Department of Pediatrics and Pediatric Rheumatology, Hadassah Hebrew University Medical Center, Mount Scopus, Jerusalem, Israel.
Semin Arthritis Rheum. 2012 Aug;42(1):84-8. doi: 10.1016/j.semarthrit.2011.12.002. Epub 2012 Jan 12.
Familial Mediterranean fever (FMF) and Crohn's disease are autoinflammatory disorders, associated with genes (MEFV and NOD2/CARD15, respectively) encoding for regulatory proteins, important in innate immunity, apoptosis, cytokine processing, and inflammation. Although mutations in the MEFV gene were shown to modify Crohn's disease, the role of NOD2/CARD15 gene mutations in the FMF disease phenotype was never studied before.
The cohort consisted of 103 consecutive children with FMF, followed in a single referral center. NOD2/CARD15 genotypes were analyzed in all patients and 299 ethnically matched unaffected controls. Demographic data, clinical characteristics, and disease course of FMF patients with and without NOD2/CARD15 mutation were compared.
A single NOD2/CARD15 mutation was detected in 10 (9.7%) FMF patients and 26 (8.7%) controls. No homozygous or compound heterozygous subjects were discovered in the 2 groups. FMF patients carrying a NOD2/CARD15 mutation had a higher rate of erysipelas-like erythema and acute scrotum attacks, a trend for a higher rate of colchicine resistance and a more severe disease as compared with patients without mutations.
NOD2/CARD15 mutations are not associated with an increased susceptibility to develop FMF. Nevertheless, the presence of these mutations in FMF patients appears to be associated with a trend to a more severe disease.
家族性地中海热（FMF）和克罗恩病是自身炎症性疾病，分别与编码调节蛋白的基因（MEFV 和 NOD2/CARD15）相关，这些调节蛋白在先天免疫、细胞凋亡、细胞因子处理和炎症中起重要作用。虽然已经证明 MEFV 基因突变可改变克罗恩病的发病风险，但 NOD2/CARD15 基因突变在 FMF 疾病表型中的作用尚未得到研究。
该队列包括 103 例连续的 FMF 患儿，在单一转诊中心进行随访。对所有患者和 299 名具有相同种族背景的无病对照者进行 NOD2/CARD15 基因型分析。比较 NOD2/CARD15 基因突变阳性和阴性 FMF 患者的人口统计学资料、临床特征和疾病过程。
在 10 例（9.7%）FMF 患者和 26 例（8.7%）对照者中检测到单个 NOD2/CARD15 突变。两组均未发现纯合子或复合杂合子。与无突变的 FMF 患者相比，携带 NOD2/CARD15 突变的 FMF 患者发生丹毒样红斑和急性阴囊炎的频率更高，对秋水仙碱的耐药率呈升高趋势，疾病更严重。
NOD2/CARD15 突变与发生 FMF 的易感性增加无关。然而，这些突变在 FMF 患者中的存在似乎与更严重疾病的趋势相关。
