Chronic lymphocytic leukemia patients have a preserved cytomegalovirus-specific antibody response despite progressive hypogammaglobulinemia

PLoS One. 2013 Oct 23;8(10):e78925. doi: 10.1371/journal.pone.0078925. eCollection 2013.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agammaglobulinemia / immunology*
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology*
  • Antibody Formation / immunology*
  • Base Sequence
  • Cytomegalovirus / immunology*
  • DNA Primers / genetics
  • DNA, Viral / genetics
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunoglobulin G / immunology
  • Kinetics
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Likelihood Functions
  • Models, Genetic
  • Molecular Sequence Data
  • Nucleic Acid Amplification Techniques
  • Phosphoproteins / genetics
  • Phylogeny
  • Prospective Studies
  • Sequence Analysis, DNA
  • Species Specificity
  • Viral Matrix Proteins / genetics
  • Viremia / immunology

Substances

  • Antibodies, Viral
  • DNA Primers
  • DNA, Viral
  • Immunoglobulin G
  • Phosphoproteins
  • Viral Matrix Proteins
  • pp150 protein, Cytomegalovirus