Inhibitory killer cell immunoglobulin-like receptor KIR3DL1 in combination with HLA-B Bw4iso protect against Ankylosing spondylitis

Background: The HLA class I molecules serve as ligands for both T cell receptors and killer cell immunoglobulin-like receptors (KIRs). Objective: We investigated the HLA- C and HLA-Bw4 alleles as well as KIRs expression on CD56 positive lymphocytes to evaluate whether these genes and molecules could influence Ankylosing spondylitis (AS) susceptibility, alone or in combination. Methods: We typed 40 AS patients and 40 normal controls for HLA-C asn80 (group 1) and HLA-C lys80 (group 2), HLA-B Bw4thero, HLA-B Bw4iso and HLA-A Bw4 alleles by PCR-SSP method. We also as- sessed the expression of KIR2DL1/2DS1, KIR2DL2/2DL3, KIR3DL1 and KIR2DS4 by flow cytometry. The Pearson chi-square or Fisher exact test was performed for statisti- cal analysis. Results: The frequency of HLA-B Bw4iso but not HLA-B Bw4thero and HLA-A Bw4, ligand for the inhibitory KIR3DL1, was significantly reduced in AS pa- tients as compared with controls (p<0.01). No significant differences were observed in gene carrier frequencies of HLA-C group 1 and 2 between AS and controls. Although no differences were found in the expression of KIR receptors between AS and normal subjects, we found that expression of KIR3DL1 in the presence of HLA Bw4-Biso gene was reduced in patients with AS compared to healthy controls (p<0.009). Conclusion: We conclude that HLA-B Bw4iso, the ligand of inhibitory KIR3DL1, with and without the expression of KIR3DL1 might be involved in protection against AS. Our results suggest that besides the HLA and KIR genotype, expression levels of KIRs may be in- volved in the pathogenesis of AS disease

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

Determination of Serum Levels of Interleukin-6, Interleukin-8, Interleukin-10, and Tumor Necrosis-Alpha and their Relationship With The Total Body Surface Area in Children

There are few studies on the inflammatory processes and the role of cytokines involved in pediatric burn injuries. The present study aims to measure the serum levels of cytokines and their relationship with the degree of burn injury in children. Within the 48 hours of hospitalization, the serum samples were obtained to measure inflammatory cytokines (interleukin-6, interleukin-8, interleukin-10 IL-6, IL-8, and IL-10 and tumor necrosis factor-alpha TNF-α). The level of all of these cytokine factors was assessed by enzyme-linked immunosorbent assay technique. The mean levels of IL-6, IL-8, IL-10, and TNF-α was 18.15 ± 4.77 pg/ml, 59.54 ± 4.59 pg/ml, 8.41 ± 2.09 pg/ml, and 1.48 ± 0.15 pg/ml, respectively, which were higher than the normal range designated for the healthy pediatrics age group. The levels of TNF-α were higher in patients with sepsis (P = .03) and deceased patients (P = .001). There was a statistically significant difference in the levels of IL-8 in patients with second- (.001) and third-degree (.001) burn injuries in comparison to the first-degree burn injuries, and the level of IL-8 was statistically significantly higher in patients with electrical burn injuries in comparison to scald burn injuries (.01). IL-10 was statistically significantly higher in patients with contact burn injuries in comparison to scald (.001) and flame (.03) burn injuries. Cytokine levels in pediatric burn patients increased after severe burn injuries. There was a significant correlation between the levels of IL-8 and the degree of burn injuries. © American Burn Association 2019. All rights reserved. For permissions, please e-mail: [email protected]

Detection of Antisperm Antibodies by Indirect Flow Cytometry: Comparison with Direct Mixed Agglutination Reaction Test

Background and Objectives: The immunobead binding test (IBT) and the mixed agglutination reaction (MAR) are the most commonly used methods for detection of antisperm antibodies (ASA). The detection of ASA by flow cytometry (FCM) was first described by Haas and Cunningham. Both assays can be performed as direct or indirect methods. In this study, indirect FCM was compared with the direct MAR for detection of ASA. Methods: Semen samples were obtained from 80 men (infertile couples) in Isfahan Fertility and Infertility Center. Seminal plasma samples were incubated with ASA-negative donor sperm. Then, surface-bound antibody was detected with FITC-labeled antihuman immunoglobulin directed against IgA and IgG in the indirect FCM assay. ASAs bound to the surface of patients’ sperm were detected by direct MAR test. Results: The indirect FCM correlates with direct MAR for detection of IgA antisperm antibodies (r=0.55 and P=0.006). The indirect FCM, however, does not correlate with direct MAR for the detection of IgG antisperm antibodies (r=0.25 and P=0.25). Conclusion: Some of the ASAs in seminal fluid bind to spermatozoa. Therefore, indirect tests to detect ASAs in seminal plasma are likely to miss the presence of IgG antisperm antibodies while they effectively detect IgA antisperm antibodies. Keywords: Antisperm Antibody; Agglutination; Flow Cytometry; Sperm Agglutinatio