单克隆免疫球蛋白M相关的I类冷球蛋白血症缺乏深入的研究。我们在9年的时间内对534例单克隆免疫球蛋白M异常患者进行了筛查，并确定了134例I类冷球蛋白血症患者。其中，76%的患者为Waldenström巨球蛋白血症（WM），5%的患者为其他非何杰金淋巴瘤（NHL），19%的患者为I类免疫球蛋白M单克隆异常增生（MGUS）。31%的患者同时存在临床相关的I类免疫球蛋白M相关疾病（包括寒凝集素病 [CAD]、抗MAG抗体、淀粉样变和Schnitzler综合征），其中MGUS患者相比WM/NHL患者更为频繁（72% vs. 22%/29%，p < 0.001）。大多数同时患有冷球蛋白和CAD/综合征的患者分子特征为CAD克隆（80%为野生型MYD88）。在冷球蛋白检测时，半数患者表现为活动症状：血管舒缩功能障碍（22%）、皮肤损害（16%）、周围神经病变（22%）和高粘滞性血症（9%）。在134例患者中，16例仅因冷球蛋白相关症状而需要治疗，从冷球蛋白检测开始的中位治疗时间为38天（范围：6-239天）。在中位随访时间为3年（范围：0-10年）时，3年冷球蛋白血症无需治疗生存率为77%（95% CI：68%-84%）。年龄是总生存率的唯一预测因素。预测冷球蛋白血症相关治疗/死亡的因素包括高粘滞性血症（HR：73.01；95% CI：15.62-341.36，p < 0.0001）和皮肤损害（HR：2.95；95% CI：1.13-7.71，p = 0.028）。I类免疫球蛋白M冷球蛋白血症在I类免疫球蛋白M异常增生中的患病率高于以往描述的情况，应积极寻找。© 2023年英国血液学会和John Wiley & Sons Ltd.

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.© 2023 British Society for Haematology and John Wiley & Sons Ltd.