IL-10 Polymorphisms Research Articles

Effect of IL-2 polymorphism rs2069762 on single-unit cord blood transplant outcomes

BackgroundInterleukin-2 (IL-2) is one of the most important cytokines that regulate the activation and proliferation of T cells and natural killer cells. The production of IL-2 may be affected by polymorphisms in the promoter region of the IL-2 gene (rs2069762). In allogeneic hematopoietic cell transplantation (HCT) from adult donors, rs2069762 has been associated with the incidence of acute and chronic graft-versus-host disease (GVHD). However, the impacts of IL-2 polymorphism on cord blood transplantation (CBT) outcomes remain unclear. ObjectiveThe objective of this study was to assess the impact of IL-2 polymorphism rs2069762 on transplant outcomes, such as hematopoietic recovery, GVHD, overall survival, relapse, and non-relapse mortality (NRM) after CBT. Study DesignWe conducted a retrospective analysis of data from adult patients who underwent single-unit CBT at our institution from November 2005 to March 2023 for whom DNA samples from recipients and donors were available. IL-2 genotyping was performed using real-time polymerase chain reaction with the TaqMan® SNP genotyping assay for rs2069762. ResultsA total of 143 recipient and donor pairs were included in this study. The proportion of recipient IL-2 polymorphism rs2069762 was 48 % (n = 69) for AA, 42 % (n = 60) for CA, and 10 % (n = 14) for CC. The proportion of donor IL-2 polymorphism rs2069762 was 43 % (n = 61) for AA, 48 % (n = 69) for CA, and 9 % (n = 13) for CC. In the multivariate analysis, the use of an rs2069762 CA + CC donor was associated with lower neutrophil recovery compared to an rs2069762 AA donor (hazard ratio [HR], 0.66; 95 % confidence interval [CI], 0.50–0.88; P = 0.004). Furthermore, recipients of rs2069762 CA + CC were associated with higher NRM compared to recipients of rs2069762 AA (HR, 2.32; 95 % CI, 1.01–5.34; P = 0.047). Serum IL-2 levels at 8 weeks were significantly higher in rs2069762 CA + CC recipients compared to those with rs2069762 AA recipients (P = 0.014). ConclusionOur data showed that donor IL-2 polymorphism affects neutrophil recovery and recipient IL-2 polymorphism affects NRM in adults undergoing single-unit CBT. The polymorphism of IL-2 rs2069762 in recipients and donors might be associated with the clinical outcomes of single-unit CBT.

Association of IL-4 polymorphism with severe periodontitis in a sample of Iraqi population.

Specific bacterial plaque and environmental factors cannot be considered the only cause of periodontitis. Still, several genetic factors affect the host response to the bacteria, like gene polymorphisms in anti-inflammatory cytokines. Several studies have reported that clones of T-helper 2 lymphocytes (TH2) are generated in response to dental plaque in periodontitis patients, while in healthy individuals, they are regulated by T-helper 1 (TH1) lymphocytes. Accordingly, such patients consistently produce more IL-4 (TH2) in response to bacterial stimulation, whereas healthy controls with intact periodontal tissues produce a significantly higher level of TH1.

Polymorphism of IL4 and IL13 anti-inflammatory cytokine genes in indigenous populations of the russian Arctic

Living conditions in the Arctic zone are extremely unfavorable for living and contribute to the development of a number of diseases due to suppression of the functions of the immune system. Cytokines are one of the main mediators of the immune system; they are encoded by genes with a high degree of polymorphism. This study examined the distribution of genetic variants in the cytokine genes (rs2243250 IL4, rs1800925 IL13) among the Nenets, Dolgan-Nganasan and Slavs. It was previously established that these mutations are associated with the level of expression of these interleukins and their production, which leads to changes in the impairment of the immune response to the influence of the pathogen. The study showed the predominance of genotypes CT and TT of the rs2243250 IL4 polymorphism, and genotype CC of the rs1800925 IL13 polymorphism in the Nenets and Dolgan-Nganasan populations. The results obtained suggest that the indigenous inhabitants of the Russian Arctic have a genetically determined rapid immune response and protection against the development of allergic diseases compared to the Slavs.

