CD226 and CD40 gene polymorphism in Egyptian juvenile idiopathic arthritis children: Relation to disease susceptibility and activity

Aim of the work: To study the association of CD226 rs763361 (C>T) and CD40 rs1883832 (C>T) gene polymorphism with the disease susceptibility and activity in Egyptian juvenile idiopathic arthritis (JIA) children. Patients and methods: 150 JIA children and 194 age and sex matched controls were included. CD226 (C>T) polymorphism was assessed using the tetra amplification refractory mutation system-polymerase chain reaction assay (ARMS-PCR) and restriction fragment length polymorphism (RFLP) for CD40 (C>T). The juvenile arthritis disease activity score (JADAS-27) was used to measure the patients’ disease activity. Results: The mean age of the patients was 11.2 ± 1.7 years, female: male 4:1 and the disease duration was 4.8 ± 2.3 years. 16 were systemic onset, 69 polyarticular and 65 oligoarticular and their mean JADAS-27 was 5.7 ± 5.3. The CD226 TT genotype and T allele were significantly associated with JIA and more frequent than in control (p < 0.001). The CD226 T allele was significantly higher in patients with moderate and high activity compared to mild cases (p = 0.004 and p < 0.001, respectively). The frequency of CD40 C allele was significantly increased in patients with severe and moderate disease activity compared to those with mild (p < 0.001 and p = 0.02 respectively). Conclusion: There was a genetic association between the CD226 and CD40 gene polymorphism and JIA susceptibility with an impact on disease activity in an Egyptian cohort.     

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.     

Th17 cells in Bulgarian children with chronic obstructive lung diseases

Introduction and objectives

Th17 lymphocytes are now widely believed to be critical in various chronic pulmonary diseases. However, there is still a small number of investigations regarding children. We aimed to assess the percentage of Th17 lymphocytes and IL-17A in peripheral blood of children with chronic obstructive lung diseases.

Tumor necrosis factor-α -308 A/G gene polymorphism in children with juvenile idiopathic arthritis: relation to disease activity,damage, and functional status

The study aims to evaluate the clinical significance of serum levels of tumor necrosis factor alpha (TNF-α) and -308 A/G promoter polymorphism in juvenile idiopathic arthritis (JIA) patients and find any association to the subsets, clinical and laboratory features, disease activity, and damage as well as functional disability. Forty-eight JIA children and 30 controls were included in the present study. Juvenile arthritis disease activity score in 27 joints (JADAS-27) was calculated, juvenile arthritis damage index (JADI) was assessed, and Childhood Health Assessment Questionnaire (CHAQ) measured the functional status. Serum TNF-α was assayed by ELISA and gene (-308) promoter polymorphism was determined by polymerase chain reaction. The 48 JIA children (mean age 11.5 ± 2.8 years) were 13 systemic, 17 oligoarticular, and 18 polyarticular onset. The serum TNF-α was significantly higher in patients (90.4 ± 6.3 ng/ml) compared to control (3.5 ± 2.6 ng/ml) (p < 0.0001) with a tendency to be higher in the polyarticular subtype. All controls had TNF-α -308 GG alleles. The frequency of GG genotype tended to be higher in systemic onset compared to oligoarticular and polyarticular subtypes. The serum TNF-α significantly correlated with JADAS-27 (r = 0.32, p = 0.03) and CHAQ (r = 0.37, p = 0.01) and negatively with the presence of GG alleles (r = ?0.48, p = 0.001). The GG alleles were significantly negatively associated with C-reactive protein (r = ?0.32, p = 0.03) with a tendency to negatively correlate with JADAS-27, CHAQ, and JADI-extrarticular (r = ?0.28, p = 0.06; r = ?0.25, p = 0.09 and r = ?0.25, p = 0.09, respectively). There is evidence of a possible influence of the ?308 SNP promoter position on the production of TNF-α, the severity of JIA which may consequently influence the response to anti-TNF-α treatment.     

