Mediterranean fever gene variants modify clinical phenotypes of idiopathic multi-centric Castleman disease,Clinical & Experimental Immunology

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Mediterranean fever gene variants modify clinical phenotypes of idiopathic multi-centric Castleman disease
Clinical & Experimental Immunology ( IF 3.4 ) Pub Date : 2021-06-07 , DOI: 10.1111/cei.13632
Yushiro Endo ₁ , Tomohiro Koga ₁ , Yoshihumi Ubara ₂ , Remi Sumiyoshi ₁ , Kaori Furukawa ₁ , Atsushi Kawakami ₁

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Four cases of idiopathic multi-centric Castleman disease (iMCD) reportedly have variants in hereditary autoinflammatory disease-related genes; however, the frequency and role of these variants in iMCD is still unknown. We therefore investigated such gene variants among patients with iMCD and aimed to reveal the relationship between iMCD and autoinflammatory disease-related genes. We reviewed 14 Japanese iMCD patients who were recruited between January 2015 and September 2019. All patients met both the Japanese tentative diagnostic criteria for Castleman disease and the international consensus diagnostic criteria for iMCD. We performed genetic analyses for 31 autoinflammatory disease-related genes by targeted next-generation sequencing. The MEFV gene variants were observed in 10 of 14 patients with iMCD. Although iMCD had a high percentage of exons 2 or 3 variants of MEFV, comparison of data from healthy Japanese subjects indicated that there was no significant difference in the percentage between healthy Japanese subjects and patients with iMCD. Variants of uncertain significance (VUS) in the TNFRSF1A and CECR1 genes were observed in two of the patients, respectively. We divided patients into two groups—those with MEFV variants (excluding E148Q variants) and those without MEFV variants—and compared the clinical characteristics between these two groups. Patients with MEFV variants, excluding E148Q variants, exhibited a significantly higher likelihood of fever and significantly lower levels of hemoglobin than those lacking MEFV variants. Our results indicated that patients with iMCD tended to have a high frequency of MEFV gene variants and the presence of such variants can affect iMCD clinical phenotypes.

中文翻译：

地中海热基因变异改变特发性多中心卡斯尔曼病的临床表型

据报道，4 例特发性多中心 Castleman 病 (iMCD) 具有遗传性自身炎症性疾病相关基因的变异；然而，这些变体在 iMCD 中的频率和作用仍然未知。因此，我们研究了 iMCD 患者中的此类基因变异，旨在揭示 iMCD 与自身炎症性疾病相关基因之间的关系。我们回顾了 2015 年 1 月至 2019 年 9 月期间招募的 14 名日本 iMCD 患者。所有患者均符合日本 Castleman 病暂定诊断标准和 iMCD 国际共识诊断标准。我们通过靶向二代测序对 31 个自身炎症性疾病相关基因进行了遗传分析。该MEFV在 14 名 iMCD 患者中有 10 名观察到基因变异。尽管 iMCD 的MEFV外显子 2 或 3 变体的百分比很高，但比较来自日本健康受试者的数据表明，日本健康受试者和 iMCD 患者之间的百分比没有显着差异。分别在两名患者中观察到TNFRSF1A和CECR1基因中存在不确定意义的变异 (VUS) 。我们将患者分为两组——有MEFV变异（不包括 E148Q 变异）的和没有MEFV变异的——并比较了这两组之间的临床特征。MEFV患者除 E148Q 变体外，与缺乏MEFV变体的变体相比，变体表现出更高的发烧可能性和显着降低的血红蛋白水平。我们的结果表明，iMCD 患者往往具有高频率的MEFV基因变异，并且此类变异的存在会影响 iMCD 临床表型。

更新日期：2021-06-07

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