Genome-wide association study for systemic lupus erythematosus in an egyptian population.

Systemic lupus erythematosus (SLE) susceptibility has a strong genetic component. Genome-wide association studies (GWAS) across trans-ancestral populations show both common and distinct genetic variants of susceptibility across European and Asian ancestries, while many other ethnic populations remain underexplored. We conducted the first SLE GWAS on Egyptians-an admixed North African/Middle Eastern population-using 537 patients and 883 controls. To identify novel susceptibility loci and replicate previously known loci, we performed imputation-based association analysis with 6,382,276 SNPs while accounting for individual admixture. We validated the association analysis using adaptive permutation tests (n = 109). We identified a novel genome-wide significant locus near IRS1/miR-5702 (Pcorrected = 1.98 × 10-8) and eight novel suggestive loci (Pcorrected < 1.0 × 10-5). We also replicated (Pperm < 0.01) 97 previously known loci with at least one associated nearby SNP, with ITGAM, DEF6-PPARD and IRF5 the top three replicated loci. SNPs correlated (r 2 > 0.8) with lead SNPs from four suggestive loci (ARMC9, DIAPH3, IFLDT1, and ENTPD3) were associated with differential gene expression (3.5 × 10-95 < p < 1.0 × 10-2) across diverse tissues. These loci are involved in cellular proliferation and invasion-pathways prominent in lupus and nephritis. Our study highlights the utility of GWAS in an admixed Egyptian population for delineating new genetic associations and for understanding SLE pathogenesis.

Evaluation of the interaction between anti-apoptotic Bcl-2 protein family mRNA expression and autophagy gene Bcl-1 expression in Egyptian SLE patients.

OBJECTIVES: Autophagy is a complex cellular process that maintains homeostasis in systemic lupus erythematosus. Abnormally high expression of Bcl-2 was observed in B and T lymphocytes in the peripheral blood in SLE patients. These may be responsible for the survival of self-reactive lymphocytes and the development of lupus, and the study aims at evaluating interaction between apoptosis and autophagy in Egyptian lupus patients. METHODS: Sixty patients with SLE were diagnosed by fulfilling the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE and sixty healthy age and sex matched control. All patients were subjected to full medical history and clinical examination. Activity was assessed using SLEDAI-2K score. Gene expression of Beclin-1, Bcl-2-L2, and Bcl-2 was measured. RESULTS: The study revealed that the expression of anti-apoptotic Bcl-2 and Bcl-2-L2 was significantly higher in SLE patients than control subjects, as well as the major apoptotic agent (Beclin-1) mRNA, p = 0.03, < 0.001 and 0.02, respectively. The apoptotic Beclin-1 mRNA was positively correlated with SLE disease severity index, r = 0.25; p = 0.0.4; therefore, our results showed that expression of the Beclin-1 was significantly higher in SLE patients than control (p < 0.02). CONCLUSION: Our results showed that expression of the Beclin 1 were significantly higher in SLE patients than control (p < 0.02).

The Prevalence and Causes of Non-adherence to Immunosuppressive Medications in Patients with Lupus Nephritis Flares.

BACKGROUND: Lupus nephritis is one of the major manifestations of SLE. Poor adherence to medications is an important cause of not achieving treatment targets. METHODS: We assessed patients' adherence to immune-suppressive medications in patients with Lupus nephritis using the Morisky, Green, and Levine (MGL) Adherence Scale. The aim was to study the effect of non-adherence on the occurrence of renal flares. RESULTS: We recruited 104 patients with lupus nephritis. Sixty-six patients had flares of LN. There was a high prevalence of non-adherence to medications (n=68). Patients who were non-adherent to treatment had more renal flares (p= 0.02). Duration of lupus since diagnosis was significantly higher in patients who had renal flares. Using regression analysis, non-adherence to medications was associated with 3.7 higher risk of developing a single renal flare and 4.9 higher risk of developing more than one renal flare. Causes of non-adherence were medications side effects in 43% of patients, financial issues in 31% or forgetfulness in 26%. CONCLUSION: Non-adherence to immunosuppressive medications has a high prevalence in patients with lupus nephritis and is correlated with the number of renal flares.

Late-onset systemic lupus erythematosus: characteristics and outcome in comparison to juvenile- and adult-onset patients-a multicenter retrospective cohort.

