Elevated tissue transglutaminase antibodies in juvenile idiopathic arthritis children: Relation to neutrophil-to-lymphocyte ratio and disease activity

Background: Subclinical gut inflammation is described in juvenile idiopathic arthritis (JIA), so has joint involvement been related to celiac disease (CD). The well-known involvement of tissue transglutaminase (tTG) in the pathogenesis of CD stimulated progress in the field of autoimmune diseases. Aim of the work: To screen JIA children for tTG antibodies and to detect its relation to the neutrophil-lymphocyte ratio (NLR) and disease activity. Patients and methods: The study included 44 JIA children with 44 matched controls. All subjects had no GIT symptoms suggestive of CD. Disease activity was assessed using the juvenile arthritis disease activity score in 27 joints (JADAS-27). The tTG antibodies (IgA and IgG) were assessed. Results: The patients mean age was 12.5 ± 2.8 years and disease duration 5.01 ± 2.9 years; Female:Male 3.4:1. The mean JADAS-27 score was 12.6 ± 2.04. tTG antibodies were positive in 43.2% of the patients compared to 18.2% control (p = 0.01). Antibodies positivity was comparable according to gender and subtypes. The NLR in JIA children (1.62 ± 0.58) was significantly higher than in control (1.3 ± 0.5) (p = 0.006). Those with positive tTG antibodies had a significantly reduced body mass index (p = 0.02) and increased NLR (p = 0.02) compared to those with negative tTG. Only NLR and JADAS-27 would significantly predict antibodies positivity (p = 0.037 and p = 0.04, respectively). Conclusion: Increased tTG antibodies are frequent in JIA children raising the possibility of an associated subclinical CD. Markedly reduced BMI and increased NLR could forecast the presence of these antibodies. In addition to the JADAS-27, the NLR is a simple test that could predict this association and could be a useful biomarker.     

Serum BLyS and APRIL as possible indicators of disease activity in pediatric systemic lupus erythematosus and juvenile idiopathic arthritis

Aim of the workTo assess serum levels of B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) to determine their correlations with disease activity in pediatric systemic lupus erythematosus (pSLE) and juvenile idiopathic arthritis (JIA) patients.Patients and methodsTwenty-nine pSLE patients and 33 JIA patients were recruited. SLE disease activity was assessed using the systemic lupus erythematosus disease activity index (SLEDAI), while the juvenile arthritis 27 joint disease activity score (JADAS-27) was calculated for JIA patients. Serum samples were assayed for BLyS and APRIL by the enzyme linked immunosorbent assay (ELISA).ResultsSerum BLyS and APRIL were elevated in both pSLE and JIA patients compared to controls. Serum BLyS levels correlated with both SLE and JIA disease activity (p = 0.042, p = 0.019, respectively) whereas serum APRIL levels correlated positively with JADAS-27 and inversely with SLEDAI (p = 0.001, p = 0.02, respectively). Elevated serum BLyS and APRIL were significantly associated with a lower incidence of nephritis (p = 0.043, p = 0.016, respectively), while elevated serum APRIL significantly associated with negative anti-dsDNA in pSLE patients (p = 0.017). In JIA patients, both serum BLyS and APRIL were significantly associated with the presence of ANA (p = 0.008, p < 0.001, respectively), while high serum APRIL associated with the presence of RF (p = 0.035). APRIL and BLYS levels correlated with each other positively in JIA but inversely in pSLE patients.ConclusionSerum BLyS showed elevated levels that correlated significantly with pSLE and JIA disease activity, accordingly anti-BLyS therapy might be of great benefit to offset disease flare. The inverse correlations observed between APRIL with both BLyS and disease activity in pSLE patients raises the possibility of being a down regulator of the disease process.     

Role of glutathione S-transferases polymorphisms and monocyte CD64 expression in Egyptian patients with systemic lupus erythematosus

Aim of work

To study the genetic variants of glutathione S-transferases and monocyte CD64 expression in systemic lupus erythematosus patients and to evaluate their role in disease susceptibility, activity and damage.

Role of MyD88-adaptor-like gene polymorphism rs8177374 in modulation of malaria severity in the Pakistani population

Introduction

The present study was designed to investigate the association between rs8177374 polymorphism and malaria symptoms due to exposure of Plasmodium vivax and Plasmodium falciparum.

