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

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

Abstract

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.

Keywords: antimicrobial antibodies; autoantibodies; chronic lymphocytic leukemia; protein microarrays.

Grants and funding

We gratefully acknowledge Fondos FEDER (EU) and Junta Castilla-León (COVID-19 grant COV20EDU/00187). The Proteomics Unit belongs to ProteoRed (PRB3-ISCIII), which was supported by grant no. PT17/0019/0023 of the PE I + D + I 2017-2020 funded by ISCIII and FEDER. A.L.-V. was supported by the VIII Centenario USAL PhD Program, and P.J.-V. was supported by the JCYL PhD Program “JCYL Nos Impulsa” and scholarship JCYL-EDU/601/2020. This research work was performed in the framework of the Nanomedicine CSIC HUB (ref. 202180E048). A.L.-V., C.A.-H., P.J.-V., M.L.G.-V., Á.-P.H. and M.F. are part of the CSIC’s Global Health Platform (PTI SaludGlobal). C.A.-H. was supported by the Instituto de Investigación Biomédica de Salamanca, IBSAL (Programa Puente Contratos Predoctorales-2021) and Junta Castilla-Leon PhD Program “Nos Impulsa” (JCYL-EDU/842/2022).