Relation of anti-annexin V antibodies to disease manifestations and activity in Behҫet’s disease patients

Aim of the work

To assess the role of serum anti-annexin V antibodies in Beh?et’s disease (BD) patients in relation to disease manifestations and activity.Patients and methods65 BD patients and 30 matching controls were included. Disease activity was estimated by the Behçet Disease Current Activity Form (BDCAF). Serum IgG anti-annexin V antibodies titre was measured using the enzyme-linked immunosorbent assay.ResultsThe patients’ age was 36.1 ± 8.5 years and disease duration 7.2 ± 5.2 years; 56 males and 9 females. The serum anti-annexin V antibodies level was significantly increased in the BD patients (50.9 ± 12.9 AU/ml) compared to the control (7.3 ± 3.1 AU/ml) (p < 0.0001). Serum anti-annexin V antibodies were significantly increased in BD patients with ocular involvement, skin lesions and neuro-Behcet’s compared to those without (p = 0.02, p = 0.004 and p = 0.002 respectively). Levels were comparable between those with uveitis, vitrous cells, retinal vasculitis, conjunctivitis and hypopyon and those without (p = 0.12, p = 0.22, p = 0.9, p = 0.67, p = 0.79 and p = 0.46 respectively). While those with xerophthalmia had a significantly higher level of anti-annexin V antibodies (60.6 ± 5.7 AU/ml) compared to those without (50.2 ± 13.1 AU/ml) (p = 0.02). The anti-annexin V antibodies significantly correlated with the BDCAF (r = 0.41, p = 0.001) and age (r = 0.43, p < 0.0001) but not with the disease duration (r = 0.22, p = 0.08), steroid dose (r = ?0.21, p = 0.09) or laboratory investigations. On regression analysis, only the age would predict the anti-annexin V antibodies level (p = 0.02) while the BDCAF would not (p = 0.33).ConclusionThere is a role of apoptosis in the pathogenesis of BD with special relation to the ocular, cutaneous and neurological manifestations and a possible link to the disease activity.     

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.

Is vitamin D level associated with the natural course of atopic dermatitis?

Introduction and objectives

Atopic dermatitis (AD) is a chronic inflammatory disease of the skin. Apart from its well-known role on calcium metabolism, vitamin D is reported to affect skin functions. The study aims were to: compare the vitamin D levels of children with AD and healthy children; investigate the relationship between the severity of AD and vitamin D levels; and investigate the effect of vitamin D on the natural course of AD.

Quality of life in Turkish patients with Familial Mediterranean Fever: Association with fatigue,psychological status,disease severity and other clinical parameters

Aim of the work: To evaluate the quality of life (QoL) in Familial Mediterranean Fever (FMF) patients, and determine its association with fatigue, depression, disease severity and other clinical parameters. Patients and methods: Sixty FMF patients were included. QoL was assessed by Short Form-36 (SF-36), depression by Hamilton Depression Scale (HDS), and fatigue by Fatigue severity scale (FSS). Disease severity score and Mutations of the Mediterranean fever (MEFV) gene were assessed. Results: The mean age of patients was 33.73 ± 9.81 years and disease duration 14.6 ± 12.1 years. They were 35 females and 25 males. FMF patients scored significantly higher in FSS (29.9 ± 17.6) and HDS (15.1 ± 8.5) compared to the control (10.6 ± 7.1 and 6.3 ± 9.4; p < 0.0001 respectively) while all SF36 sub-items except mental health were significantly lower (p < 0.05). MEFV gene mutation was present in 49 (81.7%) patients. The visual analogue scale of pain significantly negatively correlated with the FSS (p < 0.0001), HDS (p < 0.0001) and all SF36 sub-items except mental health (p < 0.0001). Disease duration, age of onset, and duration of attacks showed no significant correlation with FSS, HDS and SF36. Delay in diagnosis significantly correlated with FSS (p < 0.0001) and negatively with SF36 sub-items physical role (p = 0.02), general health (p = 0.01) and social functioning (p = 0.03). Age of diagnosis significantly correlated with FSS (p = 0.03) and negatively with SF36-vitality (p = 0.047). There was a significant effect of disease severity on QoL, fatigue and depression (p < 0.05). Conclusion: QoL is associated with fatigue, depression and disease severity in FMF patients. It should be used in routine clinical evaluation as an outcome measure in FMF.     

