Egyptian Systemic Lupus Erythematosus Patients Research Articles

Autoimmune Regulator Gene Polymorphisms in Egyptian Systemic Lupus Erythematosus Patients: Preliminary Results.

Background Systemic lupus erythematosus (SLE) is a systemic autoimmune disease. The autoimmune regulator (AIRE) is a master regulator of self-tolerance development. AIRE mutations lead to the development of autoimmune polyglandular syndrome type 1 while AIRE polymorphisms have been linked to organ-specific autoimmunity. The study is aimed at addressing the association between AIRE polymorphisms, rs2075876 (G > A) and rs760426 (A > G), and SLE susceptibility and expression in Egyptian patients. Methods Ninety-nine patients were included. One hundred and ten, and 123 control subjects were genotyped for rs2075876 and rs760426, respectively. Lupus severity was assessed using the Lupus Severity of Disease Index and Lupus Severity Index (LSI). Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) damage index was considered. Genotyping was done using StepOne Real-Time PCR. Results. AIRE rs760426 GG was more frequent in the patients under the genotype level (14.1% vs. 4.9%, p = 0.032) and recessive model (14.1% vs. 4.9%, p = 0.017, OR = 3.2 (1.2-8.7)). Musculoskeletal involvement and nephritis were associated with AIRE rs2075876 under the dominant (97.9% vs. 80.8%, p = 0.009, OR = 11 (1.3-89.2)) and recessive models (100% vs. 69.3%, p = 0.032), respectively; and both were linked to AIRE rs2075876 at the allelic level: 98.3% vs. 85%, p = 0.005, OR = 10.1 (1.3-76.6) and 82.8% vs. 68.6, p = 0.041, OR = 2.2 (1-4.7), respectively. Patients with AIRE rs2075876 A alleles had a higher damage index ( 1 ± 1.3 vs. 0.6 ± 1.1, p = 0.045) while the LSI was greater in patients with AIRE rs2075876 (8.5 ± 0.5 vs. 7.8 ± 1.3, p = 0.002) and rs760426 (8.6 ± 11 vs. 7.8 ± 1.2, p = 0.031) under the recessive models. Conclusion. AIRE rs760426 could share in SLE susceptibility while AIRE rs2075876 could influence the disease expression and burden in Egyptian patients.

Challenges of Egyptian patients with systemic lupus erythematosus during the COVID-19 pandemic.

ObjectivesThe coronavirus disease 2019 (COVID-19) pandemic in Egypt is part of the worldwide COVID-19 pandemic that has contributed to substantial deterioration of healthcare systems. The aim of this study was to assess the challenges faced by Egyptian systemic lupus erythematosus (SLE) patients during the COVID-19 pandemic.Material and methodsThis questionnaire-based study was carried out on 200 patients with SLE from Egypt. The questionnaire provided covered socioeconomic status, lupus disease data, information about COVID-19 infection, and medical and family history of COVID-19 infection.ResultsThe mean age of the participants was 30.1 ±8.4 years. 140/200 (70%) of the participants reported difficulty in obtaining medications during the COVID-19 pandemic, particularly antimalarials (60%). The lupus disease condition became worse because of the drug shortage in half of the participants. Wearing protective masks (74%) and using disinfectants of the hands several times per day (67%) were the most reported used measures. Forty patients (20%) had to stop or reduce taking nonsteroidal anti-inflammatory drugs while 10 patients (5%) had to start taking antimalarials as a prophylaxis against COVID-19 infection. Among those who needed hospitalization, the main cause was lupus activity, and most of them (71%) experienced difficulty in hospital admission. Thirty-two patients (16%) had confirmed COVID-19 infection. About half of them had lupus flare and had to change the medications used for treatment of lupus.ConclusionsThe current COVID-19 pandemic has a negative impact on the healthcare provided to SLE patients in Egypt. Patients with SLE faced a shortage of their medications, especially antimalarials, and difficulty in hospital admission.

