Rania H. EL-kabarity

Higher nitric oxide levels are associated with disease activity in Egyptian rheumatoid arthritis patients

BACKGROUND Oxidative stress generated within inflammatory joints can produce autoimmune phenomena and joint destruction. Radical species with oxidative activity, including reactive nitrogen species, represent mediators of inflammation and cartilage damage. OBJECTIVES To assess serum nitric oxide as a marker of oxidative stress in Egyptian patients with rheumatoid arthritis and its relation to disease activity. METHODS 80 patients with rheumatoid arthritis were divided into 2 groups, according to the DAS-28 score: Group I: 42 patients with disease activity, and Group II: 38 patients with no disease activity. Forty age- and sex-matched individuals were included as control group (Group III). Routine laboratory investigations were done, and nitric oxide was measured using Elisa. Hand plain radiographies were done for radiological status scoring using the Sharp method. RESULTS A comparison between nitric oxide in all three groups showed a highly significant difference (p < 0.001), significantly higher levels were obtained among rheumatoid arthritis patients in comparison to controls, and higher levels were obtained in patients with active disease (mean±SD 82.38±20.46) in comparison to patients without active disease (35.53±7.15). Nitric oxide in Group I showed a significant positive correlation with morning stiffness (r=0.45), arthritis (r=0.43), platelet count (r=0.46), erythrocyte sedimentation rate (r=0.83), C-reactive protein (r=0.76) and Disease Activity Score (r=0.85). Nitric oxide showed a significant positive correlation (r=0.43) with hand radiographies (Sharp score) in Group I. CONCLUSION There are increased levels of nitric oxide in the serum of patients with rheumatoid arthritis. Nitric oxide correlates significantly with disease activity, inflammatory markers and radiological joint status.

Ischemic heart disease and rheumatoid arthritis: Do inflammatory cytokines have a role?

Background The increase in Rheumatoid arthritis (RA) associated mortality is predominantly due to accelerated coronary artery and cerebrovascular atherosclerosis with increased risk of ischemic heart disease about 50% in RA patients compared to controls. Objective To study the pathogenesis of ischemic heart disease in RA, role of inflammatory cytokine interplay, disease activity and rheumatoid factor positivity. Methods Eighty RA patients and 44 healthy controls were included. All subjects were younger than 45 years for females and 55 years for males with exclusion of all traditional risk factors for atherosclerosis. Interleukin (IL) 1, 6 and 18 were assessed in all subjects. RA patients fulfilled ACR/EULAR 2010 criteria and were subjected to Dobutaminestress‐echocardiography, diseases activity assessed by DAS‐28, X‐ray hands for Larsen score and function assessment by HAQ. Results RA patients had significantly higher serum IL 1, 6 and 18 than controls (p = 0.00 in all). Thirty four (42.5%) patients had hypertensive reaction on Dobutamine‐stress‐echocardiography, four of them had ischemic change, and 46 (57.5%) had normal reaction. All patients with hypertensive reaction had positive RF (p = 0.00), 10 had DAS‐28 > 5.1, 20 had DAS‐28 from 3.2 to5.1 and 4 were in remission (p = 0.001). CRP was higher in patients with hypertensive reaction (p = 0.003) while serum levels of IL1, 6 and 18 showed no significant difference. In all patients, serum levels of IL1, 6 and 18 showed significant positive correlation with VAS, HAQ and DAS‐28 (p < 0.001 in all). Only IL18 showed significant positive correlation with X‐ray score in all patients. Conclusion Disease activity and RF positivity play an important risk factor for ischemic heart disease in RA. Serum levels of IL1, 6 and 18 did not help much in detecting patients at risk of ischemic heart disease. Better control of RA disease activity with early remission helps in preventing cardiac complications. More studies on larger number of patients are needed for better understanding of mechanism of ischemic heart disease in RA. HighlightsRheumatoid arthritis.Ischemic heart disease.Interleukins‐1beta, 6 and 18.

Vitamin D Deficiency in Egyptian Systemic Lupus Erythematosus Patients: How Prevalent and Does It Impact Disease Activity?

