Abir N Mokbel

Homing and reparative effect of intra-articular injection of autologus mesenchymal stem cells in osteoarthritic animal model

AbstractBackgroundThis work aimed to study the homing evidence and the reparative effect of mesenchymal stem cells (MSCs) in the healing process of induced osteoarthritis in experimental animal model (donkeys).MethodsTwenty-seven donkeys were equally divided into 3 groups based on the observation period after induction of arthritis (3, 6 and 9 weeks) to achieve different degrees of osteoarthritis. Each group was subdivided into three subgroups of three animals each based on the follow-up period (1, 2 and 6 months) after treatment. The induction was done through intra-articular (IA) injection of 2 ml of Amphotericin-B in both carpal joints. MSCs were harvested in a separate procedure, labeled with green fluorescent protein (GFP) using monster GFP vector and suspended in hyaluronic acid for IA injection. Treatment approaches consisted of cell-treatment using MSCs suspended in 3 ml of hyaluronic acid (HA) for the right carpal joint; and using the same amount of (HA) but without MSCs for the left contralateral carpal joint to serve as a control. Animals were assessed clinically and radiologically before and after treatment. Synovial fluid was also evaluated. Histopathologically; articular cartilage structural changes, reduction of articular cartilage matrix staining, osteophyte formation, and subchondral bone plate thickening were graded. Data was summarized using median and percentile for scores of histopathologic grading. Comparison between groups was done using non-parametric Mann Whitney test.ResultsThe reparative effect of MSCs was significant both clinically and radiologically in all treated groups (P < 0.05) compared to the control groups. Fluorescence microscopy of sections of the cell-treated joints of all animals indicated that the GFP-transduced injected cells have participated effectively in the reparative process of the damaged articular surface and have integrated within the existing articular cartilage. The cells were associated with the surface of the cartilage and, were also detected in the interior.ConclusionsHoming was confirmed by the incorporation of injected GFP-labeled MSCs within the repaired newly formed cartilage. Significant recovery proves that the use of IA injection of autologous MSCs is a viable and a practical option for treating different degrees of osteoarthritis. http://www.biomedcentral.com/1741-7015/10/44/abstract

Damage index in childhood-onset systemic lupus erythematosus in Egypt

BackgroundTo investigate the prevalence of cumulative organ damage among Egyptian children with juvenile-onset systemic lupus erythematosus (jSLE) and the relationships between the organ damage and the demographic data, clinical variables, and disease activity.MethodsA total of 148 patients with jSLE have been followed in the pediatric rheumatology clinic and section at Cairo University. These patients were evaluated by retrospective chart review. The organ system damage due to SLE was measured using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Risk factors for damage were also studied including demographic criteria as well as clinical and laboratory manifestations.ResultsOverall, 43.9% of the patients had damage within a mean of 6.57 ± 3.59 years of disease diagnosis. Neuropsychiatric (NPS-21%) and renal (16.9%) system involvement were observed most frequently, followed by cardiovascular (11.5%), skin (9.5%), pulmonary (6.1%), and ocular (4.8%), with a mean SDI score of 0.93 ± 1.37. In our study, the presence of neuropsychiatric manifestations at diagnosis showed the strongest association with the presence of later disease damage.The number of SLE diagnostic criteria at presentation was strongly associated with the total SDI score, and the renal damage was significantly more prevalent in patients with age at disease diagnosis below 10 years of age. A higher mean disease duration was found in patients with musculoskeletal damage.ConclusionWe found that cumulative organ damage, as measured by the SDI, was present in 43.9% of Egyptian patients with juvenile-onset SLE. The damage was significantly more likely in patients who had more SLE diagnostic criteria at time of disease presentation and NPS manifestations at the time of diagnosis.

Interleukin-17 in Behçet's disease: relation with clinical picture and disease activity

Aim The aim of this study was to assess serum levels of interleukin-17 (IL-17) in patients with Behçet′s disease (BD) and to evaluate its relation to the clinical picture and disease activity. Patients and methods This case-control study was carried out on 38 patients with BD. A total of 20 age-matched and sex-matched healthy volunteers serving as the control group were also enrolled in this study. All patients were subjected to full history taking, thorough clinical examination, and clinical activity assessment using Behçet′s Disease Current Activity Form. Serum IL-17 levels were measured with enzyme-linked immunosorbent assay. Results Serum IL-17 levels were significantly elevated among BD patients. Patients with ocular involvement had higher IL-17 levels compared with those without; however, the difference did not reach statistical significance. Patients with neurological involvement had significantly higher IL-17 levels in their serum compared with those without neurological involvement and controls. Twenty-seven patients had active disease, whereas 11 patients had inactive disease. Serum IL-17 levels were significantly elevated in active BD patients. Patients with and without activity showed highly significant rise in IL-17 levels compared with healthy controls. There was no significant correlation between the amount of corticosteroids or colchicine being used and serum IL-17 levels. Conclusion IL-17 is elevated among BD patients and further increased with activity, ocular affection, and neuroinvolvement. Our findings suggest that IL-17 exerts an important role in the pathogenesis of BD, thus providing a promising target for novel therapy.

