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

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 q...

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Main Authors: Alicia Landeira-Viñuela, Miguel Alcoceba-Sanchez, Almudena Navarro-Bailón, Carlota Arias-Hidalgo, Pablo Juanes-Velasco, José Manuel Sánchez-Santos, Quentin Lecrevisse, Carlos Eduardo Pedreira, Marina L. García-Vaquero, Ángela-Patricia Hernández, Enrique Montalvillo, Rafael Góngora, Javier De las Rivas, Marcos González-Díaz, Alberto Orfao, Manuel Fuentes
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/15/3/891
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author Alicia Landeira-Viñuela
Miguel Alcoceba-Sanchez
Almudena Navarro-Bailón
Carlota Arias-Hidalgo
Pablo Juanes-Velasco
José Manuel Sánchez-Santos
Quentin Lecrevisse
Carlos Eduardo Pedreira
Marina L. García-Vaquero
Ángela-Patricia Hernández
Enrique Montalvillo
Rafael Góngora
Javier De las Rivas
Marcos González-Díaz
Alberto Orfao
Manuel Fuentes
author_facet Alicia Landeira-Viñuela
Miguel Alcoceba-Sanchez
Almudena Navarro-Bailón
Carlota Arias-Hidalgo
Pablo Juanes-Velasco
José Manuel Sánchez-Santos
Quentin Lecrevisse
Carlos Eduardo Pedreira
Marina L. García-Vaquero
Ángela-Patricia Hernández
Enrique Montalvillo
Rafael Góngora
Javier De las Rivas
Marcos González-Díaz
Alberto Orfao
Manuel Fuentes
author_sort Alicia Landeira-Viñuela
collection DOAJ
description 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.
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spelling doaj.art-fad604c9757e46738dbe811d746d8c1e2023-11-16T16:18:48ZengMDPI AGCancers2072-66942023-01-0115389110.3390/cancers15030891Systematic Evaluation of Antigenic Stimulation in Chronic Lymphocytic Leukemia: Humoral Immunity as Biomarkers for Disease EvolutionAlicia Landeira-Viñuela0Miguel Alcoceba-Sanchez1Almudena Navarro-Bailón2Carlota Arias-Hidalgo3Pablo Juanes-Velasco4José Manuel Sánchez-Santos5Quentin Lecrevisse6Carlos Eduardo Pedreira7Marina L. García-Vaquero8Ángela-Patricia Hernández9Enrique Montalvillo10Rafael Góngora11Javier De las Rivas12Marcos González-Díaz13Alberto Orfao14Manuel Fuentes15Department 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, SpainDepartment of Hematology, Center Research-Centre IBMCC (CSIC-USAL, IBSAL), University Hospital of Salamanca, CIBERONC-CB16/12/00233, 37007 Salamanca, SpainDepartment of Hematology, Center Research-Centre IBMCC (CSIC-USAL, IBSAL), University Hospital of Salamanca, CIBERONC-CB16/12/00233, 37007 Salamanca, SpainDepartment 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, SpainDepartment 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, SpainStatistics Department, University of Salamanca, 37008 Salamanca, SpainDepartment 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, SpainSystems and Computing Department (COPPE-PESC), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-914, BrazilDepartment 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, SpainDepartment 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, SpainDepartment 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, SpainDepartment 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, SpainBioinformatics and Functional Genomics Group, Cancer Research Center (CiC-IBMCC, CSIC/USAL), Consejo Superior de Investigaciones Científicas (CSIC) and University of Salamanca (USAL), 37008 Salamanca, SpainDepartment of Hematology, Center Research-Centre IBMCC (CSIC-USAL, IBSAL), University Hospital of Salamanca, CIBERONC-CB16/12/00233, 37007 Salamanca, SpainDepartment 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, SpainDepartment 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, SpainChronic 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.https://www.mdpi.com/2072-6694/15/3/891chronic lymphocytic leukemiaantimicrobial antibodiesautoantibodiesprotein microarrays
spellingShingle Alicia Landeira-Viñuela
Miguel Alcoceba-Sanchez
Almudena Navarro-Bailón
Carlota Arias-Hidalgo
Pablo Juanes-Velasco
José Manuel Sánchez-Santos
Quentin Lecrevisse
Carlos Eduardo Pedreira
Marina L. García-Vaquero
Ángela-Patricia Hernández
Enrique Montalvillo
Rafael Góngora
Javier De las Rivas
Marcos González-Díaz
Alberto Orfao
Manuel Fuentes
Systematic Evaluation of Antigenic Stimulation in Chronic Lymphocytic Leukemia: Humoral Immunity as Biomarkers for Disease Evolution
Cancers
chronic lymphocytic leukemia
antimicrobial antibodies
autoantibodies
protein microarrays
title Systematic Evaluation of Antigenic Stimulation in Chronic Lymphocytic Leukemia: Humoral Immunity as Biomarkers for Disease Evolution
title_full Systematic Evaluation of Antigenic Stimulation in Chronic Lymphocytic Leukemia: Humoral Immunity as Biomarkers for Disease Evolution
title_fullStr Systematic Evaluation of Antigenic Stimulation in Chronic Lymphocytic Leukemia: Humoral Immunity as Biomarkers for Disease Evolution
title_full_unstemmed Systematic Evaluation of Antigenic Stimulation in Chronic Lymphocytic Leukemia: Humoral Immunity as Biomarkers for Disease Evolution
title_short Systematic Evaluation of Antigenic Stimulation in Chronic Lymphocytic Leukemia: Humoral Immunity as Biomarkers for Disease Evolution
title_sort systematic evaluation of antigenic stimulation in chronic lymphocytic leukemia humoral immunity as biomarkers for disease evolution
topic chronic lymphocytic leukemia
antimicrobial antibodies
autoantibodies
protein microarrays
url https://www.mdpi.com/2072-6694/15/3/891
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