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Introduction: Circulating microparticles (MP) are being described as potential biomarkers for disease activity in a variety of conditions including sickle cell anemia (SCA). However, relatively little is known about the influence of spleen status on MP levels in patients with SCA. Methods: Using a prospective study design we characterize circulating MP in 144 patients with SCA in steady state by assessing their cellular origin and their relationships to spleen status defined by clinical and imaging findings. In addition, MP levels were studied according to demographic characteristics, clinical status, treatment modalities, and other hematological and biochemical parameters. Absolute plasma concentrations of MP were determined by flow cytometry. Results: Patients with SCA displayed a 10‐fold increase in levels of MP derived from red blood cell (RBC) and platelets (PLT) when compared to their healthy counterparts (p < 0.0001). Splenectomized patients with SCA have more pronounced levels of MPRBC and MPPLT, and remained elevated after several weeks of follow‐up. Levels of MP were not significantly associated with spleen removal procedures, age, gender, clinical severity score, hydroxyurea therapy, hemoglobin F, and co‐existence of glucose‐6‐phosphate dehydrogenase deficiency. Conclusion: Collectively, these results suggest that splenectomy affects circulating levels of MP regardless of the known SCA modifiers and correlates. [ABSTRACT FROM AUTHOR]

Background: Even with the most reliable automated blood cell analyzers, obtaining an accurate platelet count in patients with thrombocytopenia is still challenging especially when making decisions for platelet transfusions. The Cell-Dyn Sapphire offers three methods for platelet counting including the optical, impedance, and immunological techniques. Aim: A comparative analysis evaluating the performance of these three methods, along with the manual technique, was performed in thrombocytopenic patients. Materials and Methods: A total of 32 blood samples from patients without a history of chemotherapy and a platelet count

Loss of memory B cells occurs from the onset of HIV-1 infection and persists into the chronic stages of infection. Lack of survival of these cells, even in subjects being treated, could primarily be the consequence of an altered local microenvironment induced by HIV infection. In this study we showed that memory B cell survival was significantly decreased in aviremic successfully treated (ST) subjects compared with subjects who control viral load as a result of natural immunity (elite controller [EC]) or with uninfected control [(HIV.sup.-]) subjects. The lower survival levels observed in memory B cells from ST subjects were the result of disrupted IL-2 signaling that led to increased transcriptional activity of Foxo3a and increased expression of its proapoptotic target TRAIL. Notably, memory B cell survival in ST subjects was significantly enhanced by the addition of exogenous IL-2 in a Foxo3a-dependent manner. We further showed that Foxo3a silencing by siRNA resulted in decreased expression of TRAIL and apoptosis levels in memory B cells from ST subjects. Our results thus establish a direct role for Foxo3a/TRAIL signaling in the persistence of memory B cells and provide a mechanism for the reduced survival of memory B cells during HIV infection. This knowledge could be exploited for the development of therapeutic and preventative HIV vaccines., Introduction In addition to progressive T cell dysfunction and cell death, HIV infection itself leads to early and profound deregulation of B cell physiology, homeostasis, and function. These are manifested [...]

HIV persists in a reservoir of latently infected [CD4.sup.+] T cells in individuals treated with highly active antiretroviral therapy (HAART). Here we identify central memory ([T.sub.CM]) and transitional memory ([T.sub.TM]) [CD4.sup.+] T cells as the major cellular reservoirs for HIV and find that viral persistence is ensured by two different mechanisms. HIV primarily persists in [T.sub.CM] cells in subjects showing reconstitution of the [CD4.sup.+] compartment upon HAART. This reservoir is maintained through T cell survival and low-level antigen-driven proliferation and is slowly depleted with time. In contrast, proviral DNA is preferentially detected in [T.sub.TM] cells from aviremic individuals with low [CD4.sup.+] counts and higher amounts of interleukin-7-mediated homeostatic proliferation, a mechanism that ensures the persistence of these cells. Our results suggest that viral eradication might be achieved through the combined use of strategic interventions targeting viral replication and, as in cancer, drugs that interfere with the self renewal and persistence of proliferating memory T cells., Treatment of HIV infection has markedly reduced the death rate from AIDS and improved the quality of life of HIV-infected individuals (1). However, complete eradication of HIV with antiretroviral drugs [...]