Juvenile lupus: Different clinical and serological presentations compared to adult lupus in Egypt

Aim of the work: We aimed to evaluate the differences in clinical presentation, serological pattern and disease activity between juvenile and adult-onset of Egyptian systemic lupus erythematosus (SLE) patients. Patients and methods: 160 Egyptian SLE patients (80 Adult-onset and 80 juveniles) were included. Patients records were reviewed for clinical and laboratory evaluation on presentation. Disease activity at onset was assessed using SLE Disease Activity Index (SLEDAI). Results: The mean age of the adult patients was 29.9 ± 7.2 years and of the juvenile cases (12.8 ± 2.1 years). The female:male ratio of the adults was 10:1 while it was 39:1 in the SLE children. The most common clinical presentation among adult SLE was malar rash (75%) followed by articular manifestations (62.5%), while in juveniles, nephritis (78.8%) followed by articular manifestations (71.2%) were the most common. Juvenile patients had more frequent neuropsychiatric (p = 0.015) and hematologic abnormalities (p < 0.001) at onset; and lupus nephritis (72.5%) compared to adults (36.2%) (p < 0.001) during the first year of presentation. Juvenile SLE showed higher frequency of proteinuria (p < 0.001), hematuria (p = 0.02) and active urinary sediments (p = 0.016). Proliferative nephritis was the most common form among both juveniles and adults. Positivity and titres of both anticardiolipin antibodies and lupus anticoagulant were significantly higher in juvenile SLE. Juvenile SLE patients had significantly higher SLEDAI [median (IQR): 12 (10–22)] compared to adults [median (IQR): 8 (4–12)], p < 0.001. Conclusion: Juvenile SLE patients differ from adult SLE with more frequent major organs affection and significantly higher serological activity. Earlier and more careful assessment with strict management plan and follow-up are needed in juvenile SLE patients.     

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.

Serological markers of inflammatory bowel disease in children from the Western region of Saudi Arabia

Background and study aimsSerological markers including peri-nuclear anti-neutrophil cytoplasmic antibodies (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) have been reported in relation to inflammatory bowel disease (IBD). The aim of this study was to ascertain the prevalence and diagnostic accuracy of pANCA and ASCA antibodies in Saudi children with IBD.Patients and methodsA retrospective case-control study of children with IBD seen at King Abdulaziz University Hospital, Jeddah, between September 2002 and February 2012.ResultsThe study included 131 patients with IBD (86 Crohn’s disease (CD) and 45 ulcerative colitis (UC)) and 67 non-IBD control subjects. Females comprised 51% of CD, 60% of UC and 52% of non-IBD controls. The mean age was 10.7 ± 5.2 years for CD, 8.9 ± 5 years for UC, and 11.2 ± 6.8 years for the non-IBD controls.Positive ASCA-IgA and ASCA-IgG were detected in 35.8% and 35% of CD patients and in 5.8% and 3.7% of the non-IBD controls, respectively. The pANCA was detected in 28.9% of UC patients and in none of the non-IBD controls. The pANCA recognised the myeloperoxidase (MPO) antibody in 36.4% of the patients with UC.No significant difference in the frequency of pANCA between extensive disease and disease limited to the rectosigmoid colon (p = 0.48), and no significant difference in the ASCAs antibodies in patients with or without involvement of the terminal ileum (p = 0.81).ConclusionThe prevalence of ASCA and pANCA antibodies was low in Saudi children with IBD. Therefore, it may not be useful as a screening tool for IBD but it may be employed to aid the diagnosis in clinically suspected cases.     

The neutrophil-to-lymphocyte ratio as a marker of vasculitis activity,severe infection and mortality in anca-associated vasculitis: A retrospective study