RS 10767664 gene variant in Brain Derived Neurotrophic Factor (BDNF) affect metabolic changes and insulin resistance after a standard hypocaloric diet

Background

Role of BDNF variants on change in body weight and cardiovascular risk factors after weight loss remains unclear in obese patients.

Antiretroviral therapy immunologic non-response in a Brazilian population: association study using pharmaco- and immunogenetic markers

Background

Antiretroviral therapy (ART) saved millions from HIV-1 infection and AIDS, but some patients do not experience adequate CD4+ T cells gain despite achieving viral suppression. The genetic component of this condition is not yet completely elucidated.

CXCR4 (CD184) expression on stem cell harvest and CD34+ cells post-transplant

Objectives/backgroundCXCR4 is a receptor for stromal-derived factor-1 (SDF-1), a molecule that has a chemotactic activity for lymphocytes and is important in homing of hematopoietic stem cells to their adult marrow. We evaluated the CXCR4 (CD184) expression in the harvest cells and in the post-transplant bone marrow (BM) and its relation to engraftment, as determined by the consensus criteria and chimerism.MethodsThis is a prospective study which included 30 patients undergoing hematopoietic stem cell transplantation; 15 patients received autograft and 15 patients received allograft on dates between January 2012 and May 2014. We assessed CD184 (CXCR4) using flow cytometry in the harvest cells together with post-transplant BM assessment on Day 28 and Day 90 for complete morphologic, molecular studies, and detection of CD184 expression on CD34⁺ cells with chimerism studies on total peripheral blood mononuclear cells.ResultsDiagnoses of the enrolled patients were as follows: seven (24.1%) with acute myeloid leukemia, eight (27.6%) with multiple myeloma, four (13.8%) with acute lymphoblastic leukemia, three (10.3%) with non-Hodgkin lymphoma, two (6.9%) with myelodysplastic syndromes, two (6.9%) with aplastic anemia, two (6.9%) with chronic myeloid leukemia, one (3.4%) with Hodgkin lymphoma, and one (3.4%) with plasmacytomas. One patient died and was excluded from the study because there were not enough data about engraftment. There was no statistical significance between the level of CD184 in stem cell harvest and the prediction of successful engraftment (p > 0.05) as well as in Day 28 BM sample (p > 0.05), whereas there was a statistical significance between the level of CD184 in Day 90 BM sample and the occurrence of successful engraftment (p = 0.002).ConclusionSDF-1/CXCR4 axis plays a crucial role in engraftment; however, more studies are warranted to assess their expression post-transplant. Evaluating the ligand (chemokine, SDF-1) or its receptor (CXCR4) may serve as potential surrogate markers for assessment of engraftment.     

Methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in rheumatoid arthritis patients: Correlation with serum osteopontin levels and disease activity

BackgroundRheumatoid arthritis (RA) is a systemic, chronic inflammatory disease with genetic predisposition. Osteopontin (OPN) is overexpressed in RA and plays a key role in the perpetuation of synovitis. Not all RA patients show the same level of response to methotrexate (MTX) suggesting genetic variations in the drug-metabolizing enzymes.Aim of the workTo detect methylene-tetra-hydrofolate reductase (MTHFR) 677C/T and 1298A/C gene polymorphisms in RA patients treated with MTX and to investigate the relationship with serum OPN levels and disease activity.Patients and methods62 RA patients and 21 healthy controls were included. Serum OPN was measured using ELISA. Genotyping of MTHFR gene was carried out by polymerase chain reaction-restriction fragment length polymorphism. Disease activity score in 28 joints (DAS28) and the modified health assessment questionnaire (MHAQ) were assessed.ResultsThe patients’ age was 42.7 ± 12.7 years, F:M (4.6:1) and a disease duration of 5.7 ± 4.6 years. Their DAS28 was 4.1 ± 1.6 and the MHAQ (median 1; range 0–2.3). Serum OPN levels in RA patients (median 8.8; range 4–44.5 ng/ml) were significantly higher than in control (5.6; 2.1–10.9) (p = 0.002). In RA patients, serum OPN significantly correlated with the duration of morning stiffness (p = 0.009), ESR (p < 0.0001) and DAS28 (p < 0.0001). MTHFR (677C>T) polymorphisms significantly correlated with MHAQ (p = 0.012) while (1298A>C) polymorphisms significantly correlated with tender joint count (p = 0.04). OPN levels were higher among patients with MTHFR (1298A/C) AC genotype (8.9; 4.1–33.9 ng/ml), while in those with (677C>T) polymorphisms it was higher among those with CT genotype (8.9; 4.1–44.5).ConclusionSerum OPN level relates with the degree of rheumatoid activity.     

