TNF-α versus IL-6 Genes Expression levels in Active Rheumatoid Arthritis: Clinical and Laboratory Determinants.

This study intended to compare the expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) genes in active rheumatoid arthritis (RA) patients who were receiving conventional synthetic disease-modifying drugs (csDMARDs) and to find the clinical and laboratory determinants affecting TNF-α and IL-6 genes expression levels among active RA patients. This was a cross sectional study that included 108 active RA patients who were receiving csDMARDs. A detailed history was reviewed for all patients in addition to a complete physical examination and assessment of the 28-joint disease activity score (DAS28). Some laboratory measures were recorded as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and serum rheumatoid factor (RF). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure expression levels of TNF- α and IL-6 genes. In active RA patients, TNF-α and IL-6 genes expression levels were significantly correlated to each other (p<0.001, r=0.788). Also, both had positive correlations with the age and DAS28 among RA patients (p<0.001). IL-6 and TNF-α expression levels were significantly higher in RA patients with high DAS28 scores (p<0.001). Most RA patients (81.5%) had relatively higher IL-6 gene expression levels than TNF-α. RA patients with relatively high IL-6 expression levels were younger in age and had shorter disease duration and less DAS28 than RA patients with relatively high TNF-α gene expression levels. In addition, they had higher CRP and RF levels. Young age was detected as a significant predictor for relatively higher IL-6 gene expression levels than TNF-α. In conclusion, most active RA patients had higher IL-6 gene expression levels than TNF-α. Young age could be considered a significant predictor for relatively high IL-6 gene expression levels among active RA patients.

Plasma Wnt7b protein in rheumatoid arthritis: Detection of interstitial lung disease.

OBJECTIVE: To determine the plasma level of Wingless-related integration site 7b (Wnt7b) protein in rheumatoid arthritis (RA) patients (with and without interstitial lung disease (ILD)) and in idiopathic pulmonary fibrosis (IPF) patients and its relationship with RA disease activity and/or severity of pulmonary fibrosis. To assess the validity of plasma Wnt7b for the detection of ILD among RA patients. METHOD: This case-control study included 128 subjects (32 RA-ILD, 32 RA, 32 IPF, and 32 healthy controls). RA and RA-ILD Patients were evaluated for disease activity by DAS28 and disease activity grades were recorded according to DAS28 grades. Laboratory parameters as Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Rheumatoid Factor (RF), Anti-citrullinated peptide (Anti-CCP) were recorded. Plasma Wnt7b levels were measured by ELISA. Diagnosis of pulmonary fibrosis (for RA-ILD and IPF patients) was done by high resolution computed tomography (HRCT) and its severity was assessed mainly by pulmonary function test using forced vital capacity (FVC) grading. RESULTS: Comparison of Wnt7b plasma levels showed a significant difference between the studied groups with the P-value < 0.018 (RA-ILD had the highest levels). Post hoc analysis revealed a significant difference in Wnt7b plasma levels between RA-ILD and IPF groups (P = 0.008). Also, RA-ILD and control groups had a significant difference (P = 0.039). However, there was a non-significant relationship between Wnt7b plasma levels and RA disease activity as well as the severity of pulmonary fibrosis. ROC curve analysis for the plasma Wnt7b levels revealed that a level  ≥285.1 pg/ml had a sensitivity of 87.5% and a specificity of 43.8% for the detection of ILD in RA patients with positive likelihood ratio of 1.56 and negative likelihood ratio of 0.29. CONCLUSION: RA-ILD patients had significantly higher plasma Wnt7b levels than the controls and IPF patients. These data suggest that the Wnt7b secretion is augmented by the concomitant presence of RA with pulmonary fibrosis. In addition, plasma Wnt7b may be used as a highly sensitive test for the detection of immunologically induced fibrotic changes in lung tissue among RA patients.

Damage accrual in Behçet disease: Behçet's Syndrome Overall Damage Index (BODI) versus Behçet's Disease Damage Index (BDI).

OBJECTIVES: To assess the validity of Behçet's Syndrome Overall Damage Index (BODI) and Behçet's Disease Damage Index (BDI) as tools for the detection of damage accrual in Behçet's patients compared to Vasculitis Damage Index (VDI). Also, to evaluate the correlation and the interclass correlation among the 3 indices to find out their consistency. METHOD: A prospective cohort study was carried out on 102 adult Behçet's disease (BD) patients who were diagnosed according to the International Study Group criteria for BD. Disease severity and organ damage were assessed for each patient by VDI, BDI and BODI at baseline and 1-year follow-up visits. Damage accrual for each index was defined when there was an increase of at least 1 point (∆ ≥ 1) among the baseline and the follow-up visits. RESULTS: Correlations among the 3 indices were significant, with (r = 0.835, P < 0.001) between VDI and BODI, (r = 0.835, P < 0.001) between VDI and BDI, and (r = 0.844, P < 0.001) between BODI and BDI scores. A highly significant positive correlation existed between the 3 indices and age and disease duration. In contrast, the correlation with the BD Current Activity Form was non-significant, which indicates good discriminative validity of the 3 indices. Neuropsychiatric and ocular systems showed a strong interclass correlation among the 3 indices. Regarding detecting damage accrual, BDI was more sensitive than BODI and showed more agreement with VDI. CONCLUSION: BD damage indices, VDI, BODI and BDI, had good convergent and discriminative validity for the assessment of BD damage. BDI had more sensitivity than BODI to the detection of damage accrual.

