In vitro production of anti‐RBC antibodies and cytokines in chronic lymphocytic leukemia

Barcellini, Wilma; Montesano, Rosanna; Clerici, Giacomo; Zaninoni, Anna; Imperiali, Francesca Guia; Calori, Rossella; Cortelezzi, Agostino; Zanella, Alberto

doi:10.1002/ajh.10210

Cited by 32 publications

(15 citation statements)

References 36 publications

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“…Mitogen-stimulated DAT (MS-DAT) is another technique that can be used to diagnose the presence of latent anti-red cell antibodies. Barcellini et al (2002) reported 28AE9% prevalence of anti-red cell antibodies by using MS-DAT while conventional DAT was positive in only 4AE3% patients. Use of rituximab in FCR may be the factor that contributes to the masking of DAT positivity.…”

Section: Discussionmentioning

confidence: 97%

Immune anaemias in patients with chronic lymphocytic leukaemia treated with fludarabine, cyclophosphamide and rituximab – incidence and predictors

et al. 2007

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Immune anaemias (IA) [auto-immune haemolytic anaemia (AIHA) and pure red cell aplasia (PRCA)] are complications of chronic lymphocytic leukaemia (CLL). Fludarabine has been associated with AIHA, whereas both rituximab and cyclophosphamide have been used to treat this condition. Combining these agents with fludarabine may reduce the likelihood of AIHA. We report on the incidence, outcome and pretreatment predictors of IA in 300 patients treated with fludarabine, cyclophosphamide and rituximab (FCR). Nineteen patients (6AE5%) developed IA [AIHA (5AE8%), PRCA (0AE7%)] on or after treatment with FCR. Most patients (82AE4%) with AIHA had a negative direct antiglobulin test (DAT). Additional markers of haemolysis (indirect hyperbilirubinaemia, reticulocytosis, low haptoglobin and elevated lactate dehydrogenase levels) confirmed the presence of AIHA in these patients. The majority of patients responded to therapies including steroids, ciclosporin, i.v. immunoglobulin, etc. High pretreatment levels of beta-2 microglobulin predicted for development of IA. No haemolytic crisis was observed during FCR therapy in eight patients with AIHA prior to FCR. Thus, the incidence of IA among CLL patients treated with FCR was comparable with historical rates. The diagnosis of AIHA can be considered even if the DAT is negative. Pre-existing AIHA need not preclude front-line FCR therapy.

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Section: Discussionmentioning

confidence: 97%

Immune anaemias in patients with chronic lymphocytic leukaemia treated with fludarabine, cyclophosphamide and rituximab – incidence and predictors

et al. 2007

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“…The quantification of anti-RBC-bound IgG in mitogenstimulated cultures was evaluated with MS-DAT, as previously described [9,11]. Fresh heparinized blood samples were diluted 1:6 with RPMI 1640 medium (Gibco) and either stimulated or not stimulated with mitogens (2 lg/ml phytohemagglutinin (PHA), 20 ng/ml phorbol miristate acetate (PMA), or 1% pokeweed (PWM, Sigma, St. Louis, MO, USA) in 24-well plates for 48 h. RBCs were washed four times with phosphate-buffered saline (PBS), centrifuged at 1,000 rpm for 10 min, resuspended in PBS at 10% concentration, and processed for the quantitation of antiautologous RBC-bound IgG.…”

Section: Anti-rbc-bound Igg Quantification By Ms-datmentioning

confidence: 99%

“…More recently, mitogen-stimulated (MS)-DAT has been proposed as a functional and quantitative method for the detection of anti-RBC antibodies in mitogen-stimulated whole-blood cultures; the test could identify cytokine modulation of anti-RBC antibody production in AIHA [9], and facilitated the diagnosis of some DAT-negative AIHA cases [10]. Moreover, MS-DAT was found to be positive in a fraction of B-chronic lymphocytic leukemia (B-CLL) patients without an overt diagnosis of AIHA, suggesting that in vitro mitogen stimulation could be used to identify latent anti-RBC autoimmunity in B-CLL [11].…”

Section: Introductionmentioning

confidence: 99%

Comparison of traditional methods and mitogen-stimulated direct antiglobulin test for detection of anti-red blood cell autoimmunity

et al. 2010

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The diagnosis of autoimmune hemolytic anemia (AIHA) is based on a positive direct antiglobulin test (DAT), which is performed using various methods with different sensitivities. Recently, mitogen-stimulated (MS)-DAT was suggested to be able to identify latent anti-erythrocyte autoimmunity. Traditional methods (tube, microcolumn, and solid phase) and MS-DAT were compared in 54 consecutive cases of suspected AIHA, 28 idiopathic AIHA in clinical remission, and 12 difficult-to-diagnose cases of DAT-negative AIHA, and the results (all cases) were correlated with hematologic and hemolytic parameters. DAT tube was confirmed as the gold standard to diagnose AIHA since almost all positive cases showed hemolytic anemia and positive eluates; 10 out of 26 tube-negative cases were positive on microcolumn and solid phase antiglobulin tests, and 22 out of 26 using MS-DAT, although only half of them showed clear signs of hemolysis. Mitogen stimulation increased the amount of IgG bound to red blood cells in all groups; moreover, MS-DAT was the only positive test in 10 cases of AIHA, and mitogen stimulation facilitated the identification of autoantibody specificity in culture supernatants. We conclude that a battery of tests rather than a single test is useful for the diagnosis of AIHA, including MS-DAT as an additional test for selected cases, although the results have to be cautiously interpreted based on the overall clinical context.

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“…Análise multivariada revelou que a IL-4 foi significantemente mais elevada, e o IFN-γ foi significantemente mais baixo em pacientes com LLC e TAD positivo. 15 A participação de genes V H na fisiopatologia da AHAI secundária à LLC é questionável. Em estudo com apenas 12 indivíduos com AHAI associada à LLC foi verificada a presença de V 1-69 em cinco e V 3-33 em quatro pacientes, mas em nenhum de 12 indivíduos do grupo controle.…”

Section: Mecanismos Biológicos Da Auto-imunidade Na Llcunclassified

Anemia hemolítica auto-imune e outras manifestações imunes da leucemia linfocítica crônica

Bordin¹

2005

Rev. Bras. Hematol. Hemoter.

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In vitro production of anti‐RBC antibodies and cytokines in chronic lymphocytic leukemia

Abstract: B-chronic lymphocytic leukemia (B-CLL

Cited by 32 publications

References 36 publications

Immune anaemias in patients with chronic lymphocytic leukaemia treated with fludarabine, cyclophosphamide and rituximab – incidence and predictors

Immune anaemias in patients with chronic lymphocytic leukaemia treated with fludarabine, cyclophosphamide and rituximab – incidence and predictors

Comparison of traditional methods and mitogen-stimulated direct antiglobulin test for detection of anti-red blood cell autoimmunity

Anemia hemolítica auto-imune e outras manifestações imunes da leucemia linfocítica crônica

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