Abstract：
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.
摘要：
单克隆免疫球蛋白M相关的I型冷球蛋白血症缺乏表征。我们在9年内筛选了534例单克隆IgM疾病患者，并确定了134例I型IgM冷球蛋白患者。其中,76%患有Waldenström巨球蛋白血症（WM），5％患有其他非霍奇金淋巴瘤（NHL），19％患有未知意义的IgM单克隆丙种球蛋白病（MGUS）。临床相关的IgM相关疾病（包括冷凝集素疾病[CAD]，抗MAG抗体，淀粉样变性和Schnitzler综合征）共存31%，MGUS与WM/NHL的比较频繁(72%与22%/29%，p<0.001)。大多数患有冷球蛋白和共存的CAD/综合征的人具有CAD克隆的分子特征（80％的野生型MYD88）。所有患者中有一半在冷球蛋白检测时表现活跃：血管舒缩（22％），皮肤（16％），周围神经病变（22％）和高粘度（9％）。16/134需要单独治疗冷球蛋白相关症状，中位数为38天（范围：6-239）从冷球蛋白检测。中位随访3年（范围：0-10），3年无冷球蛋白血症治疗生存率为77%(95%CI:68%-84%)。年龄是总生存率的唯一预测因子。冷球蛋白血症相关治疗/死亡的预测因素是高粘滞度(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冷球蛋白血症比先前在IgM丙种球蛋白病中描述的更为普遍，应积极寻求。