Study of CD4+, CD8+, and natural killer cells (CD16+, CD56+) in children with immune thrombocytopenic purpura

Objective/backgroundTo assess the percentage of CD4⁺, CD8⁺, and natural killer cells (CD16⁺, CD56⁺) in children with immune thrombocytopenic purpura (ITP) at presentation and study their impact on disease chronicity.MethodsThis case–control study was conducted at the Pediatric Hematology and Oncology Unit, Menoufia University Hospital (tertiary care center in Egypt). The study was held on 30 children presenting with ITP; they were followed-up and classified into two groups: 15 children with acute ITP; and 15 children with chronic ITP. Patients were compared to a group of 15 healthy children of matched age and sex. Measurements of CD4⁺, CD8⁺, and natural killer cells (CD16⁺, CD56⁺) by flow cytometry were assessed and compared in these groups.ResultsCD4⁺ and CD4⁺/CD8⁺ were significantly lower in acute and chronic patients than the control group (p < 0.05 and p < 0.001, respectively), with no significant difference between acute and chronic patients (p > 0.05). However, CD8⁺ was significantly higher in acute and chronic patients than the control group (p < 0.05), with no significant difference between acute and chronic patients (p > 0.05). Natural killer cell percent was significantly lower in acute patients than the control group (p < 0.001), with no significant difference between chronic and control groups (p > 0.05).ConclusionITP is associated with immunity dysfunction denoted by the increase in cytotoxic T lymphocytes and the decrease in natural killer cells.     

Correlation of OX40 ligand on B cells with serum total IgE and IL-4 levels by CD4+ T cells in allergic rhinitis

Introduction and objectives

Allergic rhinitis (AR) is a classic Th2-mediated disease, with important contributions to the pathology of interleukins 4, 5, and 13. The co-stimulatory molecule of OX40 and its ligand interaction participate in the immune response by regulation of Th1/Th2 cells balance. Considering the paucity of information on the relation between OX40 ligand (OX40L) and AR, this study aimed to examine its expression on B lymphocytes.

Metabolic syndrome in HIV-infected middle-aged women on antiretroviral therapy: prevalence and associated factors

Objectives

To determine the prevalence of metabolic syndrome (MetS) and its associated factors in a group of HIV-infected middle-aged women.

Association of endothelial lipase Thr111Ile polymorphism with proliferative retinopathy in type 2 diabetes patients

AimOur previous study demonstrated that the endothelial lipase (EL) C.584C>T polymorphism (rs2000813, p.Thr111Ile) was significantly associated with diabetic retinopathy (DR). The present work was conducted to see if this specific variant of the EL gene was more specifically linked to the severity of DR.MethodsThis retrospective cohort study was based on a review of the institutional charts of 287 type 2 diabetes patients (mean age = 59.7 years; mean BMI = 29.0 kg/m²; mean HbA_1c = 8.4%) genotyped for the EL C.584C>T polymorphism (rs2000813, p.Thr111Ile). The stage of DR was also determined for each genotype (CC, CT, TT).ResultsOn univariate analysis, the minor allele homozygote TT variant was significantly associated with severe DR (OR: 4.3; 95% CI: 1.4, 13.1) compared with the major CC homozygote. No significant result was found for the CT heterozygote. Multivariate analysis revealed an increased risk for TT homozygotes to present with severe non-proliferative DR (OR: 8.09; 95% CI: 1.23, 53.1) or proliferative DR. Other associations were not significant.ConclusionMinor allele homozygosity for this EL variant (c.584C>T) could be a significant risk factor for developing severe, sight-threatening disease due to proliferative DR. Further prospective studies of this EL polymorphism in a larger population sample are needed to confirm these results.     