Workplace activity limitation and quality of life: A study on rheumatoid arthritis patients.

BACKGROUND: Rheumatoid arthritis (RA) causes disabilities that affect people in working age and can impair their working activity and quality of life (QoL). OBJECTIVES: To assess work activity limitation and QoL among RA patients and to explore the associated risk factors. METHODS: A cross-sectional study on 344 RA patients was conducted at the outpatient clinic using a number of standardized questionnaires including the Health Assessment Questionnaire Disability Index, Workplace Activity Limitation Scale, and RA QoL. Clinical examinations were also performed including the measurement of pain intensity, assessment of disease activity, and the Rheumatoid Arthritis Severity Scale. RESULTS: Most of the employed participants (87%) experienced high work activity limitations. Increasing work limitations were significantly associated with a decrease in QoL domains scores. The most significant risk factors affecting work limitation by logistic regression were high disease activity, the severity of the disease, married females, and a high health assessment disability index among RA patients. CONCLUSIONS: RA patients experience limitations that affect their productivity at work and their QoL. Paying more attention to early management to prevent the upcoming unfavorable health and economic consequences for RA patients is significantly important.

Validity of immunoglobulin-binding protein 1 as a biomarker for lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is a major issue that adds a burden on patients with systemic lupus erythematosus (SLE). Immunoglobulin-binding protein 1 (IGBP1) is identified as a phosphoprotein that has been recently reported to be linked to the B-cell receptor complex and regulates differentiation, proliferation, apoptosis, and tolerance of B cells. Its diagnostic and/or prognostic role in LN has been highlighted only recently. OBJECTIVES: This study aims to evaluate the relation between serum IGBP1 and SLE disease activity and/or renal activity and to investigate the validity of IGBP1 as a biomarker for LN. METHODS: 96 participants were enrolled and divided into three groups: nephritis, nonnephritis, and control groups. The patients with SLE were diagnosed according to the Systemic Lupus International Collaborating Clinics classification (SLICC) criteria. The serum IGBP1 level was assayed using an enzyme-linked immunosorbent assay (ELISA). Assessments were conducted using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2k) and renal biopsy for LN patients. RESULTS: The nephritis and nonnephritis groups had higher IGBP1 levels than the controls; the nephritis group had the highest serum IGBP1 levels (p < .001). Significant correlations were found between IGBP1 levels and proteinuria (r = 0.568, p = .001) and renal SLEDAI (r = 0.475, p = .006) in the nephritis group; on the other hand, the correlation of serum IGBP1 levels with SLEDAI-2K was non-significant for both groups (nephritis and nonnephritis groups). The IGBP1 levels were significantly different among histopathologic classes (p < .001), with class V showing the highest level. Moreover, it showed a significant positive correlation with the pathologic activity index. Compared with renal SLEDAI for identifying active renal affection in patients with SLE, the serum IGBP1 level with a cut-off value of 547.45 ng/mL is a valid biomarker for detecting active nephritis with 93.8% sensitivity and 96.9% specificity. CONCLUSION: The serum IGBP1 levels were high in patients with LN and were positively correlated with the pathologic activity index. The serum IGBP1 level of 547.45 ng/mL is a valid biomarker for detecting active nephritis. Thus, we recommend that clinicians monitor the serum IGBP1 level of patients with SLE to detect LN.

Validity of systemic lupus erythematosus disease activity score (SLE-DAS) for definition of lupus low disease activity state (LLDAS).

INTRODUCTION: SLE disease activity score (SLE-DAS) is a novel, rapid, continuous and comprehensive score that overcomes the drawbacks of SLEDAI-2 K. Low lupus disease activity state (LLDAS) has been targeted as an endpoint in many clinical trials and as a favourable outcome in clinical practice. Therefore, our objective in the current study is to evaluate the validity of SLE-DAS for defining LLDAS as an objective in the treat-to-target strategy. METHODS: A cross-sectional study was carried out on 117 SLE patients who were diagnosed according to Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE. Patients were evaluated for disease activity by both SLEDAI-2 K and SLE-DAS. Additionally, patients were divided according to the SLEDAI-2 K-derived LLDAS definition into two groups: low disease activity (LDA) group and high disease activity (HDA) group. The validity of SLE-DAS for the definition of LLDAS was evaluated in comparison to SLEDAI-2 K. RESULTS: SLE-DAS shows highly significant positive correlation (r = 0.743, p < 0.001) with SLEDAI-2 K. The ROC curve revealed that SLE-DAS is valid for the assessment of activity with the best detection of LLDAS was at 6.62 with 95.5% sensitivity, 79.3% specificity and 89.6% accuracy. Moreover, it had a good agreement with the SLEDAI-2 K-derived definition of LLDAS (k = 0.765, p < 0.001). CONCLUSION: SLE-DAS is a valid score for the definition of LLDAS which can be used in the clinical practice as a simple and precise standalone criterion. Key Points • Correlation between SLEDAI-2K and SLE-DAS revealed a high significance. • Identify SLE-DAS cut-off 6.62 for the definition of LLDAS. • There is a good agreement between SLEDAI-2K-derived definition of LLDAS and SLE-DAS definition.