OBJECTIVE: To estimate the prevalence of TNFRSF11A variants in a cohort of patients with SAIDs screened for 26 related genes and describe the disease phenotypic expression.
RESULTS: A total of 12 out of 167 patients, 7 males, aged (median) 38 years at disease onset, yielded at least one TNFRSF11A rare variant. All patients carried a coexisting variant in at least one other SAID-related gene, most frequently MEFV (6 patients), but also TNFRSF1A, NOD2, NLRP3, NLRP7, MVK, IL36RN, RBCK1, PLCG2 and PSMB8. SAID episodes lasting (median) 9 days manifested with high grade fever (91%), myalgias (75%), malaise (67%), serositis (58%), arthralgias/arthritis (58%), gastrointestinal involvement (33%), and rash (25%), and responded to corticosteroids. The most common initial clinical diagnosis was TNF-associated periodic fever syndrome (TRAPS), which was, however, confirmed, in only one patient. The emergence of MEFV variations supported the diagnosis of atypical Familial Mediterranean Fever in two cases, whereas the diagnosis of Yao syndrome was speculated in two patients with NOD2 variants. The presence of atypical disease and the inability of defining diagnosis in the remaining 7 patients, supported the possible involvement of TNFRSF11A variants in the phenotypic expression of SAIDs.
CONCLUSIONS: TNFRSF11A variants, occurring in 7% of SAID patients always in combination with other SAID-related gene variants, contribute to the development of an autoinflammatory syndrome resembling to TRAPS. Additional studies to confirm novel pathogenic SAID pathways are clearly warranted.
目的:在一组筛选了26个相关基因的SAIDs患者中,评估TNFRSF11A变异的患病率,并描述疾病表型表达。
结果:167名患者中总共有12名,7男,发病时年龄(中位数)38岁,产生至少一个TNFRSF11A罕见变异。所有患者在至少一个其他SAID相关基因中携带共存变体,最常见的MEFV(6例),还有TNFRSF1A,NOD2,NLRP3,NLRP7,MVK,IL36RN,RBCK1、PLCG2和PSMB8。SAID发作持续(中位数)9天,表现为高烧(91%),肌痛(75%),萎靡不振(67%),浆膜炎(58%),关节痛/关节炎(58%),胃肠道受累(33%),皮疹(25%),对皮质类固醇有反应.最常见的初始临床诊断是TNF相关的周期性发热综合征(TRAPS),那是,然而,确认,只有一个病人。MEFV变异的出现支持了2例非典型家族性地中海热的诊断,而Yao综合征的诊断是在两名NOD2变异患者中推测的。其余7例患者存在非典型疾病和无法明确诊断,支持TNFRSF11A变体可能参与SAIDs的表型表达。
结论:TNFRSF11A变体,发生在7%的SAID患者总是与其他SAID相关的基因变异,有助于类似于TRAPS的自身炎症综合征的发展。显然有必要进行其他研究以确认新的致病性SAID途径。