ST2 and IL-33 polymorphisms and the development of childhood asthma: a prospective birth cohort study in Finnish children.

The ST2/IL-33 signaling pathway has an important role in the host inflammatory response. Here we aimed to study the association of ST2 and IL-33 polymorphisms with serum soluble (s) ST2 and IL-33 concentrations in healthy Finnish children and, in addition, their association with childhood asthma. In total, 146 children were followed from birth to the age 7 years for the development of asthma. Single-nucleotide polymorphisms (SNPs) in ST2 and IL-33 were determined, and associations of the SNP variants with serum levels of sST2 and IL-33 at age of 13 months and with recurrent wheezing and childhood asthma at 7 years of age were analyzed. Children with ST2 rs1041973 AC/AA genotypes had significantly lower level of serum sST2 (2453 pg/mL; IQR 2265) than those with CC genotype (5437 pg/mL; IQR 2575; p = < 0.0001). Similar difference was also observed with ST2 rs13408661. No differences were observed between subjects with studied IL-33 SNPs. Children who carried genetic variants of ST2 rs1041973 or rs13408661 seemed to have a higher risk of asthma. In contrast, children who carried genetic variants of IL-33 rs12551268 were less often diagnosed with asthma. Even though these SNPs seemed to associate with asthma, the differences were not statistically significant.

Evaluation of IL-4 and IL-13 Single Nucleotide Polymorphisms and Their Association With Childhood Asthma and Its Severity: A Hospital-Based Case-Control Study.

Asthma is a common, chronic, atopic respiratory disease that is on the rise among children and adults worldwide. Various environmental, genetic, and biological interactions contribute to the surge in susceptibility to this disease. Interleukin (IL) genes, particularly IL-4 and IL-13, have been linked to asthma pathogenesis. The present study aims to investigate the genetic aberrations, specifically single nucleotide polymorphisms (SNPs) of IL-4 and IL-13, and their association with childhood asthma and its severity. An unmatched hospital-based case-control study was conducted in a tertiary care hospital in Assam, India. The sample size was calculated to be 120 (60 cases and 60 controls) using the Epi Info software version 7.2 (Centers for Disease Control and Prevention, Atlanta, GA, USA), assuming a confidence interval of 95%, a power of the study at 80%, a ratio of control to cases as 1, a proportion of controls with exposure at 22%, and a proportion of cases with exposure at 46%. A total of 53 clinically diagnosed cases of childhood asthma in the age range of three to 12 years and 39 healthy controls free from respiratory diseases and having no history of asthma and/or allergy of the same age group attending a tertiary care hospital were included in the study. Children who never had asthma or allergies and who did not suffer from any upper or lower respiratory infections for the previous four weeks were considered controls. Prior informed consent and ethical clearance were obtained. Very seriously ill cases and controls were excluded from the study. The genetic investigation used polymerase chain reaction (PCR), followed by restriction fragment length polymorphism (RFLP), to discover SNPs in the IL-4 and IL-13 genes. Sequencing analysis was done for the cases with +2044 G>A of the IL-13 gene in relation to the severity of the disease. The difference in the proportions of specific SNPs between cases and controls was analyzed using the χ2test (a p-value of <0.05 was considered significant). Both the rs2070874 and rs2243250 polymorphisms of IL-4 showed no statistically significant associations. The mutation of the IL-13 gene in 1111C>T was higher among cases than controls. Both genotypic and allelic distributions of the +2044G>A polymorphism of the IL-13 gene revealed a significant association (p<0.05) with the severity of the disease. Genetic aberrations in SNPs of IL-4 and IL-13 are prevalent among the pediatric patients of the study region. The SNP +2044G>A of IL-13 is instrumental in disease manifestation and severity among the pediatric population of the study region.

