MIR-146A and TLR4 gene expression in predicting rheumatoid arthritis disease

Disease Activity Score 28 (DAS28) isthe most widely used method for rheumatoid arthritis(RA) disease activity evaluation. However, it may not reflect disease activity accurately being a subjective tool dependent on patient's self-health assessment and evaluation of swollen and tender joint counts. Therefore, finding a suitable blood genetic marker for accurate monitoring of RA disease activity has become essential. Therefore, the aim of this study was to assess miR- 146a and TLR4 expression in PBMCs of RA patients and to study their value as potential molecular biomarkers for RA disease activity in comparison to DAS28 score. This study was conducted on 51 RA patients and 15 age and sex matched healthy subjects as control group. The relative gene expression levels of miR-146a and TLR4 were determined by reverse transcriptase quantitative real time polymerase chain reaction. There were statistically significant differences between patients and healthy controls as regards miR-146a and TLR4 expression. In addition, statistically significant differences were observed between different patients’ subgroups as regards miR-146a and TLR4 expression. Moreover, miR-146a and TLR4 expression levels showed significant positive correlationswith those of morning stiffness durations, tender joints counts, swollen joints counts, visual analogue scale values, erythrocyte sedimentation rates, CRP, Anti- CCP antibody and DAS28.MiR-146aillustrated the best performance characteristics particularly in differentiating between high and moderate disease activity grades, showing highest sensitivity and specificity.Furthermore, there was a statistically significant increase in the expression levels of miR-146a and TLR4 in PBMCs of RA patients with ankles and/or feet joints involvement, as compared with those without involvement.Conclusion: MiR-146a and TLR4 were overexpressed in PBMCs of RA patients and were correlated with disease activity and radiographic progression especially miR-146a.Keywords: DAS28, Larsen score, RA, reverse transcriptase quantitative real time PCR

Validity of Doppler subclinical synovitis as an activity marker associated with bone erosions in rheumatoid arthritis patients during clinical remission

Introduction: Clinical remission is a realistic goal in rheumatoid arthritis (RA) patients. Doppler signals-synovitis may also be considered predictive of clinical flare-ups in RA. Objective: The aim of this study was to detect subclinical synovitis and erosions by musculoskeletal ultrasound (MSUS) in RA patients with clinical remission and free from physical synovitis. Materials and methods: 41 RA patients were studied who achieved clinical remission for at least 6 months proved by clinical disease activity index (CDAI) and DAS28 without tender neither swollen joints. MSUS of 22 joint done for each patient, the data of gray scale (GSUS) and color Doppler ultrasound (CDUS) graded on a semi-quantitative scale from 0 to 3. Results: The percentage of RA patients with subclinical synovitis present in at least one joint with CDUS ⩾ 1, and CDUS ⩾ 2 were 70.7% and 29.2% respectively. The results of CDUS were significantly lower with biologic agents compared to patients on conventional disease modifying anti-rheumatic drugs (DMARDs) alone (p = 0.01). There was a strong association between CDUS synovitis and MSUS bone erosions (p < 0.00001). Conclusion: Doppler detected subclinical synovitis could be considered a reliable marker to appraise disease activity in RA patients compared to DAS28 and CDAI, in associated joint destruction secondary to erosions

Serum IL17 and IL4R RS1805010 genotypes: relationship with rheumatoid arthritis disease activity in Egyptian patients

