Relative CTLA-4, PTPN-22, and interleukin 37 mRNA expressions in patients with lupus nephritis.

OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by T-cell immune-dysregulation and loss of tolerance to self-antigens. CTLA-4 and PTPN-22 are involved in the inhibition of T-lymphocytes activation. IL-37 is an anti-inflammatory cytokine that suppresses innate immunity. The relative expression of CTLA-4, IL-37 and PTPN-22 were evaluated as negative regulators of immune response in SLE patients, lupus nephritis (LN) and disease activity. METHODS: Real-Time PCR was performed to determine relative CTLA-4, IL-37, and PTPN-22 mRNA expressions in fifty-eight SLE patients, who were divided into two groups: 29 SLE patients without nephritis and 29 patients with LN, versus fifty controls. RESULTS: There was a significantly high-expression of CTLA-4 and IL-37 genes in SLE patients compared to controls (p=0.005; 0.018 respectively). There was no difference in relative PTPN-22 mRNA expression between the SLE patients and controls. Relative CTLA-4 mRNA expression decreased in LN patients (p=0.044), however, relative IL-37 mRNA over-expressed in LN patients (p=0.001) compared to those without LN. There was a significant over-expression of relative IL-37 andPTPN-22 mRNA in active SLE patients. But, there was a non-significant difference in CTLA-4 expression with disease activity. Regression analysis revealed patients with relative IL-37 mRNA over-expression had two times more to develop lupus nephritis (OR=1.906, 95% CI=1.218-2.983, p=0.005). CONCLUSIONS: Relative IL-37mRNA expression was elevated in SLE patients and associated with renal involvement and disease activity. It could be considered as a new promising predicting tool for LN. Relative PTPN-22 mRNA expression was correlated with disease activity only in SLE patients.

Relative CTLA-4, PTPN-22, and interleukin 37 mRNA expressions in patients with lupus nephritis / Expresiones relativas de ARNm de CTLA-4, PTPN-22 e interleucina 37 en pacientes con nefritis lúpica

Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by T-cell immune-dysregulation and loss of tolerance to self-antigens. CTLA-4 and PTPN-22 are involved in the inhibition of T-lymphocytes activation. IL-37 is an anti-inflammatory cytokine that suppresses innate immunity. The relative expression of CTLA-4, IL-37 and PTPN-22 were evaluated as negative regulators of immune response in SLE patients, lupus nephritis (LN) and disease activity. Methods: Real-Time PCR was performed to determine relative CTLA-4, IL-37, and PTPN-22 mRNA expressions in fifty-eight SLE patients, who were divided into two groups: 29 SLE patients without nephritis and 29 patients with LN, versus fifty controls. Results: There was a significantly high-expression of CTLA-4 and IL-37 genes in SLE patients compared to controls (p=0.005; 0.018 respectively). There was no difference in relative PTPN-22 mRNA expression between the SLE patients and controls. Relative CTLA-4 mRNA expression decreased in LN patients (p=0.044), however, relative IL-37 mRNA over-expressed in LN patients (p=0.001) compared to those without LN. There was a significant over-expression of relative IL-37 andPTPN-22 mRNA in active SLE patients. But, there was a non-significant difference in CTLA-4 expression with disease activity. Regression analysis revealed patients with relative IL-37 mRNA over-expression had two times more to develop lupus nephritis (OR=1.906, 95% CI=1.218–2.983, p=0.005). Conclusions: Relative IL-37mRNA expression was elevated in SLE patients and associated with renal involvement and disease activity. It could be considered as a new promising predicting tool for LN. Relative PTPN-22 mRNA expression was correlated with disease activity only in SLE patients.(AU)

Objetivos: El lupus eritematoso sistémico (LES) es una enfermedad autoinmune caracterizada por la desregulación inmune de las células T, y la pérdida de tolerancia a los antígenos propios. CTLA-4 y PTPN-22 están involucrados en la inhibición de la activación de los linfocitos T. IL-37 es una citocina antiinflamatoria que suprime la inmunidad innata. La expresión relativa de CTLA-4, IL-37 y PTPN-22 se evaluó como reguladores negativos de la respuesta inmune en pacientes con LES, nefritis lúpica (NL) y actividad de la enfermedad. Métodos: Se realizó PCR en tiempo real para determinar las expresiones relativas de ARNm de CTLA-4, IL-37 y PTPN-22 en 58 pacientes con LES, que se dividieron en 2 grupos: 29 pacientes con LES sin nefritis y 29 pacientes con NL frente a 50 controles. Resultados: Hubo una expresión significativamente alta de los genes CTLA-4 e IL-37 en pacientes con LES en comparación con los controles (p=0,005; 0,018, respectivamente). No hubo diferencia en la expresión relativa del ARNm de PTPN-22 entre los pacientes con LES y los controles. La expresión relativa de ARNm de CTLA-4 disminuyó en pacientes con LN (p=0,044); sin embargo, la expresión relativa de ARNm de IL-37 se sobreexpresó en pacientes con LN (p=0,001) en comparación con aquellos sin LN. Hubo una sobreexpresión significativa de ARNm relativo de IL-37 y PTPN-22 en pacientes con LES activo. Pero hubo una diferencia no significativa en la expresión de CTLA-4 con la actividad de la enfermedad. El análisis de regresión reveló que los pacientes con sobreexpresión relativa de ARNm de IL-37 tenían el doble de riesgo de desarrollar nefritis lúpica (OR: 1,906; IC 95%: 1,218-2,983; p=0,005). Conclusiones: La expresión relativa de ARNm de IL-37 fue elevada en pacientes con LES y se asoció con compromiso renal y actividad de la enfermedad. Podría considerarse como una nueva herramienta de predicción prometedora para LN. La expresión relativa del ARNm de PTPN-22 se correlacionó con la actividad de la...(AU)

