慢性淋巴细胞白血病中抗原刺激的系统评价：体液免疫作为疾病进展的生物标志物

Systematic Evaluation of Antigenic Stimulation in Chronic Lymphocytic Leukemia: Humoral Immunity as Biomarkers for Disease Evolution.

作者信息

Landeira-Viñuela Alicia, Alcoceba-Sanchez Miguel, Navarro-Bailón Almudena, Arias-Hidalgo Carlota, Juanes-Velasco Pablo, Sánchez-Santos José Manuel, Lecrevisse Quentin, Pedreira Carlos Eduardo, García-Vaquero Marina L, Hernández Ángela-Patricia, Montalvillo Enrique, Góngora Rafael, De Las Rivas Javier, González-Díaz Marcos, Orfao Alberto, Fuentes Manuel

机构信息

Department of Medicine and General Service of Cytometry, CIBERONC-CB16/12/00400, Cancer Research Centre-IBMCC, CSIC-USAL, IBSAL, Campus Miguel de Unamuno s/n, University of Salamanca-CSIC, 37008 Salamanca, Spain.

Department of Hematology, Center Research-Centre IBMCC (CSIC-USAL, IBSAL), University Hospital of Salamanca, CIBERONC-CB16/12/00233, 37007 Salamanca, Spain.

出版信息

Cancers (Basel). 2023 Jan 31;15(3):891. doi: 10.3390/cancers15030891.

DOI:10.3390/cancers15030891

PMID:36765855

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9913429/

Abstract

UNLABELLED

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Studies of CLL antibody reactivity have shown differential targets to autoantigens and antimicrobial molecular motifs that support the current hypothesis of CLL pathogenesis.

METHODS

In this study, we conducted a quantitative serum analysis of 7 immunoglobulins in CLL and monoclonal B-cell lymphocytosis (MBL) patients (bead-suspension protein arrays) and a serological profile (IgG and IgM) study of autoantibodies and antimicrobial antigens (protein microarrays).

RESULTS

Significant differences in the IgA levels were observed according to disease progression and evolution as well as significant alterations in IgG1 according to IGHV mutational status. More representative IgG autoantibodies in the cohort were against nonmutagenic proteins and IgM autoantibodies were against vesicle proteins. Antimicrobial IgG and IgM were detected against microbes associated with respiratory tract infections.

CONCLUSIONS

Quantitative differences in immunoglobulin serum levels could be potential biomarkers for disease progression. In the top 5 tumoral antigens, we detected autoantibodies (IgM and IgG) against proteins related to cell homeostasis and metabolism in the studied cohort. The top 5 microbial antigens were associated with respiratory and gastrointestinal infections; moreover, the subsets with better prognostics were characterized by a reactivation of Cytomegalovirus. The viral humoral response could be a potential prognosis biomarker for disease progression.

摘要

未标记

慢性淋巴细胞白血病（CLL）是西方世界最常见的白血病。对CLL抗体反应性的研究表明，其自身抗原和抗菌分子基序的靶点存在差异，这支持了当前关于CLL发病机制的假说。

方法

在本研究中，我们对CLL和单克隆B细胞淋巴细胞增多症（MBL）患者的7种免疫球蛋白进行了定量血清分析（珠悬液蛋白阵列），并对自身抗体和抗菌抗原进行了血清学分析（IgG和IgM）（蛋白质微阵列）。

结果

根据疾病进展和演变观察到IgA水平存在显著差异，根据IGHV突变状态观察到IgG1存在显著改变。该队列中更具代表性的IgG自身抗体针对非诱变蛋白，IgM自身抗体针对囊泡蛋白。检测到针对与呼吸道感染相关微生物的抗菌IgG和IgM。

结论

免疫球蛋白血清水平的定量差异可能是疾病进展的潜在生物标志物。在排名前5的肿瘤抗原中，我们在研究队列中检测到针对与细胞稳态和代谢相关蛋白质的自身抗体（IgM和IgG）。排名前5的微生物抗原与呼吸道和胃肠道感染相关；此外，预后较好的亚组的特征是巨细胞病毒重新激活。病毒体液反应可能是疾病进展的潜在预后生物标志物。