concentration of SEMA5A was elevated in JIA patients in comparison to healthy controls with the median value of 2.04 (interquartile range [IQR]: 12.41) in JIA patients and 1.34 (IQR: 1.79) in healthy controls (<i>p</i> = 0.002). The difference was particularly prominent in oligoarticular JIA, where median SEMA5A concentration equaled 1.76 ng/mL (IQR: 1.56) in comparison to 0.33 ng/mL (IQR: 1.34) in sex-and-age-matched healthy controls (<i>p</i> = 0.001). SEMA5A concentration correlated strongly with VEGF-A concentration (<i>r</i> = 0.807, <i>p</i> < 0.001) and differed significantly in subgroups of different synovial membrane power-Doppler ultrasound (PDUS) inflammatory activities (<i>p</i> = 0.018). Although our findings need to be repeated on larger groups of JIA patients, SEMA5A is a promising marker of JIA, linked to pathological angiogenesis of synovial membrane in this entity. Moreover, it may be useful as a target of innovative treatment strategies in the nearest future.