The role of cytokine gene polymorphic variants in predicting COVID-19 outcomes

The COVID-19 pandemic has shown that the outcomes of the disease depend on many factors and, above all, genetic mutations in the immune system. A special role in the outcome of COVID-19 is attributed to a defect in the genes of inflammatory cytokines, the excess of which leads to endothelial dysfunction with damage to vital organs, often with lethal outcome. The aim of the study was to investigate polymorphisms of IL-1β (T-31C), TNF-α (G-308A), IL-10 (G-1082A), IL-17(G-197A), IL-4 (C-589T) genes in COVID-19 patients depending on the outcome of the disease. Methods. We examined 142 patients diagnosed with COVID-19, of whom 122 patients ended the disease with recovery (group 1) and 20 patients died (group 2). Polymorphisms of IL-1β (T-31C), TNF-α (G-308A), IL-10 (G-1082A), IL-17(G-197A), IL-4 (C-589T) genes by genetic method were investigated in COVID-19 patients depending on the outcome of the disease. Results. Analysis of IL-1β (Т-31С), TNF-α (G-308A), IL-10 (G-1082A), IL-17(G-197A), IL-4 (С-589Т) gene polymorphisms in COVID-19 patients showed no statistical differences in recovered patients compared to deceased patients. Statistically significant differences were found in IL-10 gene (genotype -1082A/A). It was found to be recorded 3.8 times more frequently in the group of COVID-19 deceased patients compared to recovered patients (p=0.001; OR=1.027). Conclusion. Among the studied polymorphic variants of IL-1β (T-31C), TNF-α (G-308A), IL-10 (G-1082A), IL-17(G-197A), IL-4 (C-589T) genotype -A/A polymorphism of IL-10(G-1082A) was a significant marker of increased risk of COVID-19 lethal outcome, which can be used as a possible predictor of unfavorable outcome of the disease.

Polymorphisms of genes of interleukin-6 and alpha-1 chain of collagen type 1 in postmenopausal women with knee osteoarthritis

BACKGROUND: To date in the Russian Federation insufficient attention has been paid to the study of IL6 and COL1A1 gene polymorphisms role in the development of knee osteoarthritis. And the results of the single carried out to date studies, devoted to the research of polymorphic variants of the above genes influence on the osteoarthritis development, are insufficient for substantiated conclusions.&#x0D; AIM: To study the frequency of alleles and genotypes of the IL6 gene rs1800795 polymorphism and COL1A1 gene rs1107946 and rs1800012 polymorphisms in postmenopausal women with knee osteoarthritis.&#x0D; MATERIALS AND METHODS: The results of 157 postmenopausal women survey with knee osteoarthritis were selected and analyzed. The control group consisted of 326 women of the same age without signs of joint disease. The study of polymorphisms rs1800795, rs1107946 and rs1800012 was performed by real-time polymerase chain reaction.&#x0D; RESULTS: The conducted studies showed that in the general group of examined women the frequency of all three studied polymorphisms genotypes registration corresponded to the Hardy-Weinberg law. An uneven (p = 0.043) distribution of rs1800795 polymorphism genotypes was found in the group of women with osteoarthritis and in the control group in the study of the IL6 gene polymorphic variants frequency detection. This difference was due to more frequent GG genotype registration of the above polymorphism (odds ratio = 1.75; 95% confidence interval: 1.12–2.72; p = 0.021) among women with knee osteoarthritis. Associations of rs1107946 and rs1800012 COL1A1 gene polymorphisms were not found (p 0.05).&#x0D; CONCLUSIONS: An association between GG genotype of the IL6 gene rs1800795 polymorphism and knee osteoarthritis in postmenopausal women has been established. Genotypes and alleles of COL1A1 gene rs1107946 and rs1800012 polymorphisms were not associated with joint disease.

An Investigation on the Correlation Between Diabetic Foot Infection, Osteomyelitis, Venous Insufficiency, and IL-6 (-174 G&gt;C) and TNF-α (-238 G&gt;A) Gene Polymorphisms

An Investigation on the Correlation Between Diabetic Foot Infection, Osteomyelitis, Venous Insufficiency, and IL-6 (-174 G&gt;C) and TNF-α (-238 G&gt;A) Gene Polymorphisms

Associations between interleukin-13, interleukin-4 and their receptor gene polymorphisms and susceptibility to atopic dermatitis in a Chinese Han population.