BACKGROUND The emerging role of vitamin D in immunology and autoimmune disorders has been a worldwide interest in the last decade. Systemic lupus erythematosus (SLE) patients are particularly at a delicate position predisposing them to suffer from vitamin D deficiency due to the multiple risk factors accompanying the disease. Whether vitamin D deficiency is also involved as a risk factor for developing SLE and affecting its course is a considerable concern. OBJECTIVES The objective of this study was to estimate the prevalence of vitamin D deficiency in SLE patients and its relation to disease. MATERIALS AND METHODS In our observational cross-sectional study, serum levels of vitamin D [25(OH)D] in 60 SLE patients and 30 age- and sex-matched healthy controls were assessed and estimated for deficiency and insufficiency at 10 and 30 ng/mL, respectively. Disease activity was evaluated by SLE disease activity index (SLEDAI), irreversible organ damage by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI), and severity by Severity of Disease Index. Fatigue was measured by visual analog scale. RESULTS Significantly lower levels of 25(OH)D were found in SLE patients (17.6 ± 6.9 ng/mL) in comparison to controls (79.0 ± 28.7 ng/mL), with a statistically high significant difference (t = −11.2, P < 0.001). High prevalence of vitamin D insufficiency and deficiency was detected as 73.3% and 23.3%, respectively. Vitamin D had a highly significant negative correlation with SLEDAI (r = −0.495, P < 0.001), SLICC (r = −0.431, P < 0.05), and fatigue (r = −0.436, P < 0.05). CONCLUSION Vitamin D deficiency and insufficiency were found to be prevalent in SLE patients in our study and related to disease activity and fatigue. If needed, routine screening and consequent repletion of vitamin D are recommended in SLE patients. Restoring adequate vitamin D levels in SLE patients should be more explored as a potential yet simple measure to their usual management to improve their condition.

FRI0417 Vitamin D Deficiency Prevalence in Systemic Lupus Erythematous; Regardless A Cause or a Consequence does it Impact Disease Course, Activity or Severity?

Background Emerging role of vitamin D in immunology and autoimmune disorders has been a worldwide interest in the last decade. Systemic lupus erythematosus (SLE) patients are particularly at a delicate position predisposing them to suffer from vitamin D deficiency due to the multiple risk factors accompanying the disease. Whether vitamin D deficiency is also involved as a risk factor for developing SLE and affecting its course is a considerable concern. Objectives To estimate prevalence of vitamin D deficiency in SLE and its relation to disease activity and severity. Methods In our observational cross-sectional study, serum levels of vitamin D from 60 SLE patients and 30 age & sex matched healthy controls (HC) were assessed and estimated for deficiency or insufficiency at 10 and 30ng/ml respectively. Disease activity was evaluated by SLEDAI, irreversible organ damage by SLICC/ACR index and severity by Lupus SDI. Fatigue was measured by visual analogue scale (VAS). Results Significantly lower levels of 25(OH)D were found in SLE patients (17.6±6.9 ng/ml) in comparison to controls (79.0±28.7 ng/ml)with statistically high significant difference (t=-11.2, p<0.001).High prevalence of vitamin D insufficiency and deficiency was detected 73.3% & 23.3% respectively. Vitamin D had a highly significant negative correlation with SLEDAI (r =-0.495, p<0.001), see figure 1a, SLICC (r =- 0.431, p<0.05) as well as fatigue (r =- 0.436, p<0.05), see figure 1b. After standardization of all clinical variants, regression analysis study showed that there is significantly inverse correlated between vit D and VAS (standardized regression coefficient β=-0.443, p=0.024) and a highly significant correlation between vit D and SLEDAI score (β=-0.940, p=0.012). Figure 1. a. Correlation between serum vitamin D and SLEDAI. b. Correlation between serum vitamin D and VAS of fatigue. Conclusions Vitamin D deficiency & insufficiency were found to be prevalent in SLE patients in our study and related to disease activity & fatigue. Routine screening and consequent repletion of vitamin D if needed is recommended in SLE. Restoring adequate vitamin D level in SLE should be more explored as a potential and simple yet valuable measure to be added to their usual management to alleviate their condition. References Kamen DL, Cooper GS, Bouali H, Shaftman SR, Hollis BW, Gilkeson GS. Vitamin D deficiency in systemic lupus erythematosus. Autoimmun Rev 2006; 5: 114–117. Ruiz-Irastorza G, Egurbide MV, Olivares N, Martinez-Berriotxoa A, Aguirre C. Vitamin D deficiency in systemic lupus erythematosus: prevalence, predictors and clinical consequences. Rheumatology (Oxford) 2008;47:920–3. Fragoso TS, Dantas AT, Marques CD, Rocha Junior LF, Melo JH, Costa AJ, Duarte AL. 25-Hydroxyivitamin D3 levels in patients with systemic lupus erythematosus and its association with clinical parameters and laboratory tests. Rev Bras Reumatol. 2012 Jan-Feb;52(1):60-5 Disclosure of Interest None declared

