KIR2DS3 is associated with protection against acute myeloid leukemia

Background: Interaction between killer cell immunoglobulin-like receptors (KIR) and human leukocyte antigen (HLA) class I molecules is important for regulation of natural killer (NK) cell function. Objective: The aim of this study was to investigate the impact of compound KIR-HLA genotype on susceptibility to acute leukemia. Methods: Cohorts of Iranian patients with acute myeloid leukemia (AML; n=40) and acute lymphoid leukemia (ALL; n=38) were genotyped for seventeen KIR genes and their three major HLA class I ligand groups (C1, C2, Bw4) by a combined polymerase chain reaction-sequence-specific primers (PCR-SSP) assay. The results were compared with those of 200 healthy control individuals. Results: We found a significantly decreased frequency of KIR2DS3 in AML patients compared to control group (12.5 vs. 38, odds ratio=0.23, p=0.0018). Also, the KIR3DS1 was less common in AML group than controls (27.5 vs. 44.5, p=0.0465, not significant after correction). Other analyses including KIR genotypes, distribution and balance of inhibitory and activating KIR+HLA combinations, and coinheritance of activating KIR genes with inhibitory KIR+HLA pairs were not significantly different between leukemia patients and the control group. However, in AML patients a trend toward less activating and more inhibitory KIR-HLA state was observed. Interestingly, this situation was not found in ALL patients and inhibition enhancement through increase of HLA ligands and inhibitory combinations was the main feature in this group. Conclusion: Our findings may suggest a mechanism for escape of leukemic cells from NK cell immunity

Increased activation and expansion of a CD57+ subset within peripheral CD8+ T lymphocytes in mycobacterium tuberculosis-infected patients

Background: Mycobacterium tuberculosis-specific CD8+ and CD4+ T lymphocyte responses restrict the spread of extracellular pathogens by limiting M. tuberculosis replication. Alterations in cytolytic function, inappropriate maturation/differentiation, and limited proliferation could reduce their ability to control M. tuberculosis replication. Methods: In an attempt to further characterize the immune responses during M.tuberculosis infection, we enumerated γδ and αβ receptor-bearing T cells expressing CD8 or CD4 phenotype and analyzed the differentiation phenotypes of CD8+ and CD4+ T lymphocyte subpopulations in 47 cases (23 new cases and 24 multidrug resistant patients) and 20 control subjects, using flowcytometry. Results: We found that the CD4/CD8 ratio was significantly lower in newly-diagnosed M.tuberculosis patients compared to multidrug resistant and control subjects (P < 0.003). Also, we found that a large proportion of CD8+ T lymphocytes in newly-diagnosed patients was defined by increased surface expression of CD57 as compared to the two other settings (P < 0.002). This increase was more profound in patients with an inverted CD4/CD8 ratio. Analysis of the late activation antigen revealed that this was predominantly HLA-DR+ (P < 0.003). No significant changes were observed in the percentages of CDB+CD57+ T cells between the different settings. Moreover, the co-stimulatory molecule CD28+ tended to be underexpressed by CD8+ T cells in multidrug resistant patients when compared to newly-diagnosed subjects (P < 0.002), but not to the control subjects. In contrast, the frequency of CD28+ marker on CD4+ T cells was higher in the setting of multidrug resistant compared with those of new cases (P < 0.0001). No significant changes were observed in percentages of γδ receptor-bearing T cells between different groups. Conclusion: We suggest that the increase in the proportion of CD57+ within CD8+ T cells in newly-diagnosed patients results from M.tuberculosis antigenic stimulation, which is a hallmark of many infections and that the protracted accumulation of CD57+ T lymphocytes might reflect an end-stage differentiation phenotype

Local eosinophils are associated with increased IgA subclass levels in the sinonasal mucosa of chronic rhinosinusitis with polyp patients

Background: Chronic rhinosinusitis (CRS) describes an inflammatory condition affecting the sinonasal mucosa. As the immune system players such as immunoglobulins play prominent roles in the development of CRS, we aimed to investigate the expression of IgA subclasses and factors involved in IgA class switching in the sinonasal mucosa of CRS patients. Methods: Specimens were collected from the sinonasal mucosa of the healthy controls and CRS patients. Histological assessments were performed by H&E and immunohistochemistry. Real-time PCR and ELISA methods were applied to measure gene expression and protein levels extracted from tissue samples, respectively. Results: We observed that total IgA and subclass-positive cells were higher in the patient groups than controls. There was a significant correlation between the number of eosinophils and total IgA and subclasses-positive cells (Pv < 0.0001). The expression of CXCL13, BAFF, AID, and germline transcripts were increased in CRSwNP patients. In contrast to IgA2 levels, IgA1 levels were significantly increased in the sinonasal tissue of CRSwNP patients (Pv < 0.01). TGF-β was significantly elevated in the sinonasal tissue of patients with CRSsNP. Conclusions: Increased protein levels of IgA subclasses and related antibody-producing cells were associated with elevated eosinophils in CRSwNP patients which may result in eosinophil pathological functions. Several therapeutic approaches might be developed to modulate the IgA production to ameliorate the inflammatory mechanisms in CRSwNP patients.Figure not available: see fulltext. © 2020 The Author(s)