Improved vaccination response during ranitidine treatment, and increased plasma histamine concentrations, in patients with B cell chronic lymphocytic leukemia.
Patients with B cell chronic lymphocytic leukemia (B-CLL) have decreased capacity to mount relevant antibody responses upon immunization, and development of hypogammaglobulinemia is part of the natural history of the disease. We investigated the influence of histamine type-2 (H2) receptor blockade by ranitidine on the in vivo antibody production in B-CLL patients following vaccination. Anti-polysaccharide antibodies in B-CLL patients, vaccinated with a tetanus-toxoid conjugated vaccine against Haemophilus influenzae type-B (Hib), reached long-term protective levels in more than 90% of B-CLL patients randomized to ranitidine treatment, as compared to 43% of the untreated patients (P = 0.024). No difference in the response to vaccination against influenza virus types A and B protein could be detected between the two groups. Plasma histamine levels were 2-fold to 20-fold higher in 23 out of 31 B-CLL patients, compared to normal controls, and these levels showed a significant positive correlation to disease duration. These findings indicate the possibility of improving in vivo antibody production against a highly relevant pathogen in B-CLL patients by histamine type-2 receptor blockade, and the combined finding of an immune-stimulatory effect of ranitidine and increased plasma histamine levels, strongly suggests the involvement of histamine in the pathogenesis of B-CLL immunodeficiency.
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D002478:Cells, Cultured; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D018073:Haemophilus Vaccines / Q000276:immunology*; D006632:Histamine / Q000097:blood*; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D006801:Humans; D007377:Interleukin-3 / Q000097:blood; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011899:Ranitidine / Q000627:therapeutic use*; D017455:Receptors, IgE / Q000378:metabolism; D014611:Vaccination
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D018073:Haemophilus Vaccines; D006635:Histamine H2 Antagonists; D007377:Interleukin-3; D017455:Receptors, IgE; D006632:Histamine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011899:Ranitidine