Khwaja Jahanzaib, Vos Josephine M I, Pluimers Tessa E, Japzon Nicole, Patel Aisha, Salter Simon, Kwakernaak Arjan J, Gupta Rajeev, Rismani Ali, Kyriakou Charalampia, Wechalekar Ashutosh D, D'Sa Shirley
Department of Haematology, University College London Hospital, London, UK.
Department of Haematology, Amsterdam UMC, Amsterdam, The Netherlands.
Br J Haematol. 2024 Jan;204(1):177-185. doi: 10.1111/bjh.19112. Epub 2023 Sep 19.
Monoclonal immunoglobulin M-associated type I cryoglobulinaemia is poorly characterised. We screened 534 patients with monoclonal IgM disorders over a 9-year period and identified 134 patients with IgM type I cryoglobulins. Of these, 76% had Waldenström macroglobulinaemia (WM), 5% had other non-Hodgkin lymphoma (NHL) and 19% had IgM monoclonal gammopathy of undetermined significance (MGUS). Clinically relevant IgM-associated disorders (including cold agglutinin disease [CAD], anti-MAG antibodies, amyloidosis and Schnitzler syndrome) coexisted in 31%, more frequently in MGUS versus WM/NHL (72% vs. 22%/29%, p < 0.001). The majority of those with cryoglobulins and coexistent CAD/syndrome had the molecular characteristics of a CAD clone (wild-type MYD88 in 80%). A half of all patients had active manifestations at cryoglobulin detection: vasomotor (22%), cutaneous (16%), peripheral neuropathy (22%) and hyperviscosity (9%). 16/134 required treatment for cryoglobulin-related symptoms alone at a median of 38 days (range: 6-239) from cryoglobulin detection. At a median follow-up of 3 years (range: 0-10), 3-year cryoglobulinaemia-treatment-free survival was 77% (95% CI: 68%-84%). Age was the only predictor of overall survival. Predictors of cryoglobulinaemia-related treatment/death were hyperviscosity (HR: 73.01; 95% CI: 15.62-341.36, p < 0.0001) and cutaneous involvement (HR: 2.95; 95% CI: 1.13-7.71, p = 0.028). Type I IgM cryoglobulinaemia is more prevalent than previously described in IgM gammopathy and should be actively sought.
单克隆免疫球蛋白M相关的I型冷球蛋白血症的特征尚不明确。我们在9年时间里对534例单克隆IgM疾病患者进行了筛查，确定了134例I型IgM冷球蛋白血症患者。其中，76%患有华氏巨球蛋白血症（WM），5%患有其他非霍奇金淋巴瘤（NHL），19%患有意义未明的IgM单克隆丙种球蛋白病（MGUS）。临床相关的IgM相关疾病（包括冷凝集素病[CAD]、抗MAG抗体、淀粉样变性和施尼茨勒综合征）在31%的患者中共存，在MGUS中比在WM/NHL中更常见（72%对22%/29%，p<0.001）。大多数伴有冷球蛋白血症和共存CAD/综合征的患者具有CAD克隆的分子特征（80%为野生型MYD88）。所有患者中有一半在检测到冷球蛋白时出现了活动表现：血管舒缩症状（22%）、皮肤症状（16%）、周围神经病变（22%）和高黏滞血症（9%）。16/134例患者仅因冷球蛋白相关症状而需要治疗，从检测到冷球蛋白起的中位时间为38天（范围：6 - 239天）。在中位随访3年（范围：0 - 10年）时，3年无冷球蛋白血症治疗生存率为77%（95%CI：68% - 84%）。年龄是总生存的唯一预测因素。冷球蛋白血症相关治疗/死亡的预测因素是高黏滞血症（HR：73.01；95%CI：15.62 - 341.36，p<0.0001）和皮肤受累（HR：2.95；95%CI：1.13 - 7.71，p = 0.028）。I型IgM冷球蛋白血症在IgM丙种球蛋白病中比之前描述的更为普遍，应积极筛查。
