Hanan Darweesh

Correlations of Urinary Biomarkers, TNF-Like Weak Inducer of Apoptosis (TWEAK), Osteoprotegerin (OPG), Monocyte Chemoattractant Protein-1 (MCP-1), and IL-8 with Lupus Nephritis

ObjectiveThis case-controlled study was designed to correlate urinary biomarkers, TNF-like weak inducer of apoptosis (TWEAK), osteoprotegerin (OPG), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) levels, with renal involvement in a cohort of systemic lupus erythematosus (SLE) patients to examine their diagnostic performance.Patients and MethodsIn 73 SLE patients, and in 23 healthy volunteers, urinary levels of TWEAK, OPG, MCP-1, and IL-8 levels were measured. Disease activity was assessed by total SLE disease activity index, and renal activity by renal activity index (rSLEDAI), and both were correlated with urinary biomarkers. Sensitivity, specificity, and predictive values of individual biomarkers to predict lupus nephritis were also calculated.ResultsSignificantly higher levels of urinary biomarkers were observed in SLE patients with lupus nephritis (LN) compared with those without LN (TWEAK, p < 0.001; MCP-1, p < 0.001; OPG, p < 0.001; IL-8, p < 0.032). Other significantly higher levels were observed in SLE patients with LN compared with control subjects (TWEAK, MCP-1, OPG, and IL-8 p < 0.001). Positive correlations were observed between rSLEDAI and TWEAK (r = 0.612 and p < 0.001), MCP-1 (r = 0.635 and p < 0.001), and OPG (r = 0.505 and p < 0.001).ConclusionsUrinary levels of TWEAK, OPG, and MCP-1 positively correlate with renal involvement as assessed by rSLEDAI with reasonable sensitivity, specificity, and predictive values to detect lupus nephritis while IL-8 was not significantly associated with global or rSLEDAI.

Raised serum level of APRIL in patients with systemic lupus erythematosus: correlations with disease activity indices.

The aim of the present study is to assess serum APRIL levels in SLE patients versus rheumatoid arthritis (RA) patients and normal control and to correlate serum APRIL levels in SLE patients with disease activity indices. Serum APRIL levels was measured in 40 SLE patients, 20 patients with RA and 20 healthy volunteers who served as control group. Disease activity in SLE patients was assessed by the British Isles Lupus Assessment Group (BILAG) index and SLE disease activity index (SLEDAI), and results were correlated with serum APRIL levels. Significantly higher serum APRIL levels was observed in SLE patients compared to RA patients and normal controls (p=0.003 and p < or = 0.001, respectively). Positive correlations were found between serum APRIL levels and total BILAG index (r=0.486 and p=0.001), BILAG musculoskeletal score (r=0.848 and p < or = 0.001) and BILAG cardiorespiratory score (r=0.326 and 0.04). Serum APRIL was higher in SLE patients compared to RA patients and normal control subjects and positively correlates with BILAG index and higher levels may be associated with musculoskeletal manifestations of the disease. APRIL antagonism could be a potential therapeutic target in SLE.

Knee Enthesitis and Synovitis on Magnetic Resonance Imaging in Patients with Psoriasis without Arthritic Symptoms

Objective. This case-control study was designed to evaluate magnetic resonance imaging (MRI) findings of knee joints in patients with psoriasis without clinical peripheral or axial joint involvement, and to correlate MRI findings with disease and demographic variables. Methods. In total 48 patients with psoriasis and no clinical evidence of synovitis or enthesitis in any peripheral or axial joints were enrolled. A random sample of 20 healthy subjects without knee or other joint complaints and matched for age and sex served as controls. All patients and controls underwent enhanced MRI studies of both knee joints, and MRI findings were compared. Results. Among 48 patients (96 knees), a total of 90 entheseal lesions were detected, with no enthesitis in 2 cases (6.3%). Signs of continuing inflammation bilaterally were frequently found: soft tissue edema (STE; n = 52), bone marrow edema (BME; n = 20), perientheseal BME (n = 3), cartilaginous erosions (n = 42), and bone erosions (n = 27). In controls, 2 (10%) subjects had BME and another 5 (25%) showed cartilaginous erosions. None showed evidence of enthesitis. Significant correlations were observed between the number of entheseal lesions of both knees vs STE (present vs absent; r = 0.314, p = 0.030) and STE (number of lesions; r = 0.351, p = 0.014). Enthesitis (unilateral vs bilateral) was significantly and positively correlated with STE (r = 0.304, p = 0.036), cartilaginous erosions (r = 0.304, p = 0.036), and villous projections (r = 0.347, p = 0.016). Conclusion. Subclinical synovitis and enthesitis are frequently found in the knee joint of patients with psoriasis. These may be an early sign of psoriatic arthritis.