Background Atopic dermatitis (AD) is a common skin condition that occurs due to a combined effect of immune dysregulation, skin barrier dysfunction, changes in the cutaneous microbiome, and genetic factors. Recent data from both clinical trials and real-world studies indicate that dupilumab, a biological agent that inhibits interleukin 4 receptor-α is an effective drug in the treatment of AD, which further suggests the important role of IL-13 and IL-4 in the pathogenesis of AD. Objectives To assess the association between gene polymorphisms of IL-13, IL-13 receptor, IL-4, and IL-4 receptor and susceptibility to AD. Methods The single nucleotide polymorphisms (SNPs) of the above-mentioned genes were detected by single base extension (SNaPshot) assay. The association between these SNPs and AD risk was analysed using SPSS software. Results Two hundred and seventy-one subjects including 130 patients with AD and 141 healthy controls were enrolled. There were statistical differences between AD patients and controls in genotype distribution at rs2265753, rs6646259, and rs2254672 of the IL-13 receptor gene (P all < 0.001). Subjects with CG at rs2265753, AG at rs6646259 and TG at rs2254672 had increased risks for AD (P all < 0.001), and subjects with GG at rs2265753, rs6646259, and rs2254672 had reduced risks for AD (P all < 0.001). Limitation This was a single-centre and single-race study, with a relatively small sample size. Conclusions Findings from this study show that rs2265753, rs6646259 and rs2254672 of the IL-13 receptor gene are associated with susceptibility to AD.

Immune gene polymorphisms associated with poor response to platelet transfusion and recombinant factor VII administration in Glanzmann thrombasthenia.

Poor response to platelet and recombinant factor VII administration is a major problem in patients with Glanzmann Thrombasthenia (GT). The risk factors associated with poor response to treatment in these patients are unknown. Some genetic variations of cytokines may contribute to therapy resistance. We evaluated, for the first time, whether genetic polymorphisms on cytokine genes are related to poor treatment response in GT patients. We enrolled 30 patients with GT (15 resistant and 15 non-resistant) and 100 healthy controls. Gene polymorphisms of IL-10 and TNF-α were analysed using TaqMan Realtime PCR, and IL-1, IL-1R1 and IL-1RN were investigated with the RFLP method. In-silico analyses were performed to predict the potential impact of these polymorphisms. In the resistant group, all patients had a variant of the IL-10 gene at the -1082 position (rs1800896), with a GG genotype that was significantly more frequent than the non-resistant group. Analysis between healthy controls and GT patients revealed a probable correlation between rs3783550, rs3783553, rs3917356 and rs2234463 and GT. The In-silico study indicated that TNF-α rs1800629 and IL-10 rs1800896 polymorphisms result in different allelic expressions which may contribute to poor response to therapy. These findings suggest that polymorphisms in the IL-10 and IL-1 receptor antagonist genes may play a role in poor therapy response in GT patients. In addition, some polymorphisms in IL-1α, IL1-β, IL-1R1 and IL-R antagonists might be involved in the GT progression.

Association of Interleukin-12 and Interleukin-18 Polymorphisms with Acute Lymphoblastic Leukemia Disease in Iraqi Patients

Acute lymphoblastic leukemia (ALL) is a blood cancer where high numbers of abnormal, immature lymphocytes called blasts start over-multiplying in the bone marrow. The lymphocyte cells and interleukins are crucial for controlling the immune response in tumor microenvironment. Many of the single nucleotide polymorphisms (SNPs) of some interleukin genes may change protein synthesis or function and regulate the immune response. A lot of these changes have been connected to a high risk of developing cancer. Aim of this study was to investigate the potential association between IL-12 (+1188 A/C) (rs3212227) and IL-18 (–607 A/C) (rs1946518) polymorphism with serum levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) and their genotypes association with the susceptibility to ALL disease in Iraqi patients. The study included 59 ALL patients and 30 healthy controls. The detection of IL-12 and IL-18 SNP genes was determined by ARMS-PCR methods and serum levels of IFN-γ and TNF-α were determined by utilizing enzyme linked immuno-sorbent assay (ELISA) kits. Results observed no significant association of IL-12 and IL-18 polymorphism with serum IFN-γ and TNF-α level. Genotyping frequencies of IL-12 (+1188A/C) CA, AA and CA+AA genotypes showed a strong association with the development of ALL disease, IL-18 genotypes showed no significant association with the disease progression.

