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Polyclonal serum free light chain elevation is associated with increased risk of monoclonal gammopathies.
Blood Cancer Journal ( IF 12.9 ) Pub Date : 2019-05-17 , DOI: 10.1038/s41408-019-0210-z Shaji Kumar 1 , Dirk R Larson 2 , Angela Dispenzieri 1 , Terry M Therneau 2 , David L Murray 3 , P Leif Bergsagel 4 , Robert A Kyle 1 , S Vincent Rajkumar 1
Blood Cancer Journal ( IF 12.9 ) Pub Date : 2019-05-17 , DOI: 10.1038/s41408-019-0210-z Shaji Kumar 1 , Dirk R Larson 2 , Angela Dispenzieri 1 , Terry M Therneau 2 , David L Murray 3 , P Leif Bergsagel 4 , Robert A Kyle 1 , S Vincent Rajkumar 1
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Monoclonal gammopathies (MG) constitute a spectrum of disorders starting from a monoclonal gammopathy of undetermined significance (MGUS) to active disease requiring therapy such as multiple myeloma. MG are characterized by proliferation of clonal plasma cells (PC) secreting a monoclonal protein either as intact immunoglobulin or free kappa or lambda free light chains (FLC). We hypothesized that a polyclonal elevation of serum FLC may indicate an inflammatory state that precedes development of MG. We studied 15,630 individuals from Olmsted county, who did not have MGUS based on baseline screening studies. At a median follow-up of 18.1 years, 264 patients had developed a clonal PC disorder; 252 with MGUS, 1 with SMM, 8 with MM, and 3 with amyloidosis, translating to an annual incidence of development of a MG of 0.1%. We examined the baseline polyclonal ΣFLC (kappa + lambda FLC) from the initial screening and grouped them into deciles. The highest decile group had a 2.6-fold (95% CI; 1.8, 3.7) increase in the risk of developing a MG, P < 0.001. We demonstrate for the first time, the increased risk of developing MG in patients with elevated serum FLC, suggesting that an underlying inflammatory state may play an etiologic role.
中文翻译：
多克隆无血清轻链升高与单克隆同性恋病风险增加有关。
单克隆血友病（MG）构成了一系列疾病，从意义不明的单克隆丙种球蛋白病（MGUS）到需要治疗的活动性疾病，例如多发性骨髓瘤。MG的特征是克隆浆细胞（PC）增殖，分泌完整的免疫球蛋白或游离κ或无λ轻链（FLC）的单克隆蛋白。我们假设血清FLC的多克隆升高可能表明在MG出现之前出现了炎症状态。根据基线筛查研究，我们研究了Olmsted县的15630个人，他们没有MGUS。在中位随访时间为18.1年时，有264例患者发生了克隆性PC疾病。MGUS为252，SMM为1，MM为8，淀粉样变性为3，转化为MG的年发生率为0.1％。我们从最初的筛选中检查了基线多克隆ΣFLC（κ+ lambda FLC）并将其分组为十分位。最高的十分位组患MG的风险增加了2.6倍（95％CI； 1.8、3.7），P <0.001。我们首次证明，血清FLC升高的患者发生MG的风险增加，表明潜在的炎症状态可能起病因作用。
更新日期：2019-11-18
中文翻译：
多克隆无血清轻链升高与单克隆同性恋病风险增加有关。
单克隆血友病（MG）构成了一系列疾病，从意义不明的单克隆丙种球蛋白病（MGUS）到需要治疗的活动性疾病，例如多发性骨髓瘤。MG的特征是克隆浆细胞（PC）增殖，分泌完整的免疫球蛋白或游离κ或无λ轻链（FLC）的单克隆蛋白。我们假设血清FLC的多克隆升高可能表明在MG出现之前出现了炎症状态。根据基线筛查研究，我们研究了Olmsted县的15630个人，他们没有MGUS。在中位随访时间为18.1年时，有264例患者发生了克隆性PC疾病。MGUS为252，SMM为1，MM为8，淀粉样变性为3，转化为MG的年发生率为0.1％。我们从最初的筛选中检查了基线多克隆ΣFLC（κ+ lambda FLC）并将其分组为十分位。最高的十分位组患MG的风险增加了2.6倍（95％CI； 1.8、3.7），P <0.001。我们首次证明，血清FLC升高的患者发生MG的风险增加，表明潜在的炎症状态可能起病因作用。
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