Preference between serum homocysteine and urinary periostin as early predictive biomarkers of renal dysfunction among uncontrolled diabetics.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) represents a serious public health problem. Environmental toxins, other than infectious agents or exposures can stimulate immune responses which are associated with the occurrence of T2DM. Diabetic nephropathy (DN) is a serious complication of diabetes that leads to changes in the structure and function of the kidneys. The study aimed to detect diagnostic biomarkers for (DN), at an early stage, to prevent disease progression in these patients and improve their outcomes. METHODS: This study was performed on 102 T2DM patients and 80 normal controls. Blood glucose, HbA1c, serum homocysteine (Hcy) and urinary periostin were assessed. Patients were divided into: controlled (n=46) (HbA1c <6.5%) and uncontrolled diabetics (n=56) (HbA1c >6.5%). RESULTS: The study results revealed a significant rise in blood glucose and HbA1c as well as serum Hcy levels in diabetic groups compared to controls. Also, urinary periostin exhibited significant elevation in diabetic groups. Serum glucose, HbA1c and serum Hcy revealed a highly significant difference between diabetic subgroups and control groups, while urinary periostin demonstrated a non-significant difference. Only, urinary periostin showed a significant increase in uncontrolled diabetics. CONCLUSIONS: The highest levels of serum Hcy and urinary periostin were recorded only in the uncontrolled diabetics. Urinary periostin was demonstrated as a more preferable biomarker being a non-invasive sample for predicting renal insult in diabetic subjects. This biomarker could be performed regularly for early detection of DN. Also, it could be added to the periodic medical examinations of workers occupationally exposed to workplace pollutants inducing diabetes.

Cytotoxic T Lymphocyte Antigen 4 Gene +49 A/G (rs231775) Polymorphism and Susceptibility to Systemic Lupus Erythematosus.

AIM: To assess the probable role of +49AG polymorphism in susceptibility to SLE in an Egyptian population. BACKGROUND: Systemic lupus erythematosus (SLE) is a compound inflammatory chronic disease distinguished through the release of autoantibodies. Cytotoxic T lymphocyte associated antigen-4 is a main down controller of T-cell response; its dysregulation could affect SLE pathogenesis by altered T cells activation to self-antigens. OBJECTIVES: To evaluate the CTLA-4 +49AG allelic and genotype frequency in a sample of the Egyptian population and correlate them with disease susceptibility and clinical severity. MATERIALS AND METHODS: Including 100 patients with SLE and 100 healthy controls (age and gender matched), CTLA-4 exon 1 49 A>G Genotyping was done using Real-Time PCR. RESULTS: No difference was noticed in genotype or allele distributions of the studied polymorphism between both groups. Similar genotypes and allele frequencies were established for the 2 groups after their stratification by the age of disease onset, clinical course, or severity. CONCLUSION: CTLA-4 +49AG gene polymorphism is not linked with the liability to develop SLE in the studied Egyptian population. Yet it is significantly related to disease severity.

Inducible clindamycin resistance in clinical isolates of staphylococcus aureus in Suez Canal University Hospital, Ismailia, Egypt.

