Çocukluk çağında ailesel Akdeniz ateşi ve eşlik eden spondiloartritte enflamatuvar belirteçlerin değerlendirilmesi

Abstract

Familial Mediterranean fever (FMF) is a hereditary disease characterized by recurring, self-limited inflammatory episodes. The disease is caused by a gain-of-function mutation in MEFV (MEditerranean FeVer) gene, encoding pyrin protein, the key element of the pyrin inflammasome, resulting in excessive production of proinflammatory cytokines, namely IL-1β, IL-6 and IL-18. Innate immunity was thought to be the sole perpetrator in the chronic inflammation, however, contemporary research provided evidence of the role of adaptive immunity in inflammatory process. Spondyloarthropathies accompanying FMF consist of inflammatory arthritides, sacroiliitis, spondylitis, enthesitis and extraskeletal manifestations, in children classified as enthesitis relared arthritis (ERA). The pathogenesis of these conditions is unclear, however the common perception is that antigen-specific immune response with underlying chronic inflammation is the causative mechanism. In this study, chosen inflammatory marker levels are evaluated in order to gain further knowledge on the pathogenetic mechanisms of FMF and acompanying spondyloarthritis (SpA). Thus, we recruited the patients whose routine examinations were in between December 2020 and June 2021, creating four groups with FMF-SpA with high disease activity, ERA with high disease activity, FMF during attack period and FMF remission period. Having collected 20 samples, the inflammatory marker levels of these groups are compared with each disease group and the healthy donors. IL-18 levels are statistically significantly increased in FMF-SpA group, suggesting the chance to be an inflammatory biomarker for ERA/spondyloarthritides in the FMF group. TNF-α levels are increased in all the disease groups compared to healthy controls are statistically significant. This increment is validating the anti-TNF-α agents in the treatment of both FMF and ERA. The fact that IFN-α2 levels were unmeasurably low in the high disease activity groups in contrast to the healthy donors and FMF remission groups strengthens the theory of no type 1 IFN activity in these inflammatory pathways. Lastly, MCP-1 levels are significantly low in all the patient groups compared with the healthy controls. This study is the first to investigate the inflammatory pathogenesis of FMF and accompanying SpA in children and the fact that most of the inflammatory marker levels are comparable among the disease groups indicates that these entities share a common inflammatory pathway. Corroboratory studies are needed to further evaluate the role of these cytokines and their incorporation into personalized medicine.