Association of IL-4 (− 590 C/T) and IL-6 (− 174 G/C) gene polymorphism in South Indian CKD patients

AimThe present study was undertaken to examine the role of IL-4 (− 590 C/T) (rs2243250) and IL-6 (− 174G/C) (rs1800795) polymorphism and the serum levels of IL-4 and IL-6 in chronic kidney disease (CKD).MethodsThe IL-4 (− 590C/T) and IL-6 (− 174 G/C) polymorphisms were genotyped in 132 CKD patients and 161 controls using PCR–RFLP. Serum IL-4 and IL-6 quantifications were performed by ELISA.ResultsSignificant susceptible associations of CT genotype (OR = 4.56; p < 1.84 × 10–9) and T allele (OR = 1.56; p < 0.010) of IL-4 (− 590C/T) and CC genotype (OR = 2.63; p < 0.032) of IL-6 (− 174G/C) were observed for CKD. The CC genotype (OR = 0.27; p < 9.314 × 10–7) and C allele (OR = 0.63; p < 0.010) of IL-4 (− 590 C/T) revealed strong protective associations. Five-fold increased levels were observed for both IL-6 (p < 0.0001) and IL-4 (p < 0.0043) cytokines in CKD patients than the controls. The IL-4 serum levels (pg/ml) increased significantly in patients with CT and TT genotypes of IL-4 (− 590 C/T) than the controls (6.18 ± 1.80 vs. 3.33 ± 0.48 and 6.14 ± 1.96 vs. 3.21 ± 0.56 respectively). For IL-6 (− 174 G/C) polymorphism, the patients with CC genotype (6.50 ± 1.30 vs. 3.49 ± 1.39) revealed with higher IL-6 serum levels followed by GC genotype (5.00 ± 1.91 vs. 4.01 ± 1.74).ConclusionThe genotypes of IL-4 (590 C/T) and IL-6 (174 G/C) polymorphisms contribute differential susceptibility in south Indian CKD patients. A fivefold increased serum levels of IL-4 (anti-inflammatory) and IL-6 (pro- and anti-inflammatory) cytokines were documented in CKD patients. There observed an opposite trend in disease association for these two cytokines and associated SNPs with CKD in south India.

Association of Cytokine IL-17, IL-4, IL-6, and IL-12 Gene Polymorphisms in Rheumatoid Arthritis Patients in a Tertiary Care Hospital in Bangladesh.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that involves cytokines in its pathogenesis. This study is aimed at investigating if gene polymorphisms in cytokines like IL-17, IL-4, IL-6, and IL-12 affect RA susceptibility and severity in the Bangladeshi population. This was a cross-sectional comparative study that included 40 diagnosed RA patients according to the American College of Rheumatology (ACR) criteria 2010, who were free from other rheumatological diseases, and 40 healthy subjects for comparison. The study used PCR-RFLP to determine the IL-17, IL-4, IL-6, and IL-12 cytokine gene polymorphisms. Patients had a mean age of 37.22 ± 6.70 years. Among the patients, 31 were female and 9 were male. The mean disease duration was 18.11 ± 7.39 months. The study found that rheumatoid arthritis patients with the IL-17F (7488 A/G) polymorphism with GG genotype (P = 0.006, OR = 8.56, 95% CI = 1.77 - 41.33) and IL-12B (1188 A/C) polymorphism with AC (P = 0.012, OR = 3.69, 95% CI = 1.43 - 9.53) and CC (P = 0.013, OR = 7.58, 95% CI = 1.56 - 36.88) genotypes were significantly associated with disease risk. Furthermore, patients with the IL-17F (7488) GG genotype and IL-12B (1188) AC and CC genotypes had higher rheumatoid arthritis disease severity and activity parameters. The study found no significant association between polymorphisms involving IL-4 (590 C/T) and IL-6 (174 G/C) genes and rheumatoid arthritis disease risk in the Bangladeshi population. Gene polymorphisms in cytokines IL-17F (7488 A/G) and IL-12B (1188 A/C) can predict disease susceptibility and severity in Bangladeshi rheumatoid arthritis patients.