The persistence of central memory [CD4.sup.+} T cells ([T.sub.CM] cells) is a major correlate of immunological protection in HIV/AIDS, as the rate of [T.sub.CM] cell decline predicts HIV disease progression. In this study, we show that [T.sub.CM] cells and effector memory [CD4.sup.+} T cells ([T.sub.EM] cells) from [HIV.sup.+] elite controller (EC) subjects are less susceptible to Fas-mediated apoptosis and persist longer after multiple rounds of T cell receptor triggering when compared to [T.sub.CM] and [T.sub.EM] cells from aviremic successfully treated (ST) subjects or from [HIV.sup.-] donors. We show that persistence of [T.sub.CM] cells from EC subjects is a direct consequence of inactivation of the FOXO3a pathway. Silencing the transcriptionally active form of FOXO3a by small interfering RNA or by introducing a FOXO3a dominant-negative form (FOXO3a Nt) extended the long-term survival of [T.sub.CM] cells from ST subjects to a length of time similar to that of [T.sub.CM] cells from EC subjects. The crucial role of FOXO3a in the survival of memory cells will help shed light on the underlying immunological mechanisms that control viral replication in EC subjects., Successful immune responses induce long-lasting protection, which is primarily characterized by the persistence of functional memory [CD4.sup.+} T cells, especially the [T.sub.CM] cell subset (1-3). Previous studies in humans and [...]

Author(s): Lydie Trautmann [1, 2, 3]; Loury Janbazian [1, 4, 8]; Nicolas Chomont [1, 2, 3, 8]; Elias A Said [1, 2, 3]; Sylvain Gimmig [1]; Benoit Bessette [1]; Mohamed-Rachid [...]

Abstract Background Elite controllers (EC) are a rare subset of HIV infected individuals who control viral load below 50 copies/ml of plasma without treatment. Methods Thirty four EC were studied. The slope of CD4 count change was available for 25 of these subjects. We assessed immune activation by measuring the percent of CD38+HLA-DR+CD8+ T cells in the EC group and comparing it with that in 24 treatment-naïve HIV disease progressors and 13 HIV uninfected healthy controls. Results Compared to HIV uninfected subjects, EC had higher percentages of CD38+HLA-DR+CD8+ T cells (p < 0.001) that was lower than that observed in progressors (p < 0.01). Fifteen of 25 EC had a slope of CD4 count change that was not significantly different from 0 while 3 had a positive and 7 a negative CD4 count slope. Immune activation did not distinguish EC subsets with stable/increasing versus declining CD4 counts. Conclusions Elevated immune activation in ECs is not associated with a faster rate of CD4 decline

Due to their immunoregulatory properties, several specialized cell subsets, including regulatory T (Treg), invariant natural killer T (iNKT) and regulatory B (Breg) cells, are involved in the pathogenesis of non-Hodgkin lymphoma (NHL). However, the interaction between various cells remains to be elucidated. The aim of the present study was to evaluate the levels of Treg, iNKT and Breg cell subsets and their interrelationships in the peripheral blood (PB) and bone marrow (BM) of patients with B-cell NHL who received rituximab-based regimens and achieved a complete remission. A total of 20 patients and 20 healthy age- and sex-matched controls were prospectively enrolled for investigation of Treg, iNKT and Breg cell subsets in PB and BM by flow cytometry and cell culture. Prior to administration of combination chemotherapy with rituximab, the patients had lower levels of Breg cells and, to a lesser degree, Treg cells, but not iNKT cells, in PB compared with controls. Compartmental differences in the levels of Treg and Breg cell subsets, but not iNKT cells, were observed between PB and BM, suggesting an increase in trafficking through the blood of these regulatory cell subsets to the marrow. Following complete remission, the levels of circulating Treg, iNKT and Breg cell subsets increased. The levels of Treg cells were not significantly associated with iNKT and Breg cell subsets, although negative correlations were observed. Taken together, these results may provide new insights into the potential role of regulatory cell subsets in patients with B-cell NHL. However, whether the observed differences between PB and BM may affect clinical outcomes requires further investigation. [ABSTRACT FROM AUTHOR]