Genetic polymorphisms of IL-27 and risk of systemic lupus erythematosus disease in the Egyptian population.

Cytokine polymorphisms have been associated with systemic lupus erythematosus (SLE) pathogenicity. Interleukin 27 (IL-27) is an important one of pro-/anti-inflammatory cytokine. It has been reported in various Th1/Th17-mediated inflammatory disorders, and even in Th2-complexed diseases, such as SLE. In our preliminary study, the aim was to investigate the potential roles of single nucleotide polymorphism (SNP) -964A/G (rs153109) and + 2905T/G (rs17855750) in an IL-27p28 gene on susceptibility to SLE. The 112 Egyptian SLE patients against 101 healthy persons were enrolled in this work. The polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) is used for genotyping IL-27 SNPs. No significant variations were found between patients and control in the genotype and allele frequencies of IL-27p28 (-964A/G). SLE patients have a significant increase in the frequency of IL-27p28 (+ 2905T/G) TG genotype (P < 0.01) and G allele (P < 0.01) compared to controls. Complete disappearance of GG genotype was demonstrated in both groups. G allele might have considered a disease risk factor with odd ration (OR) = 9.184. From four possible haplotypes, the frequency of AT haplotype elevated in both examined groups. This was the first study on the Egyptian population for studying the relation between IL-27 SNPs and SLE. Our preliminary study indicated that both TG genotype and G allele of IL-27p28 (+ 2905T/G) could consider risk factors for SLE. Key Points • This article provides an information about the relation between systemic lupus erythematosus and interleukin-27 cytokine by detection single nucleotide polymorphism.

POS1265 CHALLENGES OF EGYPTIAN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS DURING COVID-19 PANDEMIC

Background:Coronavirus disease 2019 (COVID-19) pandemic in Egypt is part of worldwide COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)[1]. The current COVID-19 pandemic has contributed to substantial deterioration to healthcare systems worldwide [2].Systemic lupus erythematosus (SLE) patients may have several barriers as medications access during the pandemic.Objectives:The aim of this study was to assess the tremendous challenges faced by the Egyptian SLE patients during COVID-19 pandemic either in the drug shortage, hospitalization or COVID-19 infection through a questionnaire-based study.Methods:This questionnaire-based study was carried out on 200 patients with SLE from Egypt. The questionnaire provided covered socioeconomic status, lupus disease data, knowledge about COVID-19 infection and medical and family history of COVID-19 infection.Results:The mean age of the participants was 30.1 years (with SD 8.4). Among the participants,180 (90 %) were females and 172 (86%) were from urban areas. Corticosteroids and mycophenolate mofetil and antimalarials were the most used medications (87%,87% and 70 % respectively). 140/200 (70 %) of the participants reported difficulty in obtaining medications during COVID-19 pandemic particularly antimalarials (60%). Lupus disease activity was affected by the drug shortage in half of the participants. Twenty-eight (14%) patients lost their jobs while 26 patients (13%) reported that their work was severely impacted by the crisis. Among the precautions taken for prophylaxis against infection wearing protective masks (74%) and using disinfectants of the hands several times per day (67%) were the most reported measures. Forty patients (20%) had to stop or reduce taking NSAIDs to guard against COVID-19 infection while 10 patients (5%) had to start taking antimalarials as a prophylaxis. Among 34 patients (17%) who needed hospitalization,26 (76%) were mainly due to lupus activity and 24 (71%) of them found difficulty on hospital admission because of COVID-19 pandemics. About 40 % of the participants reported that they had at least one close relative had confirmed COVID-19 infection. In addition, thirty-two patients (16%) had confirmed COVID-19 infection. Most of them became clinically free after treatment. However, about half of them had lupus flare and had to change the medications used for treatment of lupus.Figure 1 shows the differences between males and females in response to the questionnaire. 58.6% of females versus 20 % of males would use telemedicine for remote contact with the rheumatologist. Most of females were more keen than males to wear the masks (76.7% versus 50 % respectively).Conclusion:The current COVID-19 pandemic has negative impact on the healthcare provided to SLE patients in Egypt. Patients with SLE faced shortage their medications especially antimalarials.

