title: Chronic lymphocytic leukemia patients have a preserved cytomegalovirus-specific antibody response despite progressive hypogammaglobulinemia.
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.
authors.affiliation: Department of Medicine I, Div. of Hematology and Hemostaseology, Comprehensive Cancer Center (CCC), Medical University of Vienna, Vienna, Austria.
authors.forename: Katrina
authors.initials: K
authors.lastname: Vanura
authors.forename: Franz
authors.initials: F
authors.lastname: Rieder
authors.forename: Marie-Theres
authors.initials: MT
authors.lastname: Kastner
authors.forename: Julia
authors.initials: J
authors.lastname: Biebl
authors.forename: Michael
authors.initials: M
authors.lastname: Sandhofer
authors.forename: Trang
authors.initials: T
authors.lastname: Le
authors.forename: Robert
authors.initials: R
authors.lastname: Strassl
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Puchhammer-Stöckl
authors.forename: Thomas
authors.initials: T
authors.lastname: Perkmann
authors.forename: Christoph F
authors.initials: CF
authors.lastname: Steininger
authors.forename: Kostas
authors.initials: K
authors.lastname: Stamatopoulos
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Graninger
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jäger
authors.forename: Christoph
authors.initials: C
authors.lastname: Steininger
mesh_terms: D000361:Agammaglobulinemia / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology*; D001483:Base Sequence; D003587:Cytomegalovirus / Q000276:immunology*; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007700:Kinetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D016013:Likelihood Functions; D008957:Models, Genetic; D008969:Molecular Sequence Data; D021141:Nucleic Acid Amplification Techniques; D010750:Phosphoproteins / Q000235:genetics; D010802:Phylogeny; D011446:Prospective Studies; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D014763:Viral Matrix Proteins / Q000235:genetics; D014766:Viremia / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D017931:DNA Primers; D004279:DNA, Viral; D007074:Immunoglobulin G; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C056367:pp150 protein, Cytomegalovirus