[Infections in patients with acute myeloid leukemia]. / Infektionen bei Patient*innen mit Akuter Myeloischer Leukämie.

Infections represent one of the most frequent complications during therapy of acute myeloid leukemia (AML). In addition to associated prolonged phases of neutropenia, damage to the mucosal barrier by cytotoxic agents favors infections caused by endogenous pathogens. The source often remains unknown with bacteremia being the most common evidence of infection. Infections with gram-positive bacteria predominate, however, infections with gram-negative bacteria more often lead to sepsis and death. Due to prolonged neutropenia, patients with AML are furthermore at risk for invasive fungal infections. Viruses, on the other hand, are rarely the cause of neutropenic fever. Because of the limited inflammatory response in neutropenic patients, fever is often the only sign of infection and therefore always represents a hematologic emergency. Prompt diagnosis and initiation of an adequate anti-infective therapy are critical to avoid progression to sepsis and possibly death.

[Autoimmune haemolytic anemias]. / Autoimmunhämolytische Anämien.

Autoimmune haemolytic anemia (AIHA) is defined as the immune-mediated destruction of red blood cells. In most cases, antibodies that target surface antigens on erythrocytes lead to their premature degradation in the spleen or, less commonly, in the liver. The term includes a heterogenous group of diseases, which differ largely in pathophysiology and treatment. The two most common entities are warm AIHA and cold AIHA. Diagnostic testing involves the analysis of haemolytic markers like lactate dehydrogenase, haptoglobin and unconjugated bilirubin as well as a hemoglobin and reticulocytes. In case of a haemolytic anemia, further testing like a blood smear and a direct antiglobulin test should follow. As diagnostic testing and treatment of AIHA are complex, affected patients should always be referred to a hematologist.In warm AIHA, mainly IgG autoantibodies bind to their antigen on the erythrocyte surface at body temperature, leading to their premature destruction in the spleen. First line treatment options include the administration of steroids which mitigate the destruction of red blood cells by macrophages in the spleen. In contrast, IgM autoantibodies in cold AIHA lead to intravasal agglutination of erythrocytes and complement activation. The IgM antibodies have their highest affinity below body temperature which is why patients experience symptoms mainly in cold-exposed body areas. Although the IgM antibodies dissolve at body temperature, the complement-loaded erythrocytes are destroyed in the liver. Therapeutic options include protection from cold and immunosuppressive agents or complement inhibition.

Th1-Biased Hepatitis C Virus-Specific Follicular T Helper-Like Cells Effectively Support B Cells After Antiviral Therapy.

Circulating Th1-biased follicular T helper (cTfh1) cells have been associated with antibody responses to viral infection and after vaccination but their B cell helper functionality is less understood. After viral elimination, Tfh1 cells are the dominant subset within circulating Hepatitis C Virus (HCV)-specific CD4 T cells, but their functional capacity is currently unknown. To address this important point, we established a clone-based system to evaluate CD4 T cell functionality in vitro to overcome experimental limitations associated with their low frequencies. Specifically, we analyzed the transcription factor expression, cytokine secretion and B cell help in co-culture assays of HCV- (n = 18) and influenza-specific CD4 T cell clones (n = 5) in comparison to Tfh (n = 26) and Th1 clones (n = 15) with unknown antigen-specificity derived from healthy donors (n = 4) or direct-acting antiviral (DAA)-treated patients (n = 5). The transcription factor expression and cytokine secretion patterns of HCV-specific CD4 T cell clones indicated a Tfh1 phenotype, with expression of T-bet and Bcl6 and production of IFN-γ and IL-21. Their B helper capacity was superior compared to influenza-specific or Tfh and Th1 clones. Moreover, since Tfh cells are enriched in the IFN-rich milieu of the HCV-infected liver, we investigated the impact of IFN exposure on Tfh phenotype and function. Type I IFN exposure was able to introduce similar phenotypic and functional characteristics in the Tfh cell population within PBMCs or Tfh clones in vitro in line with our finding that Tfh cells are elevated in HCV-infected patients shortly after initiation of IFN-α therapy. Collectively, we were able to functionally characterize HCV-specific CD4 T cells in vitro and not only confirmed a Tfh1 phenotype but observed superior Tfh functionality despite their Th1 bias. Furthermore, our results suggest that chronic type I IFN exposure supports the enrichment of highly functional HCV-specific Tfh-like cells during HCV infection. Thus, HCV-specific Tfh-like cells after DAA therapy may be a promising target for future vaccination design aiming to introduce a neutralizing antibody response.