Antibody-dependent cellular cytotoxicity (ADCC) is exerted by immune cells expressing surface Fcγ receptors (FcγRs) against cells coated with antibody, such as virus-infected or transformed cells. CD16, the FcγRIIIA, is essential for ADCC by NK cells, and is also expressed by a subset of human blood monocytes. We found that human CD16− expressing monocytes have a broad spectrum of ADCC capacities and can kill cancer cell lines, primary leukemic cells and hepatitis B virus-infected cells in the presence of specific antibodies. Engagement of CD16 on monocytes by antibody bound to target cells activated β2-integrins and induced TNFα secretion. In turn, this induced TNFR expression on the target cells, making them susceptible to TNFα-mediated cell death. Treatment with TLR agonists, DAMPs or cytokines, such as IFNγ, further enhanced ADCC. Monocytes lacking CD16 did not exert ADCC but acquired this property after CD16 expression was induced by either cytokine stimulation or transient transfection. Notably, CD16+ monocytes from patients with leukemia also exerted potent ADCC. Hence, CD16+ monocytes are important effectors of ADCC, suggesting further developments of this property in the context of cellular therapies for cancer and infectious diseases.
Introduction A high incidence of mortality and severe COVID‐19 infection was reported in hematopoietic stem cell transplant (HSCT) recipients during the early phases of the COVID‐19 pandemic; however, outcomes with subsequent severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants, such as the omicron variant, have yet to be reported. Additionally, rollout of COVID‐19 vaccinations in subsequent pandemic waves may modify COVID‐19 disease severity and mortality in this immunocompromised population. We describe COVID‐19 outcomes among a highly vaccinated population of HSCT recipients at a single center during successive waves of community transmission arising from the SARS‐CoV‐2 delta and omicron variants. Methods We retrospectively reviewed medical records of all HSCT recipients at our institution who tested positive for SARS‐CoV‐2 from May 2021 to May 2022. Descriptive statistics were reported; the chi‐square test was utilized to identify factors associated with 90‐day all‐cause mortality and severity of COVID‐19 infection. Results Over the 1‐year study period, 77 HSCT recipients at our center contracted COVID‐19 (43 allogenic; 34 autologous). Twenty‐six (33.8%) patients were infected with the SARS‐CoV‐2 delta variant, while 51 (66.2%) had the SARS‐CoV‐2 omicron variant. Thirty‐nine (50.6%) patients required hospitalization. More than 80% had received prior COVID‐19 vaccination (57.1% with two doses, 27.3% with three doses). The majority (90.9%) had mild disease; only one (1.3%) patient required mechanical ventilation. Active hematological disease at time of COVID‐19 infection was associated with increased odds of mortality [odds ratio (OR) = 6.90, 95% confidence interval (CI) = 1.20–40]. The 90‐day all‐cause mortality was 7.8% (six patients). Infection with the omicron variant (vs. delta) was associated with less severe illness (OR = 0.05, 95% CI = 0.01–0.47) and decreased odds of mortality (OR = 0.08, 95% CI = 0.01–0.76). Being on immunosuppression (OR = 5.10, 95% CI = 1.10–23.60) and being unvaccinated at disease onset (OR = 14.76, 95% CI = 2.89–75.4) were associated with greater severity of COVID‐19 infection. Conclusion We observed favorable outcomes with COVID‐19 infection in a cohort of vaccinated HSCT patients. The SARS‐CoV‐2 omicron variant was associated with both less severe illness and decreased odds of mortality. As COVID‐19 moves toward endemicity, early access to treatment and encouraging vaccination uptake is crucial in mitigating the challenge of COVID‐19 management among HSCT recipients. Surveillance and assessment of clinical outcomes with new SARS‐CoV‐2 variants also remains important in this immunocompromised population.
BACKGROUND Hemolysis at the time of graft infusion is one of the immediate complications in major ABO‐incompatible allogeneic hematopoietic stem cell transplants (HSCTs). We conducted a retrospective analysis to evaluate the efficacy of donor‐type fresh frozen plasma (FFP) in reducing isohemagglutinin titer and preventing hemolysis, as well as its effect on delayed red cell engraftment. MATERIALS AND METHODS This is a single‐center study on a series of 380 allogeneic HSCT between 2005 and 2015; of which 99 were either major (n = 74) or bidirectional (n = 25) ABO mismatched. Pre‐transplant infusion of FFP, post‐transplant complications and transfusion requirements were determined by retrospective review of individual medical records. Laboratory results were also reviewed for evidence of hemolysis and pure red cell aplasia (PRCA). RESULTS Clinical manifestation of hemolysis attributable to ABO mismatch was present in one recipient of major ABO‐incompatible peripheral blood stem cell (PBSC) with a titer of 64. Another recipient of major ABO‐incompatible PBSC with a titer of 64 showed biochemical evidence of hemolysis. Both patients recovered with supportive treatment. Hemolysis did not occur in any patients with titer of 32 or less at the time of stem cell infusion. We were unable to demonstrate the influence of any variables on the incidence of PRCA. CONCLUSION Our experience demonstrated that donor‐type FFP is safe and effective in preventing acute hemolysis in major ABO‐mismatched HSCT. We have also established the titer of 64 as the threshold that may cause hemolysis and therefore efforts should be made to reduce titer to below this level.
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