Clinical significance of vitamin D deficiency and receptor gene polymorphism in systemic lupus erythematosus patients

Introduction

The vitamin D receptor (VDR) gene is a candidate for susceptibility to autoimmune disorders.

CD14++CD16+ monocyte subset expansion in rheumatoid arthritis patients: Relation to disease activity and interleukin-17

Aim of the workMonocytes are divided into three major subsets based on the expression of the cluster of differentiation CD14 and CD16. The aim of this work was to determine which of the CD16⁺ monocyte subpopulations is expanded in rheumatoid arthritis (RA) and its association with disease activity and interleukin-17 (IL17) levels.Patients and methodsFifty-three RA patients and 20 controls were enrolled in this study. Flow cytometry was performed to detect monocyte subsets and IL17 was measured by ELISA. Disease activity score (DAS28) was assessed.ResultsCD14⁺⁺CD16⁺ monocyte percentage was significantly higher in long standing RA patients compared with early patients and controls (p < 0.01, p < 0.001 respectively). It was significantly higher in patients with RA disease activity and remission compared with the controls (p < 0.001, p < 0.01 respectively). It was not significantly associated with resistance to disease modifying antirheumatic drugs (DMARDs), C-reactive protein, rheumatoid factor and anti-CCP positivity (p > 0.05). It significantly correlated with IL17 (p < 0.002). CD14⁺CD16⁺ monocyte percentage was not significantly correlated with any of the above parameters. IL17 level was significantly higher in patients with early and long standing RA compared to controls (p < 0.01, p < 0.001 respectively). IL17 was higher in RA patients with active disease compared to those in remission and controls (p < 0.01, p < 0.001 respectively). It was higher in RA patients resistant to DMARDs than in responding patients (p < 0.017).ConclusionCD14⁺⁺CD16⁺ monocyte subpopulation was expanded in long standing RA and was correlated with IL17 levels indicating its potential pathogenic importance in RA and may represent an attractive target for future therapeutic interventions.     

Single nucleotide polymorphisms of the genes encoding IL-10 and TGF-β1 in Iranian children with atopic dermatitis

Background

Atopic dermatitis is an inflammatory skin disease in which both genetic and environmental factors interact to determine the susceptibility and severity of the disease.

CD14 and IL6 polymorphisms are associated with a pro-atherogenic profile in young adults with acute myocardial infarction

This study investigated the relationship of polymorphisms in genes encoding CD14, IL-6 and TLR4 with metabolic, inflammatory and endothelial markers in young adults with acute myocardial infarction (AMI). Glucose, lipids, nitrate and inflammatory markers, flow mediated vasodilatation (FMV) and flow mediated by nitrate (FMN) were evaluated in 102 AMI and 108 non-AMI (control group) young individuals (<45 years). CD14 ?260C>T (rs2569190), IL6 ?174G>C (rs1800795) and TLR4 c.896A>G (rs4986790) and TLR4 c.1196C>T (rs4986791) polymorphisms were analyzed by PCR–RFLP. Minor allele frequencies of CD14, IL6 and TLR4 polymorphisms were similar between AMI and control groups (p > 0.05). In AMI group, individuals carrying IL6 ?174CC genotype had higher serum triglycerides, VLDL cholesterol and glucose compared to the IL6 ?174GG/GC genotype carriers (p < 0.05). Multiple logistic analysis showed that IL6 ?174CC genotype carriers had increased risk for hyperglycemia (>5.77 mmol/l) [OR: 6.75, 95 % CI: 1.80–24.40, p = 0.004] and hypertriglyceridemia (>2.68 mmol/l) [OR: 3.00, 95 % CI: 1.00–9.00, p = 0.043]. Moreover, CD14 ?260TT genotype was associated with reduced serum HDL cholesterol [OR: 3.10, 95 % CI: 1.00–9.01, p = 0.044] and apolipoprotein AI [OR: 3.20, 95 % CI: 1.00–9.70, p = 0.038] in AMI group. Relationship between CD14 and IL6 variants and altered inflammatory and endothelial (nitrate, FMV and FMN) markers was not found in both AMI and control groups. The IL6 ?174G>C and CD14 ?260C>T polymorphisms are likely to be associated with a pro-atherogenic profile but not with increased inflammatory markers and endothelial dysfunction in young AMI patients.     