INTRODUCTION: The increasing incidence of methicillin resistance among Staphylococci has led to renewed interest in the usage of macrolide-lincosamide-streptogramin B (MLSB) antibiotics to treat S. aureus infections, with clindamycin being the preferable agent owing to its excellent pharmacokinetic properties. Inducible clindamycin resistance my lead to therapeutic failure. AIM: Detection of the prevalence of constitutive and inducible clindamycin resistance in clinical isolates of S. aureus to improve the clinical outcomes in patients. METHODOLOGY: A total of 176 non-duplicate staphylococcal isolates were isolated from different clinical samples. Methicillin resistance was detected using Cefoxitin disk diffusion (CDD) method. Phenotypic clindamycin resistance was performed for all isolates by D test. Polymerase Chain Reaction (PCR) assay were done for detection of erm resistance genes (ermA, ermB and ermC). RESULTS: Out of 176 strains of S. aureus, 108 isolates (61.3%) were identified as MRSA. Erythromycin and clindamycin resistance was detected in 96 isolates (54.5%) and 68 isolates (38.6%) respectively. Clindamycin resistance (cMLSB) was significantly higher (p value < 0.001) in MRSA strains (56 isolates) compared to MSSA (12 isolates). Resistant genes were detected in 160 isolates (91%). The ermA gene was detected in 28 isolates (16%), the ermB gene was detected in 80 isolates (45.5%) (p < 0.001). CONCLUSIONS AND RECOMMENDATIONS: The frequency of constitutive and inducible clindamycin resistance in MRSA isolates emphasizes the need to use D test in routine antimicrobial susceptibility testing to detect the susceptibility to clindamycin as the inducible resistance phenotype can inhibit the action of clindamycin and affect the treatment efficacy.

Association of autoimmune regulator gene polymorphism with susceptibility to rheumatoid arthritis in Egyptian population.

The autoimmune regulator (AIRE) gene controls autoimmunity via its transcript AIRE protein that suppresses naïve T cells during central selection. The role of AIRE polymorphism in rheumatoid arthritis (RA) autoimmunity remains elusive. This study aimed to investigate the association of two selected SNPs, namely, rs760426 and rs2075876, with RA susceptibility in the Suez Canal Zone population. The study population included 100 RA patients, and the control group included 100 healthy subjects who were age- and sex-matched to the RA group. SNP genotyping was performed using real-time polymerase chain reaction-based allelic discrimination assay, the odds ratio was defined to assess the strength of the association. For rs760426, combining genotypes data revealed a significant increase for A/G genotype in the RA cases (47%, n = 47) than in the control group (27%, n = 27) in both co-dominant and over-dominant models (P = 0.013 and 0.003 respectively). In addition, rs760426 correlated to duration of RA (P = 0.031) and anti-cyclic citrullinated peptide antibody (P = 0.021). For rs2075876, there was a significant increase in the A/A genotype in RA patients compared with control subjects. In the co-dominant model, the frequency of A/A was 14% and 7% respectively (P = 0.02). In contrast to rs760426, rs2075876 associated with the risk of increased body mass index (P = 0.014) and the positivity of rheumatoid factor (RF) (P = 0.043). The frequency of minor alleles, G allele in rs760426 SNP, and A allele in rs2075876 was higher in RA patients than in control. The haplotype frequency of both G and A alleles in rs760426 and rs2075876 receptively was 11% in RA group with statistically significant difference (P = <0.001) between RA patients and healthy control. SNPs rs760426 and rs2075876 in the AIRE gene may contribute to the risk for RA susceptibility. These two polymorphisms were associated with variable risk factors and predictive biomarkers for RA. The mutant allele (G) of rs760426 SNP has significant indication of poor prognosis.

Genotoxic Effects Due to Exposure to Chromium and Nickel Among Electroplating Workers.

Using chromium and nickel for electroplating is important in many industries. This process induces variable adverse health effects among exposed workers. The aim of this study is to detect the genotoxic effects of combined exposure to chromium and nickel among electroplating workers. This study was conducted on 41 male workers occupationally exposed to chromium and nickel in the electroplating section of a factory compared to 41 male nonexposed individuals, where full history and clinical examination were performed. Laboratory investigations included measurement of serum chromium, nickel, 8-hydroxydeoxyguanosine (8-OHdG), and micronuclei were measured in buccal cells. In exposed workers, serum chromium ranged from 0.09 to 7.20 µg/L, serum nickel ranged from 1.20 to 28.00 µg/L, serum 8-OHdG ranged from 1.09 to12.60 ng/mL, and these results were statistically significantly increased compared to nonexposed group ( P < 0.001). Electroplaters showed higher frequencies of micronuclei in buccal cells when compared to nonexposed (ranged from 20.00 to 130.00 N/1,000 versus 2.00 to 28.00 N/1,000; P < 0.001). Linear regression models were done to detect independent predictors of 8-OHdG and micronucleus test by comparing exposed and nonexposed groups. The model found that exposure to chromium and nickel increases serum 8-OHdG by 4.754 (95% confidence interval [CI]: 3.54-5.96). The model found that exposure to chromium and nickel increases micronucleus by 35.927 (95% CI: 28.517-43.337). Serum 8-OHdG and micronucleus test in buccal cells were increased with combined exposure to chromium and nickel. The current research concluded that workers exposed to nickel and chromium in electroplating industry are at risk of significant cytogenetic damage.