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Chronic Lymphocytic Leukemia Patients Have a Preserved Cytomegalovirus-Specic Antibody Response despite Progressive Hypogammaglobulinemia.doc

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

Chronic Lymphocytic Leukemia Patients Have a Preserved Cytomegalovirus-Specific Antibody Response despite Progressive Hypogammaglobulinemia Katrina Vanura Robert Strassl 1 , Franz Rieder , Elisabeth Puchhammer-St?ckl , Wolfgang Graninger , Ulrich J?ger 2 , Marie-Theres Kastner , Thomas Perkmann , Christoph Steininger 2* 2 , Julia Biebl 2 , Michael Sandhofer 2 , Trang Le 1 , 3 3 4 , Christoph F. Steininger 2 , Kostas Stamatopoulos 5 2 1 1 Department of Medicine I, Div. of Hematology and Hemostaseology, Comprehensive Cancer Center (CCC), Medical University of Vienna, Vienna, Austria, 2 Department of Medicine I, Div. of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria, 3 Department of Virology, Medical University of Vienna, Vienna, Austria, 4 Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria, 5 Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece 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; p0.001). 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=