Chronic Lymphocytic Leukemia Patients Have a Preserved Cytomegalovirus-Specific Antibody Response despite Progressive HypogammaglobulinemiaReportar como inadecuado

Chronic Lymphocytic Leukemia Patients Have a Preserved Cytomegalovirus-Specific Antibody Response despite Progressive Hypogammaglobulinemia - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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.

Autor: Katrina Vanura, Franz Rieder, Marie-Theres Kastner, Julia Biebl, Michael Sandhofer, Trang Le, Robert Strassl, Elisabeth Puchhamme



Documentos relacionados