Evidence of association of interleukin-23 receptor gene polymorphisms with Egyptian rheumatoid arthritis patients.

BACKGROUND The identification of additional genetic risk factor is an on-going process that will aid in the understanding of rheumatoid arthritis (RA) aetiology. A genome-wide association scan in Crohns (CD) disease highlighted the interleukin-23 receptor (IL23R) gene as a susceptibility factor. Since the IL-23/IL-17 pathway is known to associate with other autoimmune disease, including rheumatoid arthritis and systemic sclerosis, we hypothesised that IL23R could be a shared susceptibility gene. The rare allele of IL23R single nucleotide polymorphism (SNP) rs11209026 (Arg381Gln) confers strong protection against CD. Our aim was to analyse IL23R SNP (rs11209026, rs2201841, and rs10889677) and to detect its association with RA in Egyptian patients. METHODS A group of Egyptian patients with RA (n=120) and apparently healthy persons as controls (n=120) was genotyped for rs11209026, rs2201841 and rs10889677 by real time/polymerase chain reaction (real-time/PCR) for the first SNP and restriction fragment length polymorphism/PCR (RFLP/PCR) in the last two SNPs. RESULTS Our data emphasise that the AA genotype of rs11209026 (Arg381Gln) was significantly associated with RA patients compared to the controls (P value=0.001).We did not find any significant association between either rs2201841 or rs10889677 and the development of rheumatoid arthritis (P value=1.000 & 0.562 respectively). CONCLUSION Our results suggest that IL23 receptor AA genotype variant of rs11209026 would contribute to RA aetiology; consequently, it might be a genetic marker for RA. We need to address the subgroup of patients who will benefit from the selective suppression of the IL23 signalling which would represent new perspectives toward a personalized therapy of RA patients by further studies.

The Tie2 receptor antagonist angiopoietin-2 in systemic lupus erythematosus: its correlation with various disease activity parameters.

Background: Systemic lupus erythematosus is one of the autoimmune diseases characterized by multisystem involvement associated with autoantibody and immune complex vasculitis along with endothelial cell damage. Objective: to study the possible role of Angiopoietin- 2 (Ang-2) as a recently highlighted inflammatory and angiogenic mediator in the pathogenesis of SLE and its correlation with the state of another inflammatory marker, P-Selectin, as well as with various markers of the disease activity. Patients and methods: The present study included 3 main groups: active SLE patients (group I), inactive SLE patients (group II) and healthy normal control subjects (group III). Groups I and II were subjected to disease activity assessment using the SLEDAI scoring system and measurement of plasma Ang-2 and P-Selectin by ELISA in addition to various laboratory investigations to assess disease activity as: Complete blood count, ESR, serum creatinine, C3, C4 and 24-h urinary proteins. Results: The mean level of Plasma Ang-2 and P-selectin showed a high significant increase in active group compared to inactive SLE patients and control subjects (p < 0.001).There was a significant positive correlation between Ang-2, P-Selectin, and each of SLEDAI score and 24-h urinary proteins in all SLE patients as well as in the active group, and Ang-2 was a significant independent marker for proteinuria. A significant negative correlation was found between Ang-2, P-Selectin and each of C3, C4. Ang-2 and P-Selectin showed a high sensitivity and specificity in the patients with SLE. Conclusion: Our study suggests that Ang-2 may be a more useful marker than P-Selectin, C3 and C4 in the assessment of disease activity.

