意义未明的单克隆丙种球蛋白病和多发性骨髓瘤中的单核细胞亚群以及血清炎症和骨相关标志物
Monocyte Subsets and Serum Inflammatory and Bone-Associated Markers in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma.
作者信息
Damasceno Daniela, Almeida Julia, Teodosio Cristina, Sanoja-Flores Luzalba, Mayado Andrea, Pérez-Pons Alba, Puig Noemi, Arana Paula, Paiva Bruno, Solano Fernando, Romero Alfonso, Matarraz Sergio, van den Bossche Wouter B L, Flores-Montero Juan, Durie Brian, van Dongen Jacques J M, Orfao Alberto
机构信息
Translational and Clinical Research Program, Cancer Research Center (IBMCC, USAL-CSIC), Cytometry Service (NUCLEUS) and Department of Medicine, University of Salamanca and Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain.
Biomedical Research Networking Centre Consortium of Oncology (CIBERONC) (CB16/12/00400), Instituto Carlos III, 28029 Madrid, Spain.
出版信息
Cancers (Basel). 2021 Mar 22;13(6):1454. doi: 10.3390/cancers13061454.
BACKGROUND
Monocyte/macrophages have been shown to be altered in monoclonal gammopathy of undetermined significance (MGUS), smoldering (SMM) and active multiple myeloma (MM), with an impact on the disruption of the homeostasis of the normal bone marrow (BM) microenvironment.
METHODS
We investigated the distribution of different subsets of monocytes (Mo) in blood and BM of newly-diagnosed untreated MGUS ( = 23), SMM ( = 14) and MM ( = 99) patients vs. healthy donors (HD; = 107), in parallel to a large panel of cytokines and bone-associated serum biomarkers.
RESULTS
Our results showed normal production of monocyte precursors and classical Mo (cMo) in MGUS, while decreased in SMM and MM ( ≤ 0.02), in association with lower blood counts of recently-produced CD62L cMo in SMM ( = 0.004) and of all subsets of (CD62L, CD62L and FcεRI) cMo in MM ( ≤ 0.02). In contrast, intermediate and end-stage non-classical Mo were increased in BM of MGUS ( ≤ 0.03), SMM ( ≤ 0.03) and MM ( ≤ 0.002), while normal (MGUS and SMM) or decreased (MM; = 0.01) in blood. In parallel, increased serum levels of interleukin (IL)1β were observed in MGUS ( = 0.007) and SMM ( = 0.01), higher concentrations of serum IL8 were found in SMM ( = 0.01) and MM ( = 0.002), and higher serum IL6 ( = 0.002), RANKL ( = 0.01) and bone alkaline phosphatase (BALP) levels ( = 0.01) with decreased counts of FcεRI cMo, were restricted to MM presenting with osteolytic lesions. This translated into three distinct immune/bone profiles: (1) normal (typical of HD and most MGUS cases); (2) senescent-like (increased IL1β and/or IL8, found in a minority of MGUS, most SMM and few MM cases with no bone lesions); and (3) pro-inflammatory-high serum IL6, RANKL and BALP with significantly ( = 0.01) decreased blood counts of immunomodulatory FcεRI cMo-, typical of MM presenting with bone lesions.
CONCLUSIONS
These results provide new insight into the pathogenesis of plasma cell neoplasms and the potential role of FcεRI cMo in normal bone homeostasis.
背景
已表明在意义未明的单克隆丙种球蛋白病（MGUS）、冒烟型（SMM）和活动性多发性骨髓瘤（MM）中，单核细胞/巨噬细胞发生改变，这对正常骨髓（BM）微环境稳态的破坏有影响。
方法
我们研究了新诊断未治疗的MGUS（n = 23）、SMM（n = 14）和MM（n = 99）患者与健康供者（HD；n = 107）血液和骨髓中不同单核细胞（Mo）亚群的分布，同时检测了大量细胞因子和骨相关血清生物标志物。
结果
我们的结果显示，MGUS中单核细胞前体和经典Mo（cMo）产生正常，而SMM和MM中则减少（P≤0.02），这与SMM中近期产生的CD62L+cMo血液计数较低（P = 0.004）以及MM中所有（CD62L+、CD62L - 和FcεRI+）cMo亚群计数较低（P≤0.02）相关。相反，MGUS（P≤0.03）、SMM（P≤0.03）和MM（P≤0.002）骨髓中中间期和终末期非经典Mo增加，而血液中正常（MGUS和SMM）或减少（MM；P = 0.01）。同时，MGUS（P = 0.007）和SMM（P = 0.01）中观察到血清白细胞介素（IL）1β水平升高，SMM（P = 0.01）和MM（P = 0.002）中发现血清IL8浓度较高，血清IL6（P = 0.002）、RANKL（P = 0.01）和骨碱性磷酸酶（BALP）水平较高且FcεRI+cMo计数减少，仅限于有溶骨性病变的MM。这转化为三种不同的免疫/骨谱：（1）正常（典型的HD和大多数MGUS病例）；（2）衰老样（IL1β和/或IL8升高，见于少数MGUS、大多数SMM和少数无骨病变的MM病例）；（3）促炎 - 高血清IL6、RANKL和BALP，免疫调节性FcεRI+cMo血液计数显著（P = 0.01）降低，典型的有骨病变的MM。
结论
这些结果为浆细胞肿瘤的发病机制以及FcεRI+cMo在正常骨稳态中的潜在作用提供了新的见解。
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