Thrombotic microangiopathy in lupus nephritis patients

Objective The aim of the present study was to evaluate the impact of thrombotic microangiopathy (TMA) on renal involvement in patients with lupus nephritis (LN). Patients and methods This study included 50 systemic lupus erythematosus patients with LN who had been referred for renal biopsy. Patients underwent clinical and laboratory assessment for disease activity and damage. The biopsy specimens were classified according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, activity and chronicity indices, and assessed for renal TMA lesions. Results TMA was found in 7/50 LN patients (14%). Patients with TMA lesions had significantly higher systolic and diastolic blood pressure (P = 0.018 and 0.019, respectively), higher serum creatinine (P = 0.031), lower estimated glomerular filtration rate (P = 0.023) and higher consumption of C3 (P = 0.002) than that of those without TMA lesions. Lupus anticoagulant positivity was significantly more frequent in patients with TMA (P = 0.001). There was a significant association between the detection of TMA and LN class IV. LN patients with TMA had significantly higher renal activity indices (P = 0.022). Chronicity index was higher in patients with TMA, but it did not reach a statistical significance. Conclusion TMA is not an uncommon vascular change in patients with LN, especially in those with diffuse proliferative glomerulonephritis (class IV LN). It is associated with lupus anticoagulant positivity, C3 hypocomplentemia and higher renal biopsy activity index. TMA was significantly associated with renal impairment and systemic hypertension. Thus, TMA may be an important cause of renal injury and renal dysfunction in a subset of patients with LN, a histological entity associated with worse renal prognosis.

Renal histopathological changes and clinical characteristics of antiphospholipid nephropathy in lupus nephritis patients

Objective The aim of the present study was to evaluate the renal histopathological changes and clinical characteristics associated with antiphospholipid nephropathy (APSN) in lupus nephritis (LN) patients. Patients and methods This study included 50 LN patients referred for renal biopsy. Patients underwent clinical and laboratory assessments for disease activity and damage. The biopsy specimens were classified according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, activity, and chronicity indices, and assessed for renal vascular lesions of APSN - acute (thrombotic microangiopathy) and chronic (fibrous intimal hyperplasia, fibrous arterial/arteriolar occlusion and focal cortical atrophy). Results APSN lesions were found in 17/50 patients (34%); furthermore, 7/50 patients (14%) had thrombotic microangiopathy lesions, whereas chronic APSN lesions were detected in 15/50 patients (30%). LN patients with APSN had significantly higher age and Systemic Lupus International Collaborating Clinics scores (P = 0.032 and 0.004, respectively), but there were no differences in renal and antiphospholipid syndrome manifestations. Lupus anticoagulant positivity was significantly more frequent in patients with APSN (P = 0.002). LN patients with APSN had significantly higher renal chronicity scores (P = 0.033) with more frequent interstitial fibrosis and tubular atrophy (P = 0.006 for each). There was no significant difference in the distribution of LN classes in patients with and without APSN. Conclusion APSN is frequently found in LN patients irrespective of the LN class and antiphospholipid syndrome manifestations. It is associated with lupus anticoagulant positivity, higher disease damage, and renal biopsy chronicity indices, particularly interstitial fibrosis and tubular atrophy. Only the identification of intrarenal vascular lesions could characterize these patients, thus is it not time to revisit the ISN/RPS classification of LN to include renal vascular lesions of APSN.

Comparison of comorbidities of the Egyptian rheumatoid arthritis patients to the global cohort of the COMORA study: a post-hoc analysis

The aims of this study are to present the results of Egyptian RA patients included in COMORA cohort and compare it to general COMORA cohort, concerning prevalence of comorbidities, and level of application of recommendations related to detection/prevention of comorbidities. Three-hundred eight Egyptian RA patients included in the cross-sectional, observational, multi-center, international study “COMORA”, were compared to the total number of 3612 RA patients. The CRF of COMORA was used in all patients. CRF collects demographic and disease characteristics, comorbidities, risk factors, and compliance with recommendations regarding management of comorbidities. Data were analyzed according to COMORA protocol. Egyptian RA patients were significantly younger, had more active disease, and were more functionally disabled. They showed more frequent use of NSAIDs, methotrexate and steroids and significantly lower use of bDMARDs when compared to non-Egyptians. Egyptian patients had the highest ever HCV prevalence, while depression, hypertension, smoking and dyslipidemia were less prevalent in Egyptians. Prevalence of malignancy risk factors was highly deficient among Egyptians; primarily due to lack of screening. Further, following recommendations for monitoring comorbidities is significantly deficient among Egyptian patients. Egyptian patients had more active disease and more functional impairment than the rest of the COMORA cohort; with lower use of bDMARDs, that is possibly related to the economic situation. Also, there is a clear gap in screening and monitoring comorbidities. Awareness among Egyptian healthcare providers (and possibly similar third-world countries) to detect and manage RA-related comorbidities is required.