Urological comorbidities in Egyptian rheumatoid arthritis patients: Risk factors and relation to disease activity and functional status

Aim of the work: To assess the urological disorders in rheumatoid arthritis (RA) patients, analyse the risk factors and to find their relation to disease activity and functional status. Patients and methods: 291 RA patients (253 females and 38 males; F:M 6.7:1) and 242 matched controls were included. Urological disorders in the form of urinary tract infections (UTI), urolithiasis and acute urine retention (AUR) were assessed, risk factors were analysed. Disease activity score (DAS-28) and modified health assessment questionnaire (mHAQ) were calculated. Results: RA patients had more frequent urological disorders (38.14%) than controls (20.66%), more UTI (p < 0.001) and this difference persisted in females (p < 0.001). Urolithiasis tended to be more frequent in RA patients (p = 0.3); the difference was significant between the female patients and controls (p = 0.04). Urinary stones were comparable between the male patients and controls (p = 0.2). RA patients had more AUR (4.8%) than the controls (2.1%) (p = 0.07). Asthmatic patients particularly the females had more UTI (p = 0.001 and p < 0.001 respectively). UTIs were observed with higher steroid doses (p = 0.04) and urolithiasis were noticed more in hypertensive female patients (p = 0.03). Patients with higher DAS-28 and mHAQ developed more urological comorbidities (p0.49 and p = 0.82 respectively). UTI and urolithiasis were detected in patients with higher DAS 28 (p = 0.1 and p = 0.4 respectively). Conclusion: RA patients were found to have more urological disorders. Bronchial asthma, hypertension and higher steroid doses may increase risk for urinary comorbidities in RA. Patients with higher DAS28 and mHAQ had more urological comorbidities, however without statistically significant difference.     

Association of neutrophil to lymphocyte ratio with disease activity indices and musculoskeletal ultrasound findings in recent onset rheumatoid arthritis patients

Aim of the work

To study the relation between neutrophil-lymphocyte ratio (NLR) with disease activity indices and with musculoskeletal ultrasonographic findings in recent onset rheumatoid arthritis (RA) patients.

Polymorphism in the IL10 promoter region and early markers of atherosclerosis: The Cardiovascular Risk in Young Finns Study

ObjectiveInflammatory factors modify the risk of coronary heart disease. Pleiotropic cytokine interleukin-10 (IL-10) has been suggested as modifying risk for atherosclerosis. Promoter region genetic polymorphism of IL-10 gene (IL10) is known to be associated with the variation of IL-10 production. We investigated whether single-base exchange polymorphisms ?1082 G>A (rs1800896), ?819 C>T (rs1800871) and ?592 C>A (rs1800872) at IL10 gene are associated with risk factors and early markers of atherosclerosis in young subjects.Methods and results: As a part of the Cardiovascular Risk in Young Finns Study, we determined carotid artery compliance (CAC), stiffness index (SI) and Young's elastic modulus (YEM), intima media thickness (IMT), IL10 genotype and atherosclerosis risk parameters for 2260 subjects aged 24–39 years. In male subjects CAC was lower in carriers of IL-10 high- to intermediate-producer haplotype ?1082 G; ?819 C; ?592 C (GCC+, 1.96 ± 0.67) than in noncarriers (GCC?, 2.10 ± 0.62, %/10 mmHg, mean ± SD, p = 0.0010). An inverse association was observed in SI (GCC+, 5.76 ± 2.12 and GCC?, 5.26 ± 1.46, p = 0.0034) and YEM (GCC+, 347 ± 165 and GCC?, 305 ± 110, mm Hg · mm, p = 0.0005). Associations remained significant when adjusted to age, BMI, smoking and serum lipids as well as fasting glucose and insulin levels. The genetic effect size for these parameters was not significant in women.Conclusions: IL10 promoter region high- to intermediate-producer haplotype GCC associates with decreased arterial elasticity in men. These results are in disconcordance with the supposed antiatheromatous properties of IL-10.