IntroductionAnti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a multisystemic disease. Despite the improvement in mortality rate since the introduction of immunosuppression, long-term prognosis is still uncertain not only because of the disease activity but also due to treatment associated adverse effects. The neutrophil-to-lymphocyte ratio (NLR) has been demonstrated as an inflammatory marker in multiple settings. In this study, we aimed to investigate the prognostic ability of the NLR in AAV patients.MethodsWe conducted a retrospective analysis of the clinical records of all adult patients with AVV admitted to the Nephrology and Renal Transplantation Department of Centro Hospitalar Universitário Lisboa Norte from January 2006 to December 2019. NLR was calculated at admission. The outcomes measured were severe infection at 3 months and one-year mortality. The prognostic ability of the NLR was determined using the receiver operating characteristic (ROC) curve. A cut-off value was defined as that with the highest validity. All variables underwent univariate analysis to determine statistically significant factors that may have outcomes. Only variables which significantly differed were used in the multivariate analysis using the logistic regression method.ResultsWe registered 45 cases of AVV. The mean age at diagnosis was 67.5 ± 12.1 years and 23 patients were male. The mean Birmingham Vasculitis Activity Score (BVAS) at presentation was 26.0 ± 10.4. Twenty-nine patients were ANCA-MPO positive, 7 ANCA-PR3 positive and 9 were considered negative ANCA vasculitis. At admission, mean serum creatinine (SCr) was 4.9 ± 2.5 mg/dL, erythrocyte sedimentation rate (ESR) was 76.9 ± 33.8 mm/h, hemoglobin was 9.5 ± 1.7 g/dL, C-reactive protein was 13.2 ± 5.8 mg/dL and NLR was 8.5 ± 6.8. Thirty-five patients were treated with cyclophosphamide, eight patients with rituximab for induction therapy. Twenty patients developed severe infection within the first three months after starting induction immunosuppression. In a multivariate analysis, older age (73.6 ± 10.5 vs. 62.6 ± 11.3, p = 0.002, adjusted OR 1.08 [95% CI 1.01–1.16], p = 0.035) and higher NLR (11.9 ± 7.4 vs. 5.9 ± 5.0, p = 0.002, adjusted OR 1.14 [95% CI 1.01–1.29], p = 0.035) were predictors of severe infection at 3 months. NLR ≥4.04 predicted severe infection at 3 months with a sensitivity of 95% and specificity of 52% and the AUROC curve was 0.0794 (95% CI 0.647–0.900). Nine patients died within the first year. Severe infection at 3 months was independently associated with mortality within the first year (OR 6.19 [95% CI 1.12–34.32], p = 0.037).ConclusionsNLR at diagnosis was an independent predictor of severe infection within the first 3 months after immunosuppression start, and severe infection within the first three months was consequently correlated with one-year mortality. NLR is an easily calculated and low-cost laboratory inflammation biomarker and can prove useful in identifying AAV patients at risk of infection and poorer prognosis.     

Anti-nucleosome antibodies in systemic lupus erythematosus patients: Relation to anti-double stranded deoxyribonucleic acid and disease activity

Aim of the work

To measure the level of anti-nucleosome (anti-NCS) antibodies in systemic lupus erythematosus (SLE) patients and to evaluate their relation with anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibodies and SLE disease activity.

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.

Clinical Significance of Neutrophil/lymphocyte Ratio in Patients With Granulomatosis With Polyangiitis

ObjectiveTo determine to neutrophil-to-lymphocyte ratio (NLR) in granulomatosis with polyangiitis (GPA) patients and to study its relation to disease manifestations and activity.MethodsThe study included 44 GPA patients and 44 matched age and sex controls. Full history taking, thorough clinical examination with more attention to ocular examination, laboratory and radiological investigations were considered. Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS).ResultsThe patients (21 males and 23 females) had a mean age of 45.66 ± 7.24 years, disease duration 6.8 ± 3.6 years and BVAS 50.1 ± 14.3. All patients had a positive cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) while only 5 had a positive p-ANCA. The NLR was significantly increased in the GPA patients (5.1 ± 2.4) compared to the control (1.5 ± 0.8) (P < .0001). Ten patients with uveitis had a significantly higher NLR (6.5 ± 1.9) compared to those without (4.7 ± 2.4) (0.03) while those with proptosis (n = 10), cutaneous manifestations (n = 17) or ischemic heart disease (n = 9) had a significantly lower NLR than those without (P = .0001, P = .017 and P = .046 respectively). The NLR did not significantly correlate with any of the patients’ characteristics. The NLR inversely yet insignificantly correlated with the disease activity (r = -0.02, P = .93).ConclusionThe NLR may have a significant role in the pathogenesis of GPA, the development of uveitis or proptosis, cutaneous manifestations and ischemic heart disease. NLR may serve as a future potential companion to c-ANCA positivity in diagnosing and evaluating GPA and may play a role in the tissue-specific and clinical characteristics.     

A rural environment does not protect against asthma or other allergic diseases amongst Mexican children

Introduction

The commonly held notion that a rural environment decreases the frequency of allergic diseases has proven to be inconsistent amongst children.

Assessment of mitral valve geometric deformity in patients with ischemic heart disease using three-dimensional echocardiography

Background

A full understanding of the geometry of the nonplanar saddle-shaped mitral annulus can provide valuable information regarding the pathophysiology of mitral regurgitation (MR).

Clinical significance of fibromyalgia syndrome in different rheumatic diseases: Relation to disease activity and quality of life

Objective

To describe the frequencies of fibromyalgia syndrome (FMS) in various rheumatic diseases; rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and Behçets disease (BD) patients and to study the relation to clinical manifestations and quality of life (QoL).

Erythrocyte and glomerular C4d deposits as a biomarker for active lupus nephritis

Introduction

Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus (SLE) and histologically evident even in those without clinical manifestations of renal disease.