Molecular Determination of Tumor Necrosis Factor-alpha, Interleukin-8, Interleukin-10, and C-X-C Chemokine Receptor-2 Genetic Variations and their Association with Disease Susceptibility and Mortality in COVID-19 Patients.

Altered cytokine levels have been associated with poor outcomes among COVID-19 patients. TNF-α, IL-8 and IL-10 are key cytokines in COVID-19 pathogenesis, and CXCR-2 is a major chemokine receptor involved in inflammatory response. Polymorphisms in the genes of these proteins are proposed to influence disease outcomes. In this study, we aimed to find out the association of genetic polymorphisms in TNF-α, IL-8, IL-10 and CXCR-2 genes with susceptibility to and mortality of COVID-19. The present case-control study was conducted on 230 subjects, among whom 115 were clinically diagnosed and RT-PCR-confirmed COVID-19 patients and 115 healthy control subjects. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), CXCR2 +785 C>T (rs2230054) genes were detected by ARMS -PCR assay whereas for IL-10 (-1082 G>A), rs1800896 G>A allele-specific PCR assay was used and their association with COVID-19 susceptibility and mortality was estimated by multivariate analysis. The results were analyzed for risk of infection and mortality through different inheritance models. Frequencies of TNF-α rs1800629 GA, AA, IL-8 rs4073 TA, AA, IL-10 (-1082 G>A), rs1800896 GA and GG, and CXCR2 rs2230054 CT genotypes were significantly higher in COVID-19 patients compared to the control group (p < 0.05). Furthermore, COVID-19 patients had a higher frequency of the polymorphic A allele of TNF-α, the A allele of IL-8, the G allele of IL-10, and the T allele of CXCR2. The risk of susceptibility to COVID-19 was significantly associated with TNF-α rs1800629 GA, GA+AA genotypes and the A allele, IL-8 rs4073 TA, AA genotypes and A allele, IL-10 rs1800872 GA and CC genotypes and C allele, and CXCR2 rs2230054 CT and CT+CC genotypes. TNF-α-GA and AA genotypes and A allele, IL-8 TA and AA genotypes and A allele and CXCR-2 CC and CT genotypes have significant associations with mortality risk in COVID-19 patients, while GA and GG genotypes of the IL-10 are shown to confer significant protection against mortality from COVID-19. The findings of this study provide important insights into the COVID-19 disease and susceptibility risk. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), IL-10 (-1082 G>A), rs1800896 and CXCR2 +785 C>T (rs2230054) are associated with the risk of susceptibility to COVID-19 and with mortality in COVID-19 patients. Further studies with larger sample sizes are necessary to confirm our findings.

Interleukin-6 And Interleukin-10 Polymorphisms In Chronic Lymphoid Leukemia Patients.

A major part of the cytokines secreted from the immune system are interleukins (IL) and their main role is to stimulate the immune system cells. Therefore the genotypic effects of IL-6 and IL-10 on the immune system in CLL were investigated in the study. For this purpose 100 patients diagnosed with CLL and 70 healthy individuals with no cancer history were included in the study. Polymorphisms at IL10 and IL 6 promoter regions (1082 A\G and 819 C\T) and IL6 (174 G\C) polymorphisms were analyzed with RT-PCR. Genotype and allele frequencies were directly calculated. In 100 CLL patients, 45 wild type AA, 40 AG and 15 mutant type GG genotypes were found for the IL 10 1082 A\G region. Genotypic distribution of IL10 819 C\T region was determined as CC, BT and TT genotypes in 37, 50 and 13 patients, respectively. In IL 6 174 G\C region, GG, GC and CC genotypes were determined in 62, 30 and 8 patients, respectively. There is no statistically significant difference between the CLL patients and control groups in terms of IL10 1082 A\G, 819 C\T and IL 6 174 G/C regions (p> 0.05). As a result of the allele frequency calculation of the IL 10 1082 region, the values obtained were A (0.65), G (0.35) for the patient group and (0.61) and G (0.31) for the control group. 819 region allele frequencies were C (0.57) and T (0.33) in the patient group and C (0.48) and T (0.32) in the control group. The IL6 174 region was calculated as G (0.82), C (0.28) in the patient group and G (0.63), C (0.23) in the control group. Given the number of patients within the limits of this study, IL 10 and IL 6 genotype frequencies do not seem to be statistically related to CLL patients. Mutant alleles of all interleukin SNPs were determined at a higher frequency in the patient group as compared to the control group. Therefore, a potential correlation between the SNPs of these interleukins and CLL can be determined in future studies with a higher number of samples.

