title: In vitro production of anti-RBC antibodies and cytokines in chronic lymphocytic leukemia.
abstract: B-chronic lymphocytic leukemia (B-CLL) patients have a high prevalence of autoimmune phenomena, mainly autoimmune hemolytic anemia (AIHA). Immunoregulatory cytokines play a role in the regulation of both autoimmunity and leukemic B-cell growth. Mitogen-stimulated direct antiglobulin test (MS-DAT) is a recently described test able to disclose latent anti-RBC autoimmunity in AIHA. We investigated the prevalence of anti-RBC autoimmunity by MS-DAT and the pattern of cytokine production by PHA-stimulated whole blood cultures from 69 B-CLL patients and 53 controls. Results showed that anti-RBC IgG values in unstimulated, PHA-, PMA-, and PWM-stimulated cultures were significantly higher in B-CLL patients compared with controls. In B-CLL, the prevalence of anti-RBC autoimmunity was 28.9% by MS-DAT, compared with 4.3% by the standard DAT. Production of IFN-gamma, IL-2, IL-13, TNF-alpha, sCD23, and sCD30 was significantly increased in all B-CLL patients compared with controls, whereas there was no difference in IL-4, IL-6, IL-10, and TGF-beta production. Multivariate analysis showed that IL-4 was significantly increased in MS-DAT-positive compared with -negative patients. Patients with autoantibody positivity displayed greater IFN-gamma production than negative patients. These data are in line with the hypothesis that autoimmune phenomena in B-CLL are associated with an imbalance towards a Th-2-like profile. The elevated prevalence of anti-RBC autoimmunity found by MS-DAT suggests that an underestimated latent autoimmunity exists in B-CLL.
authors.affiliation: Dipartimento di Ematologia, IRCCS Ospedale Maggiore di Milano, Via F. Sforza 35, 20122 Milan, Italy. wbarcel@polic.cilea.it
authors.forename: W
authors.initials: W
authors.lastname: Barcellini
authors.forename: R
authors.initials: R
authors.lastname: Montesano
authors.forename: G
authors.initials: G
authors.lastname: Clerici
authors.forename: A
authors.initials: A
authors.lastname: Zaninoni
authors.forename: F G
authors.initials: FG
authors.lastname: Imperiali
authors.forename: R
authors.initials: R
authors.lastname: Calori
authors.forename: A
authors.initials: A
authors.lastname: Cortelezzi
authors.forename: A
authors.initials: A
authors.lastname: Zanella
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis / Q000276:immunology*; D000917:Antibody Formation; D015551:Autoimmunity; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins; D011043:Pokeweed Mitogens / Q000494:pharmacology; D012016:Reference Values; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D007074:Immunoglobulin G; D010835:Phytohemagglutinins; D011043:Pokeweed Mitogens; D013755:Tetradecanoylphorbol Acetate