Serum and synovial cartilage oligomeric matrix protein (COMP) in patients with rheumatoid arthritis and osteoarthritis

Abstract Objective To measure serum and synovial COMP levels in rheumatoid arthritis (RA) and osteoarthritis (OA) patients and to assess their correlation with clinical, laboratory and ultrasonographic parameters. Methods Two groups of patients were included in this study consisting of 32 patients with RA and 10 patients with knee OA. Ultrasonography of knee joints was performed and serum and synovial Cartilage oligomeric matrix protein (COMP) levels were measured using an inhibition ELISA. Results The mean synovial COMP level was significantly higher in RA compared to OA patients (14.3 ± 5.19μg/mL and 9.26 ±2.42 μg/mL respectively, P Conclusion The synovial COMP and ultrasonographic joint evaluation may be considered as markers of disease activity and cartilage destruction in both RA and OA patients.

Association of Urotensin II Gene Polymorphism with Disease Pattern in Systemic Sclerosis Patients

Background: Urotensin II (U-II) and its receptor, UT, are widely expressed throughout the body. It is known to be the most potent endogenous vasoconstrictor discovered to date. Its physiological mechanisms are similar in some ways to Endothelin 1 (ET-1). Objective: To investigate the possible association of the polymorphism of UTS2 gene (Thr21Met and Ser89Asn) with the susceptibility to SSc and pattern of disease manifestations in Egyptian patients. Results: We found that the Thr21Met MM genotypes of the UTS2 gene were significantly increased in SSc patients (20%) compared to the control subjects (5%) (p=0.013) There was a significant difference in the MM and NN genotypes in diffuse SSc patients (35.7%, 67.9%) compared to limited SSc patients (6.2%, 25%) (p=0.004, 0.001) .The frequency of the N allele of the UT89 gene polymorphism was significantly higher in the SSc patients (58.3%) than in the control subjects (36.7%) (p=0.001). Significant associations were found between Thr21Met MM and Ser89Asn NN genotypes with pitting scars, digital ischemia, pulmonary hypertension, gastrointestinal manifestations and Anti Scleroderma-70 Antibody. Significant associations were found between Thr21Met M allele with pitting scars, digital ischemia and Anti Scleroderma-70 Antibody, while Ser89Asn N allele showed also in addition a significant association with Raynauds phenomenon and renal manifestations. Conclusion: The results suggest that UTS2 Thr21Met and Ser89Asn genetic polymorphisms may be important risk factors in the development of SSc susceptibility in the Egyptian population, and an indicator of many disease manifestations such as pulmonary hypertension, severe skin and lung involvement in patients with SSc.

Antibodies to extractable nuclear antigens (ENAS) in systemic lupus erythematosus patients: correlations with clinical manifestations and disease activity

The aim was to explore possible correlations of antibodies to extractable nuclear antigens (ENA) with clinical manifestations and disease activity indices in systemic lupus erythematosus (SLE) patients. A total of 70 consecutive SLE patients (64 females) were included. Disease activity was assessed by SLE activity index (SLEDAI), and British Isles Lupus Assessment Group (BILAG). Anti-Ro/SSA correlated positively with, headache (r=0.24, p=0.04), blurring of vision (r=0.25, p=0.03) and SLEDAI (r=0.25, p=0.04) and negatively with C3 (r=-0.35, p=0.003). Anti-Ro/SSA correlated with anti La/SSB antibodies (r=0.69, p<0.001), but not with anti-DNA, anti-RNP and anti-Sm antibodies. Anti-La/SSB antibodies correlated with headache (r=0.26, p=0.03), SLEDAI (r=0.25, p=0.03) and negatively with C3 (r=-0.34, p=0.004). Anti-La/SSB did not correlate with anti-RNP or anti-Sm antibodies. Anti-Sm antibodies correlated with disease duration (r=0.34, p=0.003), 24 hours urinary proteins (r=0.31, p=0.008), SLEDAI (r=0.31, p=0.009), BILAG renal score (r=0.29, p=0.02) and negatively with age at onset (r=-0.27, p=0.02), WBCs (r=-0.29, p=0.014) and C4 (r=-0.25, p=0.049). In multivariate analyses, anti-Ro/SSA antibodies remained associated with headache, blurring of vision and C3 and anti-La/SSB antibodies remained associated with C3 and with headache. Anti-Sm antibodies were independently associated with disease duration and total SLEDAI scores, while anti-RNP antibodies remained significantly associated with BILAG mucocutaneous scores only. Antibodies to ENAs are associated with clinical aspects of SLE and may play a role in the assessment of disease activity. Insight into these ENAs may lead to new approaches to diagnostic testing, accurate evaluation of disease activity and lead to target approach for SLE.