MicroRNA-146a expression as a potential biomarker for rheumatoid arthritis in Egypt

AbstractBackgroundMicroRNAs (miRNAs) are small non-coding RNAs, whose role in regulating diverse immune functions, suggests they might play a role as biomarkers for immune mediated disorders. Studies showed that miRNA-146a (miR-146a) expression is increased by proinflammatory cytokines and is an important modulator of differentiation and function of cells of innate and adaptive immunity.Aim of the workThe current study aimed to evaluate the expression of miR-146a as a potential biomarker for diagnosis of rheumatoid arthritis (RA) and to explore its association with disease activity.Subjects and methodsThe study enrolled 50 Egyptian subjects divided into a patient group, which comprised 25 RA patients, and a control group which comprised 25 healthy individuals. The disease activity for the patients’ group was determined by simplified disease activity index. Relative quantification of miR-146a expression in whole blood was determined using reverse transcriptase quantitative real time polymerase chain reaction.ResultsThere were highly significant statistical differences between patients and healthy controls as regards miR-146a relative expression, erythrocyte sedimentation rate (ESR) and anti-cyclic citrullinated peptide (anti-CCP) (p<0.001). Highly significant statistical differences (p<0.001) were also found between different patients’ subgroups as regards miR-146a relative expression and ESR. miR-146a levels correlated positively with those of ESR, C-reactive protein and anti-CCP (p<0.001).miR-146a illustrated best performance in diagnosing RA, showing the highest sensitivity and specificity (96% and 100%, respectively) (AUC: 0.992 at a cut off value of ⩾2.16) compared to anti-CCP (sensitivity: 68%, specificity: 100% and AUC: 0.87 at a cut off value of ⩾22U/ml) and RF (sensitivity: 56%, specificity: 80% and AUC: 0.992 at a cut off value of ⩾13U/ml).ConclusionThis study demonstrated that miR-146a expression was highly significantly elevated in whole blood of patients with RA. Its diagnostic performance was better than anti-CCP and RF and its level of expression correlates with disease activity

Anti-carbamylated protein antibodies in psoriatic arthritis patients: Relation to disease activity, severity and ultrasonographic scores

Background: Anticarbamylated proteins (anti-CarP) are a novel family of antibodies recently identified in patients with inflammatory arthritis. Aim of the work: To investigate the anti-CarP serum levels in psoriatic arthritis (PsA) patients. The relation of anti-CarP to disease activity and severity as well as to the ultrasonographic findings and scores were well thought-out. Patients and methods: Forty-five PsA patients diagnosed according to the classification of psoriatic arthritis (CASPAR) criteria. 45 matched controls were included. The erythrocyte sedimentation rate (ESR), C-reactive protein and serum anti-CarP antibody were measured. PsA disease activity was recorded according to the modified disease activity score (DAS28). The severity and extent of psoriasis was assessed by the psoriasis area severity index (PASI). Musculoskeletal ultrasound (US) of the small hand joints was performed using grey scale (GS) and power Doppler (PD) to derive composite scores based on abnormal counts and severity. Results: The mean age of the patients was 44.58 ± 6.76 years, 40 females and 5 males (F:M 8:1), disease duration 4.93 ± 3.17 years. Serum levels of anti-CarP antibody were increased in PsA patients (33.48 ± 14.05) compared to controls (12.21 ± 4.71 ng/ml) (p < 0.001). The mean DAS28 was 4.61 ± 1.59 There was a significant correlation between anti-CarP antibody and each of DAS28, ESR, CRP, PASI, the GS and PD joint counts (r = 0.97, r = 0.97, r = 0.97, r = 0.97, r = 0.96, r = 0.9 respectively) as well as with the US joint scores; GSJS and PDJS (r = 0.98, r = 0.97 respectively) denoting severity. Conclusions: Anti-CarP antibody might represent a promising marker to predict joint damage and disease activity in PsA patients

Liver fatty acid binding protein: A potential urinary and tissue biomarker for lupus nephritis

Aim of the work: To assess urinary liver fatty acid binding protein (uL-FABP) levels and tissue expression (tL-FABP) in renal biopsies of active and inactive lupus nephritis (LN) patients and examine their relationship with disease characteristics. Patients and methods: uL-FABP levels and tL-FABP expression were assessed in 75 systemic lupus erythematosus (SLE) patients; 25 active LN, 25 inactive LN and 25 SLE without LN as well as 10 matched healthy control. Results: Mean age was 33.9 ± 6.7 years, disease duration 4.6 ± 2.4 years and were 66 females and 9 males. Patients with active LN had higher uL-FABP higher than patients with inactive LN and without LN. uL-FABP in patients with active and inactive LN significantly correlated with renal SLEDAI (r = 0.96, r = 0.92 respectively and p < 0.0001) and 24-h urinary protein (r = 0.97, r = 0.68 respectively and p < 0.0001) but negatively correlated with the estimated Glomerular Filtration Rate (r = −0.97, r = −0.84 respectively and p < 0.0001). uL-FABP significantly correlated with grade of renal biopsy in active and inactive LN (F = 155.6 and 40.7 respectively, p < 0.0001). L-FABP was highly expressed in renal tissue of LN patients; the tubules seemed to be the main location for tL-FABP staining. The uL-FABP levels significantly correlated with the chronicity index score of renal pathology (F = 17.6, p < 0.0001) and the expression of tL-FABP in active and inactive LN (F = 21.4 and 42.2 respectively, p < 0.0001). Conclusion: Urinary and tissue L-FABP levels were associated with active renal disease. Urinary levels of L-FABP might be a potential non invasive marker for the presence of renal involvement in patients with SLE alternative to renal biopsy

The association of single nucleotide polymorphism of interleukin-21 gene and serum interleukin-21 levels with systemic lupus erythematosus

Background: Systemic lupus erythematosus (SLE) is a common autoimmune disorder which commonly results from the combined effects of a large number of genes. Variations in the DNA sequence in the Interleukin-21 (IL-21) gene may lead to altered IL-21 production and/or activity which can affect an individual’s susceptibility to SLE. IL-21 is a novel class I cytokine produced by activated CD4+ T cells, natural killer T cells and T helper (Th) cells. There is increasing evidence that IL-21 contributes to the pathogenesis of SLE due to its biological activity. Aim of the study: To investigate the association between single nucleotide polymorphism (SNP) of IL-21 rs2221903 gene and serum IL-21 levels with SLE and to detect the possible association between IL-21 serum levels and the pathogenesis of the disease. Subjects and methods: This study was conducted on 30 SLE patients and 20 age and sex matched healthy controls. Serum IL-21 levels were measured using enzyme-linked immunosorbent assay (ELISA) technique and SNP of IL-21 rs2221903 gene was detected by genotyping assay, using real time polymerase chain reaction (RT-PCR). Results: Serum Il-21 levels were significantly higher in patients compared with controls (p < 0.001). Patients with high activity index of SLE had significantly higher levels of serum IL-21 (p value < 0.001). A statistically significant association was found between the T allele of SNP rs2221903 and SLE, whereas; no association between SNP of IL-21 rs2221903 genotypes and SLE or serum IL-21 levels could be detected. Conclusion: IL-21 plays an important role in the immune-pathogenesis of SLE and could be used as a possible target for novel immunotherapy. The T allele of SNP rs2221903 suggests that the IL-21 gene may contribute to an inherited predisposition to SLE