Journal Article

Chronic Lymphocytic Leukemia Patients Have a Preserved Cytomegalovirus-Specific Antibody Response despite Progressive Hypogammaglobulinemia

Stamatopoulos, Kostas, Steininger, Christoph F., Graninger, Wolfgang, Strassl, Robert, Biebl, Julia, Le, Trang, Puchhammer-Stöckl, Elisabeth, Rieder, Franz, Kastner, Marie-Theres, Steininger, Christoph, Sandhofer, Michael, Vanura, Katrina, Perkmann, Thomas, Jäger, Ulrich

2013

Overview

Chronic lymphocytic leukemia (CLL) is characterized by progressive hypogammaglobulinemia predisposing affected patients to a variety of infectious diseases but paradoxically not to cytomegalovirus (CMV) disease. Moreover, we found reactivity of a panel of CLL recombinant antibodies (CLL-rAbs) encoded by a germ-line allele with a single CMV protein, pUL32, despite differing antibody binding motifs. To put these findings into perspective, we studied prospectively relative frequency of viremia, kinetics of total and virus-specific IgG over time, and UL32 genetic variation in a cohort of therapy-naive patients (n=200). CMV-DNA was detected in 3% (6/200) of patients. The decay of total IgG was uniform (mean, 0.03; SD, 0.03) and correlated with that of IgG subclasses 1-4 in the paired samples available (n=64; p<0.001). Total CMV-specific IgG kinetics were more variable (mean, 0,02; SD, 0,06) and mean decay values differed significantly from those of total IgG (p=0.034). Boosts of CMV-specific antibody levels were observed in 49% (22/45) of CMV-seropositive patients. In contrast, VZV- and EBV-specific IgG levels decayed in parallel with total IgG levels (p=0.003 and p=0.001, respectively). VZV-specific IgG even became undetectable in 18% (9/50) of patients whereas CMV-specific ones remained detectable in all seropositive patients. The observed CMV-specific IgG kinetics were predicated upon the highly divergent kinetics of IgG specific for individual antigens - glycoprotein B-specific IgG were boosted in 51% and pUL32-specific IgG in 32% of patients. In conclusion, CLL patients have a preserved CMV-specific antibody response despite progressive decay of total IgG and IgG subclasses. CMV-specific IgG levels are frequently boosted in contrast to that of other herpesviruses indicative of a higher rate of CMV reactivation and antigen-presentation. In contrast to the reactivity of multiple different CLL-rAbs with pUL32, boosts of humoral immunity are triggered apparently by other CMV antigens than pUL32, like glycoprotein B.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Activation / Agammaglobulinemia / Agammaglobulinemia - immunology / Antibodies / Antibodies, Viral - blood / Antibodies, Viral - immunology / Antibody Formation - immunology / Antibody response / Antigen presentation / Antigen-antibody reactions / Antigens / Base Sequence / Cancer / Care and treatment / Chronic lymphocytic leukemia / Cytomegalovirus / Cytomegalovirus - immunology / Cytomegalovirus infections / Decay / Deoxyribonucleic acid / DNA / DNA Primers - genetics / DNA, Viral - genetics / Enzyme-Linked Immunosorbent Assay / Genetic diversity / Glycoprotein B / Glycoproteins / Hematology / Humans / Humoral immunity / Hypogammaglobulinemia / Immunity / Immunoglobulin G / Immunoglobulin G - immunology / Immunoglobulins / Immunology / Immunotherapy / Infectious diseases / Kinetics / Leukemia / Leukemia, Lymphocytic, Chronic, B-Cell - immunology / Likelihood Functions / Lymphatic leukemia / Lymphocytes / Medicine / Models, Genetic / Molecular Sequence Data / Nucleic Acid Amplification Techniques / Patients / Phosphoproteins - genetics / Phylogeny / Prospective Studies / Proteins / Reaction kinetics / Sequence Analysis, DNA / Species Specificity / T cell receptors / Viral Matrix Proteins - genetics / Viremia / Viremia - immunology / Virology / Viruses