Rheumatoid arthritis(RA) is characterized by the presence of a relative state of imbalance between pro- and anti-inflammatory cytokines such as Interleukin(IL)17 and IL4, respectively. IL4 is supposed to regulate production of IL17 from T-helper (Th)17 cells. However, this regulatory function might be affected by singlenucleotide polymorphism (SNP) of IL4 receptor (IL4R) gene, rs1805010. The current study aimed to assess serum IL17 level in Egyptian patients with RA according toIL4Rrs1805010 genotypes,and to detect possibleassociations betweenIL17/ IL4R genotypesand clinical status, disease activity as well as effect of treatment. Serum IL17 was assessed by ELISA, and qPCR was used to determine the genotypes of IL4R SNP rs1805010. Serum IL17 was significantly increased in patients’ samples as compared to controls. According to IL4R genotypes, patients with AG and GG genotypes showed significantly higher IL17 levels than control subjects with corresponding genotypes. Within RA group, significantly higher IL17 were found in GG carriers compared to those with AA genotype. The G allele was significantly associated with higherythrocyte sedimentation rate(ESR), increased disease activity score in 28 joints (DAS28), highLarsen score and seropositive rheumatoid factor (RF) as well as C-reactive protein (CRP).Patients with AG and GG genotypes demonstrated significant positive correlations between serum IL17 and DAS28.Meanwhile, serum IL17 levels and Larsen score had significant positive correlation only in GG patients.The use of different treatment regimens did not affect serum IL17 levels significantly in various genotypes. In conclusion, IL17 may be implicated in the pathogenesis of RA, being associated with a higher disease activity parameters, however, its action may be potentiated due to loss of the functional IL4RA allele (rs1805010), particularly in carriers ofthe GG genotype. Furthermore, determining the genetic variants of IL4R rs1805010 may be promising for identification of patients at risk worse prognosis. Key words:Autoimmune disease; pro-inflammatory cytokines;IL4Rgenotypes

Potential role of calprotectin as a monitoring biomarker for clinical and sonographic activity and treatment outcome in recent-onset rheumatoid arthritis

Background Calprotectin is a protein released during the activation and turnover of leukocytes. It can be used as a biomarker of inflammatory diseases such as rheumatoid arthritis (RA). Aim The current study aimed to measure the serum level of calprotectin in RA patients, recently diagnosed and after initiation of treatment, to determine its association with clinical disease, synovial inflammation determined by Ultrasound (US), and its relation to therapy when compared with other inflammatory markers. Patients and methods A total of 32 patients with recent RA and 20 healthy individuals were assessed for serum calprotectin level (enzyme-linked immunosorbent assay). C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were also measured in patients who were reassessed 4 months after initiation of therapy. Disease activity was evaluated by the disease activity score of 28 joints (DAS28), and US assessment was performed. Results The mean level of serum calprotectin was significantly higher (P<0.001) than that of controls. At baseline, there were significant (P<0.001) correlations of calprotectin serum level with DAS28, ESR, CRP, grayscale, and power Doppler (PD) synovitis scores. After therapy, all except DAS28 and ESR significantly correlated with calprotectin serum level. Calprotectin was shown to be better (P=0.001) than CRP (P=0.922) and ESR (P=0.104, r2=0.495) in predicting power Doppler synovitis score. Calprotectin results showed higher sensitivity in predicting disease activity at the stage of active inflammation. Conclusion Serum calprotectin level is strongly associated with clinical, laboratory, and US parameters of inflammation in recent-onset RA. Calprotectin is a confident biomarker for monitoring the treatment outcome in RA patients

In shoulder adhesive capsulitis, ultrasound-guided anterior hydrodilatation in rotator interval is more effective than posterior approach: A randomized controlled study

Abstract: Shoulder adhesive capsulitis, also called frozen shoulder, is a musculoskeletal disorder associated with pain and functional disability. This study aimed to compare the effectiveness of shoulder ultrasound-guided hydrodilatation with corticosteroid, via rotator interval (RI) anteriorly, versus posterior approach, in adhesive capsulitis patients. All patients received exercise program following injection. Patients and methods: A prospective randomized controlled study among 60 consecutive adhesive capsulitis patients was randomized into two equal groups. Group I received ultrasound-guided hydrodilatation with corticosteroid, saline, and local anesthetic via posterior intra-articular approach; group II received the same ultrasound-guided hydrodilatation via anterior rotator interval approach. Both groups received guided stretching exercises for 3 months after injection. Baseline and 3 months evaluation of pain by visual analogue scale (VAS), shoulder pain and disability index (SPADI), and range of motion (ROM) had been recorded for all patients. Results: Both groups showed significant improvement 3 months after hydrodilatation regarding VAS pain, external rotation, and SPADI. Only in group II (RI anterior approach) improvement was observed regarding flexion and abduction. There was no improvement regarding extension or internal rotation in either group. When comparing the improvement in both groups after hydrodilatation, group II (anterior approach) showed a statistically significant higher level of improvement regarding VAS pain (p = 0.003), SPADI, flexion, abduction, and external rotation, compared to group I (p < 0.001). Extension, internal rotation, and adduction were not different. Conclusions: Ultrasound-guided anterior rotator interval hydrodilatation for adhesive capsulitis, followed by guided exercise, is clinically and functionally more effective than the conventional posterior approach