Association of IL-10–592 C > A /-1082 A > G and the TNFα -308 G > A with susceptibility to COVID-19 and clinical outcomes

BackgroundVariation in host immune responses to SARS-CoV-2 is regulated by multiple genes involved in innate viral response and cytokine storm emergence like IL-10 and TNFa gene polymorphisms. We hypothesize that IL-10; -592 C > A and − 1082 A > G and TNFa-308 G > A are associated with the risk of SARS-COV2 infections and clinical outcome.MethodsGenotyping, laboratory and radiological investigations were done to 110 COVID-19 patients and 110 healthy subjects, in Ismailia, Egypt.ResultsA significant association between the − 592 A allele, A containing genotypes under all models (p < 0.0001), and TNFa A allele with risk to infection was observed but not with the G allele of the − 1082. The − 592 /-1082 CG and the − 592 /-1082/ -308 CGG haplotypes showed higher odds in COVID-19 patients. Severe lung affection was negatively associated with − 592, while positive association was observed with − 1082. Higher D-dimer levels were strongly associated with the − 1082 GG genotype. Survival outcomes were strongly associated with the GA genotype of TNFa. -308 as well as AGG and AAA haplotypes.ConclusionIL-10 and TNFa polymorphisms should be considered for clinical and epidemiological evaluation of COVID-19 patients.

Polymorphisms of CCR5, IL-6, IFN-γ and IL-10 genes in Cuban HIV/AIDS patients

IntroductionGenetic studies have shown associations of several single nucleotide polymorphisms (SNP) with different rates of progression and variation in susceptibility to HIV infection. This study aimed to estimate the frequency of ccr5Δ32, IL-6-174G/C, IFN-γ+874T/A and IL-10-1082A/G polymorphisms in Cuban HIV-infected patients and a group of sero-discordant couples to assess their influence on risk and disease progression. MethodsA cross-sectional study was carried out on 120 subjects registered at the Institute of Tropical Medicine «Pedro Kour» (IPK) and the Ameijeiras Hospital from June 2018 until December 2019. The amplification of fragments of the ccr5, IL-6, IFN-γ and IL-10 genes was performed by polymerase chain reaction followed by identification of polymorphisms using the restriction fragment length polymorphism analysis for IL-6 with the restriction enzymes Nla III. Amplification Refractory Mutation System was used for IFN-γ and IL-10 genes. ResultsThe allelic and genotypic distributions of the genes ccr5, IL-6, IFN-γ and IL-10 did not differ significantly between the two groups. Cell counts and plasma viral load values did not differ significantly between genotypes of the ccr5, IL-6, IFN-γ and IL-10 genes. Only the IL-6 GC genotype was associated with higher viral load values. The combination of alleles of the four considered SNPs showed a highly significant increase in the risk of HIV infection for one of them, but with a very low frequency (<1%). ConclusionThis study contributes to evaluating the frequency of these polymorphisms and their influence on biomarkers of the progression of HIV infection in the Cuban HIV-population.

Circulating IL-6 and not its circulating signaling components sIL-6R and sgp130 demonstrate clinical significance in NSCLC patients treated with immune checkpoint inhibitors.