Serum vitamin D and peripheral T-regulatory cells in systemic lupus erythematosus and their relation with disease activity

Background Systemic lupus erythematosus (SLE) patients have a decreased number of T-regulatory cells (Tregs) in peripheral blood. Vitamin D deficiency is prevalent in SLE. Immunomodulatory effects of vitamin D include the expansion of Tregs. Objectives The aim of this study was to assess the percentage of Tregs and vitamin D level in SLE and their relation with disease activity. Patients and Methods A total of 40 SLE patients underwent evaluation for disease activity using the SLE disease activity index and were tested for the percentage of peripheral Tregs using anti-CD4, anti-CD25, and anti-FOXP3 monoclonal antibodies. Vitamin D was assessed using a commercially available 25-OH VitD-EIA kit. The study also included 40 healthy individuals who served as controls. Results SLE patients had lower levels of vitamin D (22.3 ± 7.53) and Treg% (1.95 ± 0.18) in comparison with controls. Patients with active disease had significantly lower levels of vitamin D. However, there was no significant difference between patients with and those without disease activity as regards Tregs. Correlation between vitamin D and various disease parameters showed negative correlation between vitamin D and each of disease activity, creatinine, and urinary protein ( P 4 ( P P < 0.05). No correlation was detected between Tregs% and vitamin D. Conclusion There are decreased levels of vitamin D and Treg% in SLE. Lower levels of vitamin D correlate with disease activity; yet, no correlation between serum vitamin D and Treg% was detected.

THU0092 CD4+CD25+FoxP3+ T Regulatory Cells in Rheumatoid Arthritis: Decreased or Increased but not Able to Fight Back Inflammation? is it a Question of Number or Balance with their Counteracting FoxP3- Population?

Background Despite the presence of an increase in immunoregulatory cells in rheumatoid arthritis (RA), chronic inflammation persists and activity recurs. This finding has been intriguing rheumatologists and immunologists trying to justify the presence of activity daring this quarterback of cells usually aiming to fight inflammatory process. Namely the forkhead box P3 (FoxP3) transcription factor, essential for T regulatory cells (T regs) development and function is now considered their most specific marker denoting FoxP3+ cells as suppressors whereas FoxP3- effectors. Objectives To clarify the subsets distribution of peripheral blood (PB) CD4+CD25+ T regulatory cells (T regs) according to FoxP3 expression in RA (both in remission & activity) for a better understanding of RA pathogenesis highlighting future therapeutic targets. Methods In our observational cross-sectional study PB T regs from 40 RA patients & 20 age and sex matched healthy controls (HC) were characterized and quantified by flow cytometry. Disease activity was evaluated by DAS28. Patients were divided into 2 equal groups: active RA group (ARA) & remission RA group (RRA). All patients were on methotrexate MTX and folic acid. Results A significantly higher T regs subsets numbers were found on comparing RRA, ARA patients & HC as shown in table 1 Conclusions CD4+CD25+FoxP3+ & CD4+CD25+FoxP3- are both increased in RA but it is their balance that is more important; the abundance of Foxp3- cells gave the effector function the upper hand over the suppressive function represented in Foxp3+ cells. This imbalance is related to the presence of RA & to its activity. Restoring this imbalance by future targeting therapeutics might be of great benefit in RA patients. References Beyer M & Schultze JL: Regulatory T cells in cancer. Blood. 2006; 108:804–811. Wan YY & Flavell RA: Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression. Nature. 2007;445:766–770. Han GM, O’Neil-Andersen NJ, Zurier RB & Lawrence DA:CD4+CD25high T cell numbers are enriched in the peripheral blood of patients with rheumatoid arthritis. CellImmunol. 2008; 253(1-2):92-101. Disclosure of Interest None Declared