Subclinical synovitis and enthesitis in psoriasis patients and controls by ultrasonography in Saudi Arabia; incidence of psoriatic arthritis during two years

Objective: To evaluate ultrasonographic subclinical inflammatory synovitis and enthesitis in psoriasis patients, without clinical arthritis or enthesitis compared with healthy controls, with a 2-year follow-up to study the associated incidence of psoriatic arthritis (PsA). Methods: A total of 109 consecutive psoriasis vulgaris patients without clinical signs of PsA and 90 healthy controls were included from two tertiary medical centers. Subjects underwent dermatological examination, PASI score evaluation for severity of psoriasis, musculoskeletal examination using 68/66 joints count for tenderness and swollen joints. Patients were assessed for CRP, musculoskeletal ultrasound (MSUS) in the form of grayscale ultrasound (GSUS), and power Doppler ultrasound (PDUS) for eight entheses and 34 joints to detect MSUS subclinical enthesitis and synovitis. All patients were followed-up for 2 years to detect evolving PsA. Results: Subclinical enthesitis and synovitis were detected in 39.5% of psoriasis patients and 10% of controls (P < 0.001). CRP was significantly higher in psoriasis patients with MSUS manifestations (P < 0.01). PDUS and GSUS subclinical synovitis and/or enthesitis were detected at least in one site in psoriatic patients more than in controls (P < 0.05). During a 2-year follow-up of patients, the annual PsA incidence was 4.3%. Psoriasis patients who developed PsA showed a higher prevalence of baseline enthesitis, higher PDUS and GSUS synovitis scores, and higher baseline CRP level than those who did not develop PsA. Conclusions: MSUS subclinical synovitis and enthesitis are quite common in psoriasis patients. The incidence of PsA in Saudi’s psoriasis patients was slightly higher than worldwide reports. Subclinical enthesitis, PDUS, and GSUS synovitis could predict PsA development

Impact of sustained remission on quality of life among women with rheumatoid arthritis and systemic lupus erythematosus: a prospective observational study

Abstract Background Health-related quality of life (HRQOL) as a patient reported outcome plays important roles in the life of patients with RA (rheumatoid arthritis) and SLE (Systemic lupus erythematosus) as well as their families. Evaluating the impact of sustained remission on HRQOL is important and could be of potential help in daily practice. Thus, we aimed to assess and compare prospectively the impact of sustained remission on HRQOL in Saudi RA and SLE female cohorts. Results Sixty-two female patients with active RA and 34 female patients with active SLE fulfilled the inclusion-, entry- and follow-up criteria. At baseline, the SLE patients had significantly better SF-36 scores than the RA patients. In both groups, significant correlations were found between disease activity and physical (PCS) and mental (MCS) components summary of the SF-36 (all p’s ≤ 0.001). In sustained remission, both SLE and RA patients showed significant improvements of the SF-36 scores (p < 0.001) compared to baseline. RA patients in sustained remission had a significantly better general health, bodily pain and physical functioning, and total PCS scores (p < 0.001) than those with SLE. Conclusions Both SLE and RA patients in sustained remission showed strongly improved HRQOL. In sustained remission, RA patients had comparable or better HRQOL than SLE patients

The clinical musculoskeletal ultrasonography: Egyptian guidelines for structured musculoskeletal ultrasound scanning and reporting

Abstract Background The aim of this work is to set up the standards for performing musculoskeletal ultrasound scans and reporting as an additional procedure in the rheumatology setting. We used two rounds of the Delphi approach to get the consensus on a musculoskeletal ultrasound reporting. Results Fifteen expert panels had completed the two rounds of surveys. After the end of round two, eighteen recommendations distributed upon eight domains were released. The percentage of the agreement on the recommendations was 93.3 to 100 %. All eighteen key questions were answered at the end of the second round with agreement. Conclusion A musculoskeletal ultrasound report template has been developed by this study, based on outcomes of a Delphi process, by an international participants’ panel. All domains met the 80% voting threshold set in this work. The reporting template can be used for both clinical research as well as standard practice to provide guidance and standardize the musculoskeletal ultrasound reporting