Introduction: Clinical roles of plasma IL-6 levels have been reported in patients with various cancers, including non-small cell lung cancer (NSCLC), treated with immune checkpoint inhibitors (ICIs). However, the roles of other IL-6 signaling components, soluble IL-6 receptor (sIL-6R) and soluble gp130 (sgp130), in the plasma have not been elucidated. Methods: Blood was collected from 106 patients with NSCLC before initiation of ICI treatment (anti-PD-1 or anti-PD-L1 antibody). Plasma levels of IL-6, sIL-6R, sgp130, and their complexes were assessed by Cox regression hazard model to evaluate their clinical significance. The clinical role of IL-6 or IL-6R genetic polymorphisms was also analyzed. Results: Cox regression analysis showed that higher plasma IL-6 levels significantly predicted unfavorable overall survival (OS; hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.05-1.68, p = 0.012) in NSCLC patients treated with ICIs. However, plasma sIL-6R and sgp130 levels showed no prognostic significance (p = 0.882 and p = 0.934, respectively). In addition, the estimated concentrations of binary IL-6:sIL-6R and ternary IL-6:sIL-6R:sgp130 complexes and their ratios (binary/ternary complex) were not significantly associated with OS (p = 0.647, p = 0.727, and p = 0.273, respectively). Furthermore, the genetic polymorphisms of IL-6 (-634G>C) and IL-6R (48892A>C) showed no clinical role by Kaplan-Meier survival analysis (p = 0.908 and p = 0.639, respectively). Discussion: These findings demonstrated the clinical significance of plasma levels of IL-6, but not of other IL-6 signaling components, sIL-6R and sgp130, suggesting that classical IL-6 signaling, but not trans-signaling, may be related to anti-tumor immune responses in cancer patients treated with ICIs.

The Concentrations of Interleukin-6, Insulin, and Glucagon in the Context of Obesity and Type 2 Diabetes and Single Nucleotide Polymorphisms in IL6 and INS Genes.

Obesity and diabetes are a problem of modern medicine. Although the environmental factors contributing to the development of these diseases are widely known, research into genetic factors is still ongoing. At the same time, the role of inflammation in the pathophysiology of obesity and diabetes is increasingly emphasized. Therefore, the purpose of this study was to investigate the influence of two selected polymorphisms (rs1800795 and rs3842729) on the development of obesity and type 2 diabetes. In this study, 118 participants were examined, including a control group (nonobese and nondiabetic group), an obese group, and a diabetic group. Genotype analysis was performed using the PCR-RFLP method. It has been shown that in patients with the G/G genotype within the rs1800795 polymorphism (IL6), the chance of developing type 2 diabetes is several times lower compared to patients with the G/C and C/C genotypes. However, the rs3842729 polymorphism (INS) does not directly affect the risk of obesity or type 2 diabetes (T2D), although elevated insulin concentrations have been observed in obese and diabetic patients. These results confirm the impact of the rs1800795 polymorphism on the development of diabetes; however, this relationship is more complex and requires further research on other factors.

Prevalence and impact of interleukin-6 and interleukin-10 polymorphisms in Egyptian children with immune thrombocytopenic purpura

Background Recent findings demonstrate that complex immune system dysregulation plays a role in the etiology of immune thrombocytopenic purpura (ITP) Aim Aim The current study aimed to assess the prevalence and impact of interleukin-6 (IL-6) and IL-10 polymorphisms and levels in Egyptian children with ITP. Patients and methods In this case–control study, 25 Egyptian children with newly diagnosed ITP took apart. Their mean age was 9±2.56. They were treated at Tanta University Hospital’s Hematology Unit, Pediatric Department. Furthermore, 25 healthy age-matched and sex-matched children were included as controls. Both groups were subjected to complete blood count, PCR for IL-6 572G&gt;c=rs1800796 and IL-10 627A&gt;C=rs1800872, and enzyme-linked immunosorbent assay measurement of serum levels of IL-6 and IL-10. Results Eight percent of our patients tested positive for IL-6 (572) polymorphism (G/C), 4% tested positive in controls. Meanwhile 4% of cases tested positive for IL-10 (627) polymorphism (A/C), indicating that there was no statistically significant difference between groups. Patients’ levels of IL-6 and IL-10 were considerably higher (P&lt;0.0001). Moreover, there was a statistically significant difference between the acute and chronic cases, with the former having a higher level. The levels of IL-6 and IL-10 and the platelet count showed a statistically significant strong negative correlation. Conclusion IL-10 polymorphisms are thought to play a part in the pathogenesis of childhood ITP. Moreover, IL-6, seems to predict susceptibility to primary ITP in Egyptian children making both promising biomarkers of clinical progression. However, a sizable prospective study is required to find out how cytokine gene polymorphisms affect childhood ITP.