Alloimmunization in patients with sickle cell disease in French Guiana.

This study in French Guiana assessed the frequency of alloimmunization to red cell antigens in sickle cell disease patients over 1995-2011 and identified the most common antibodies. A retrospective analysis of the transfusion history and medical records of 302 patients showed that 29/178 transfused patients had developed alloantibodies (16%). The most frequent alloantibodies were anti-LE1, anti-MNS1, anti-LE2, and anti-FY1 and were developed after transfusion of standard red cell units. The frequency of the clinically significant antibodies in this population of SCD patients was 11% (19/178). The antibodies found on those patients who had delayed hemolytic transfusion reaction were anti-K1, anti-FY1, and anti-MNS3. The strategies used to decrease alloimmunization in French Guiana are discussed.

Dual mechanism of impairment of interleukin-7 (IL-7) responses in human immunodeficiency virus infection: decreased IL-7 binding and abnormal activation of the JAK/STAT5 pathway.

Interleukin-7 (IL-7) plays a central role in controlling the homeostasis of both naive and long-term-memory CD4(+) T cells. To better understand how human immunodeficiency virus (HIV) perturbs CD4(+) T-cell homeostasis, we performed a detailed analysis of IL-7R expression, IL-7 binding, and IL-7-dependent early and late signaling events in CD4(+) T-cell subsets from viremic and efficiently treated patients. HIV infection differentially affected the expression of IL-7 receptor (IL-7R) chains, with decreases in IL-7Ralpha/CD127 expression in the memory subset and increases in gammac/CD132 expression in all CD4(+) T cells. This resulted in preserved IL-7 binding in the naive compartment and decreased IL-7 binding in the memory compartment of viremic patients. Accordingly, the percentages of cells signaling in response to IL-7, as measured by pSTAT5 induction, were decreased in memory subsets, including conventional CD4(+) T cells and regulatory T cells. However, the levels of pSTAT5 induction per responding cell, as measured by pSTAT5 fluorescence intensity, were increased within all naive and memory CD4(+) T-cell subsets of viremic patients. The basal level of pSTAT5 was also increased, indicating a constitutive activation of the JAK/STAT5 pathway. IL-7 functional responses, as measured by Bcl-2, CD25, and Foxp3 induction, were impaired in viremic patient CD4(+) T cells, suggesting that chronic activation led to downstream defects in the STAT5 signaling pathway. Thus, HIV infection perturbs IL-7 responses at both receptor binding and signaling steps, which likely compromises the regenerative capacity of the CD4(+) T-cell pool and may contribute to CD4(+) T-cell depletion.