Publications by authors named "Hanan Darweesh"

6 Publications

  • Page 1 of 1

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

Hum Immunol 2015 Jun 7;76(6):417-20. Epub 2015 Apr 7.

Department of Clinical and Chemical Pathology, Faculty of Medicine, Kasr El Ani Hospital, Cairo University, Egypt.

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 Crohn's (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.
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June 2015

Association between TNF promoter -308 G>A and LTA 252 A>G polymorphisms and systemic lupus erythematosus.

Mol Biol Rep 2014 14;41(4):2029-36. Epub 2014 Jan 14.

Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Giza, Egypt.

Tumor necrosis factor (TNF) and lymphotoxin alpha (LTA) are pivotal cytokines in the pathogenesis of systemic lupus erythematosus (SLE). To investigate the possible association of the polymorphism of the TNF promoter gene -308 and that of the LTA gene 252 with susceptibility to SLE and with phenotypic disease features in Egyptian patients. A case control study involving 100 SLE patients and 100 unrelated healthy controls. Polymerase chain reaction and restriction fragment length polymorphism methods were applied to detect genetic polymorphism. We found that TNF-308 genotype AA was significantly increase by 26 % in SLE patients compared to 10 % in the control group (p = 0.003; OR 3.16; CI 1.43-6.98) and the frequency of the A allele of the TNF promoter -308 was significantly higher in the SLE patients (42 %) than in the control subjects (24 %) (p < 0.001; OR 2.29; 95 % CI 1.49-3.52). Genotype LTA 252 GG showed a significant increase by 22 % in SLE patients compared to 6 % in the control group (p = 0.001; OR 4.42; 95 % CI 1.71-11.44), and the frequency of the G allele of the LTA was significantly higher in the SLE patients (38 %) than in the control subjects (21 %) (p < 0.001; OR 2.31; 95 % CI 1.48-3.6). Genotype (AA+GA) of TNF was significantly associated with clinical manifestations as malar rash, arthritis, oral ulcers, serositis and systemic lupus erythematosus disease activity index. Genotype (GG+GA) of LTA was significantly associated with arthritis. These results suggest that TNF and LTA genetic polymorphisms contribute to SLE susceptibility in the Egyptian population and are associated with disease characteristics. TNF-308 and LTA+252 polymorphic markers may be used for early diagnosis of SLE and early prediction of clinical manifestations, like arthritis.
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December 2014

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

Immunol Invest 2012 18;41(8):864-75. Epub 2012 Sep 18.

Medical Biochemistry and Molecular Biology, Cairo University , Cairo , Egypt.

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.
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May 2013

Knee enthesitis and synovitis on magnetic resonance imaging in patients with psoriasis without arthritic symptoms.

J Rheumatol 2012 Oct 1;39(10):1979-86. Epub 2012 Aug 1.

Rheumatology and Rehabilitation Department, Radiology Department, Orthopedic Department, and Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

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.
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October 2012

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.

J Clin Immunol 2011 Oct 21;31(5):848-56. Epub 2011 Jun 21.

Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt.

Objective: This 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 Methods: In 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.

Results: Significantly 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).

Conclusions: Urinary 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.
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October 2011

Enthesitis in seronegative spondyloarthropathies with special attention to the knee joint by MRI: a step forward toward understanding disease pathogenesis.

Clin Rheumatol 2011 Mar 6;30(3):313-22. Epub 2011 Jan 6.

Radiology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

Seronegative spondyloarthropathies are a unique group of disorders sharing similar clinical characteristics (e.g., inflammatory back pain, spondylitis, sacroiliitis, uveitis, inflammatory bowel disease, skin rashes, and enthesitis). Clinical and genetic similarities suggest that they also share similar causes or pathophysiologies. Rheumatoid factor (RF) is characteristically negative in this group of disorders, hence collectively termed seronegative spondyloarthropathies (SpA). They include psoriatic arthritis, ankylosing spondylitis, reactive arthritis, ulcerative colitis, and Crohn's disease. "Enthesitis", the term used to describe inflammation at tendon, ligament, or joint capsule insertions, is considered a common feature in this domain and was included in the European Spondyloarthropathy Study Group criteria for the classification of SpA. Evaluation of entheseal-related changes at different joints by MRI became an important item on the research agenda in both differentiated and undifferentiated arthritis. Most of the research focused on MRI findings in the hand and wrist joints among patients with RA and SpA and support two patterns of inflammation "RA" phenotype where synovial involvement is the primary target of inflammation and "SpA" pattern where enthesitis comes first followed by synovitis. In this review, we summarize the literature on enthesitis in SpA and focus on MRI findings in the knee joint in the SpA group of disorders and subclinical synovitis among patients with skin psoriasis.
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March 2011