NIHR, Leeds, UK.
University College London, London, UK.
Arthritis Rheumatol. 2019 Dec;71(12):2121-2125. doi: 10.1002/art.41030. Epub 2019 Oct 14.
To assess the prevalence of the MYD88 L265P mutation and variants within NLRP3 and evaluate the status of oligoclonal hematopoiesis in 30 patients with Schnitzler syndrome (SchS).
Thirty patients with SchS were recruited from 3 clinical centers. Six patients with known acquired cryopyrin-associated periodic syndromes (aCAPS) were included as controls. Allele-specific oligonucleotide-polymerase chain reaction was used for the detection of the MYD88 L265P variant, next-generation sequencing was applied to analyze NLRP3 and 28 genes associated with myelodysplastic syndrome, and gene scanning was performed for the detection of X chromosome inactivation.
Activating NLRP3 mutations were not present in 11 SchS patients who had not been sequenced for this gene previously. The MYD88 L265P variant was present in 9 of 30 SchS patients, and somatic mutations associated with clonal hematopoiesis were identified in 1 of 30 patients with SchS and 1 of 6 patients with aCAPS. Evidence of nonrandom X chromosome inactivation was detected in 1 female patient with SchS and 1 female patient with aCAPS.
A shared molecular mechanism accounting for the pathogenesis of inflammation in SchS remains elusive. Clonal hematopoiesis is not associated with other somatic mutations found in individuals with SchS or aCAPS.
评估 30 例 Schnitzler 综合征（SchS）患者中 MYD88 L265P 突变和 NLRP3 内变异的发生率，并评估寡克隆造血的状况。
从 3 个临床中心招募了 30 例 SchS 患者。纳入 6 例已知的获得性 Cryopyrin 相关周期性综合征（aCAPS）作为对照。采用等位基因特异性寡核苷酸-聚合酶链反应检测 MYD88 L265P 变异，应用下一代测序分析 NLRP3 和 28 个与骨髓增生异常综合征相关的基因，并进行基因扫描以检测 X 染色体失活。
先前未对该基因进行测序的 11 例 SchS 患者未发现激活的 NLRP3 突变。30 例 SchS 患者中有 9 例存在 MYD88 L265P 变异，在 1 例 SchS 患者和 1 例 aCAPS 患者中发现与克隆性造血相关的体细胞突变。在 1 例 SchS 女性患者和 1 例 aCAPS 女性患者中检测到非随机 X 染色体失活的证据。
SchS 炎症发病机制的共同分子机制仍难以捉摸。克隆性造血与 SchS 或 aCAPS 个体中发现的其他体细胞突变无关。