INTRODUCTION: The aim of this study was to investigate the characteristics and outcome of systemic lupus erythematosus (SLE) among elderly-onset patients. METHODS: This study included 575 SLE patients managed at Cairo, Alexandria, and Helwan universities from August 2014 to 2018: of whom 49 (8.5%), 420 (73%), and 106 (18.4%) were elderly- (> 50 years), adult- (17-50 years), and juvenile- (≤ 16 years) onset patients, respectively. Cumulative characteristics were recorded. Disease activity at the last visit was investigated through the Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K), whereby lupus low disease activity (LLDA) was defined as a SLEDAI-2K score ≤ 4. The disease outcome was assessed through investigating disease damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)) and the prevalence of mortality. Quantitative and categorical data were compared using Kruskal-Wallis and Mann-Whitney tests, and chi-square (χ2) test, respectively. RESULTS: Late-onset SLE (LSLE) patients demonstrated the lowest prevalence of constitutional and mucocutaneous manifestations (p < 0.001), serositis (p = 0.006), nephritis (p < 0.001), neuropsychiatric involvement (p < 0.001), and hypocomplementinemia (p < 0.001), but showed the highest prevalence of comorbidities and multimorbidity (comorbidities ≥ 2) (p < 0.001), and positive anti-ds DNA antibodies (p < 0.001). Elderly-onset patients demonstrated the lowest SLEDAI-2K and SDI scores, achieved LLDA the most (p < 0.001), and developed any damage (SDI ≥ 1) the least (p < 0.001). The prevalence of mortality was comparable across the three age groups (p = 0.6). CONCLUSIONS: Late-onset SLE patients (8.5%) showed the lowest prevalence of major organ involvement and the highest prevalence of comorbidities, and demonstrated more favorable disease activity and damage indices.Key Points• The disease characteristics and outcome among LSLE patients are characterized by being controversial, with studies from the Middle East being limited. Our cohort constituted of 8.5% elderly-onset SLE patients-who were characterized by the lowest prevalence of major organ involvement and the lowest activity and damage indices-making the disease pattern more favorable in this age group, despite being characterized by the highest prevalence of comorbidities.

Assessment of nutritional status and disease activity level in Systemic Lupus Erythematosus patients at a tertiary care hospital / Evaluación del estado nutricional y el nivel de actividad de la enfermedad en pacientes con lupus eritematoso sistémico en un hospital de atención terciaria

ABSTRACT Introduction: Nutritional status and unhealthy dietary habits may have an influence on Systemic Lupus Erythematosus (SLE) course and activity. Objectives: This work aimed to determine the nutritional status and dietary intake of SLE patients and its relation to disease activity. Material and methods: Sixty-five SLE patients were recruited from Kasr Alainy outpatient clinic from October 2017 to December 2017 in a cross-sectional study. Data were collected using a structured interview questionnaire including inquiry about the socioeconomic status, nutritional status using anthropometric measurements, semi-quantitative food frequency questionnaires (FFQ), and hemoglobin level measurement. Disease activity level was assessed using SLE disease activity index (SLE-DAI). Results: The median age of the enrolled female patients was 30.0 (24.0-37.0), with median disease duration of 3.0 years (1.0-9.0). BMI assessment revealed that more than three quarters of SLE patients were overweight and obese. The semi-quantitative FFQ revealed a decreased consumption of fresh fruit, vegetables, milk and other dairy products and an increased intake of fats and oils. Disease activity (SLE-DAI) correlated with increased BMI (r = 0.299, p = 0.016), body weight (r = 0.276, p = 0.026), and disease duration (r = 0.246, p = 0.049). Conclusions: Inadequate nutrient intake and the high percentage of overweight and obesity among SLE patients with excessive consumption of lipids and low intake of fibers were revealed. Also, disease activity (SLE-DAI) correlated with increased BMI.

RESUMEN Introducción: El estado nutricional y los hábitos alimenticios poco saludables pueden influir en el curso y la actividad del lupus eritematoso sistémico (LES). Objetivos: Este trabajo tuvo como objetivo determinar el estado nutricional y la ingesta dietética de los pacientes con LES y su relación con la actividad de la enfermedad. Material y métodos: Se reclutaron 65 pacientes con LES de la clínica ambulatoria de Kasr Alainy desde octubre de 2017 hasta diciembre de 2017 en un estudio transversal. Los datos se recopilaron mediante un cuestionario de entrevista estructurada que incluía una investigación sobre el estado socioeconómico, el estado nutricional mediante mediciones antropométricas, los cuestionarios de frecuencia de alimentos semicuantitativos (FFQ) y la medición del nivel de hemoglobina. El nivel de actividad de la enfermedad se evaluó utilizando el índice de actividad de la enfermedad del LES (LES-DAI). Resultados: La mediana de edad de las pacientes reclutadas fue de 30,0 (24,0-37,0) años, con una duración media de la enfermedad de 3,0 años (1,0-9,0). La evaluación del índice de masa corporal (IMC) reveló que más de las tres cuartas partes de las pacientes con LES tenían sobrepeso y eran obesas. La FFQ semicuantitativa reveló una disminución del consumo de frutas frescas, verduras, leche y otros productos lácteos, y una mayor ingesta de grasas y aceites. El índice del LES-DAI se correlacionó con un aumento del IMC (r= 0,299; p = 0,016), peso corporal (r = 0,276; p = 0,026) y duración de la enfermedad (r = 0,246; p = 0,049). Conclusiones: Se reveló una ingesta inadecuada de nutrientes y el alto porcentaje de sobrepeso y obesidad entre los pacientes con LES con un consumo excesivo de lípidos y una baja ingesta de fibras. Además, la actividad de la enfermedad (LES-DAI) se correlacionó con un aumento del IMC.