Human graft-versus-host disease (GVHD) biology beyond 3 months after hematopoietic stem cell transplantation (HSCT) is complex. The Applied Biomarker in Late Effects of Childhood Cancer study (ABLE/PBMTC1202, NCT02067832) evaluated the immune profiles in chronic GVHD (cGVHD) and late acute GVHD (L-aGVHD). Peripheral blood immune cell and plasma markers were analyzed at day 100 post-HSCT and correlated with GVHD diagnosed according to the National Institutes of Health consensus criteria (NIH-CC) for cGVHD. Of 302 children enrolled, 241 were evaluable as L-aGVHD, cGVHD, active L-aGVHD or cGVHD, and no cGVHD/L-aGVHD. Significant marker differences, adjusted for major clinical factors, were defined as meeting all 3 criteria: receiver-operating characteristic area under the curve ≥0.60, P ≤ .05, and effect ratio ≥1.3 or ≤0.75. Patients with only distinctive features but determined as cGVHD by the adjudication committee (non-NIH-CC) had immune profiles similar to NIH-CC. Both cGVHD and L-aGVHD had decreased transitional B cells and increased cytolytic natural killer (NK) cells. cGVHD had additional abnormalities, with increased activated T cells, naive helper T (Th) and cytotoxic T cells, loss of CD56bright regulatory NK cells, and increased ST2 and soluble CD13. Active L-aGVHD before day 114 had additional abnormalities in naive Th, naive regulatory T (Treg) cell populations, and cytokines, and active cGVHD had an increase in PD-1− and a decrease in PD-1+ memory Treg cells. Unsupervised analysis appeared to show a progression of immune abnormalities from no cGVHD/L-aGVHD to L-aGVHD, with the most complex pattern in cGVHD. Comprehensive immune profiling will allow us to better understand how to minimize L-aGVHD and cGVHD. Further confirmation in adult and pediatric cohorts is needed.
Background Despite all recent health-related improvements, anemia remains an extensive global public health issue affecting the lives of about one-fourth of the world population in a geographically heterogeneous pattern. We, therefore, aimed to illustrate the prevalence, severity, most common types, and major determinants of anemia among adults in Khuzestan, Iran, from 2016 to 2019. Methods In a large population-based cross-sectional study comprising of a diverse population, each participant underwent a questionnaire-based interview and laboratory testing for hematological analysis. A hemoglobin (HGB) concentration of < 12 g/dL in non-pregnant women and < 13 g/dL in men were defined anemic. The multivariate logistic regression analysis was performed to explore the association between anemia and its potential determinants. Results Data on 29,550 (96.87%) males and non-pregnant females between 20–65 years of age (mean age: 41.90 ± 11.88 years; female sex: 63.58%; Arab ethnicity: 48.65%), whose HGB level was available, were included in the study. The mean ± SD HGB concentration was 13.75 ± 1.65 g/dL. The age- and sex-standardized prevalence rate of anemia was 10.86% (95% CI: 10.51–11.23%). The most prevalent degree was mild anemia (7.71%, 95% CI: 7.40–8.03%) and only 0.17% were severely anemic. Of those considered anemic, the highest proportion was related to normochromic/microcytic (50.65%), followed by hypochromic/microcytic (30.29%). In the multiple logistic regression, the parameters of female gender (OR: 3.17, 95% CI: 2.68–3.76), age group of 35–49 years (OR: 1.66, 95% CI: 1.52–1.82), being underweight (OR: 1.58, 95% CI: 1.29–1.93), being unemployed or retired (OR: 1.55, 95% CI: 1.33–1.81), and living in urban areas (OR: 1.18, 95% CI: 1.09–1.29) were major determinants of anemia. Additionally, we observed a minor but significant positive association between anemia status and CKD, older ages, increased night sleep duration, being a housewife and married, as well as a negative association between anemia and factors including hookah smoking, presence of metabolic syndrome, and overweight and obesity. Conclusions Taken together, the anemia prevalence in this study population was of mild public health significance. The major suspected causes might be iron deficiency and chronic disease anemias. Comparably higher rates of anemia were observed amongst women, individuals aged 35–49 years, underweights, unemployed or retired subjects, and urban residents.
The demand for standard platelet concentrates (PCs) has continued to increase in the recent years. Infusible platelet membranes (IPM) prepared from new or outdated human platelets have been developed as an alternative to standard PCs, with the additional advantage of long shelf life and increased viral safety. Reduction of HLA antigens on the IPM has been assigned as one of the probable advantages of this product. In re-examining this issue, we studied the existence of HLA class I on the surface of IPM microparticles. In comparison we also surveyed HLA expression on the surface of the naturally occurred platelet-derived microparticles (nPMPs) during 7 days storage. Intended for producing IPM, PCs obtained from Iranian blood transfusion organization were lysed; virally inactivated with wet heat in the presence of a heat stabilizer and then sonicated. IPMs were separated using centrifugation and liquid-stored in 4°C. The expression of HLA class I antigens was surveyed using flow cytometry technique. HLA molecules were present on the microparticles. Shedding of HLA antigens was demonstrated from the surface of the both liquid-stored IPM and nPMPs during storage. Storage of IPM in 4°C was accompanied with significant reduction of HLA molecules. It seemed that achievement of HLA-free IPM could be impossible unless chloroquine treated platelets were used to prepare these microvesicles.
Chronic graft-versus-host disease (cGvHD) is a major cause of morbidity after Hematopoietic Stem Cell Transplantation (HSCT). In large patient populations, we have shown a CD56bright Natural Killer population to strongly associate with a lack of cGvHD and we hypothesize that these cells function to suppress cGvHD. We aimed to isolate and define the characteristics of NKreg cells associated with suppression of cGvHD. Immunophenotypic evaluation of a large pediatric population found the CD56bright NK population associated with a lack of cGvHD to be perforin-, Granzyme B-, and CD335+. Transcriptome analysis of a small patient cohort of CD56bright compared to CD56dim NK cells found the NKreg cells to also overexpress Granzyme K, IL-7R, GPR183, RANK, GM-CSFR, TCF7, and IL23A. Further analysis of this CD56bright NKreg population found a subpopulation that overexpressed IRF1, and TNF. We also found that viable NKreg cells may be isolated by sorting on CD56+ and CD16- NK cells, and this population can suppress allogeneic CD4+ T cells, but not Treg cells or CD8+ T cells through a non-cytolytic, cell-cell contact dependent mechanism. Suppression was not reliant upon the NKp44, NKp46, or GPR183 receptors. Additionally, NKreg cells do not kill leukemic cells. Moreover, this is the first paper to clearly establish that a CD56brightCD3-CD16-perforin- NKreg population associates with a lack of cGvHD and has several unique characteristics, including the suppression of helper T cell function in vitro. With further investigation we may decipher the mechanism of NKreg suppression and operationalize expansion of NKreg cells associated with cGvHD suppression.
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