Sindrome infiammatoria multisistemica: caratteristiche genetiche e cliniche in pazienti pediatrici del Medio Oriente

Abstract

Multisystem inflammatory syndrome: genetic and clinical characteristics in middle east pediatric patients Clinical, genetic and laboratory characteristics of Middle Eastern patients with Multisystem Inflammatory Syndrome in children (MIS-C) are not yet defined, this cohort study of 45 patients affected by MIS-C, mainly of Arab and of Asian origin, allows to define the genetic contribution to this disease. In the patients analyzed, a concentration of rare and probably pathogenic genetic variants of immune-related genes was found, and a possible association between genetic results, onset of MIS-C and resistance to treatment was also scored. Significant dysregulation of inflammatory markers was found in all patients analyzed, while mucocutaneous and gastrointestinal manifestations were found in 36 patients (80%), cardiac alterations in 22 (48.9%), neurological manifestations in 14 (31.1%). Genetic alterations in immune-related genes, including TLR3, TLR6, IL22RA2, IFNB1, and IFNA6, were identified in 19 patients (42.2%), with a significant difference with the control group (29 vs 3, P = <0.001). Patients with these variants tend to have an earlier onset of disease than controls (7 patients [36.8%] with genetic variants were 3 years younger at onset than 2 patients [7.7%] without genetic variants) and more resistance to treatment (8 patients [42.1%] with genetic variants who received 2 doses of intravenous immunoglobulins, compared to 3 patients [11.5%] with no evidence of genetic variants). The results of the study suggest that rare and probably deleterious genetic variants may play a role in MIS-C. This paves the way for further studies on larger and more diverse populations to fully characterize the contribution of genetics to this novel pathological entity.