Association of interleukin-36α gene expression in Egyptian patients with systemic lupus erythematosus with organ involvement and disease activity

Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease characterized by a wide spectrum of clinical manifestations with varying severity. The dysregulation of cytokines contributes strongly to disease pathogenesis. Recently, it has been shown that the imbalanced antagonist/agonist profile of interleukin (IL)-36 cytokines, might play a role in autoimmune disorders. Our aim is to investigate mRNA expression of Interleukin-36α (IL-36α) in the peripheral blood of Egyptian systemic lupus erythematosus (SLE) patients and its association with disease activity and organs involvement. We assessed the relative expression of IL-36α mRNA by real time polymerase chain reaction and the comparative CT method on the peripheral blood of 49 SLE patients, and 40 healthy controls. Patients were subjected to thorough history and clinical examination, in addition to routine hematological, biochemical, and serological studies. Disease activity was evaluated using the SLE Disease Activity Index (SLEDAI). The relative expression of IL-36α mRNA was significantly higher in SLE patients compared to healthy controls (4.3±2.9 vs 1, respectively, P<0.0001). Fold change of IL-36α expression was significantly increased in patients with moderate and high disease activity (SLEDAI>5) than patients with mild disease activity (SLEDAI≤5) (4.3±1.2 vs 2.7±2.0, respectively, P=0.006) and positively correlated with SLEDAI (r=0.505, P=0.001). Regarding major organ involvement, the mean±SD expression of IL-36α in patients with arthritis and mucocutaneous involvement was significantly higher compared to those without organ involvement (4.2±1.5 vs 2.8±1.8, P=0.039 and 4.1±1.4 vs 2.8±2.1, P=0.041, respectively). In conclusion, the IL-36α is significantly more expressed in SLE patients compared to healthy controls and correlated with SLE disease activity and arthritis. IL-36α expression could be a useful biomarker for SLE disease activity in Egyptian patients with SLE.

Impact and associations of lymphopenia in a cohort of Egyptian systemic lupus erythematosus patients: Potential link to complement (C3) and corticosteroids

Aim of the workTo investigate the relation between lymphopenia and clinical disease activity, disease associated end organ damage, laboratory markers and medications received in systemic lupus erythematosus (SLE) patients. Another objective was to investigate the prognostic value of lymphopenia. Patients and methodsThe medical records of 698 SLE patients under follow-up at the Rheumatology clinics of Cairo and KafrElsheikh University hospitals were revised. Demograghic and laboratory data, SLE disease activity index (SLEDAI), damage index and drug history were assessed. ResultsMean age of 28.4 ± 8.8 years (12–60 years), they were 640 females and 58 males (F:M 11:1) and a disease duration of 6.2 ± 4.7 (0.1–31 years). The study included 674 adults and 24 juvenile cases. 280 (40%) had lymphopenia. Patients with lymphopenia had significantly consumed complement 3 (C3) (p < 0.001), C4 (p = 0.002) and anticardiolipin IgG (p = 0.05). Patients with lymphopenia had a significantly higher incidence of infections (p < 0.001), antiphospholipid antibodies (p = 0.014), frequent intake of cyclophosphamide (p = 0.001), pulse steroid therapy (p < 0.001) and other drugs (p = 0.009) including IVIG and plasmapheresis. Univariate regression model revealed the predictive potential of consumed C3, anticardiolipin IgG, cyclophosphamide, pulse steroid therapy, steroids > 40 mg/day, infections, antiphospholipids for associated lymphopenia. On multivariate analysis only consumed C3 (p = 0.008) and pulse steroid therapy (p = 0.036) remained as independent risk factors for lymphopenia. ConclusionLymphopenia may be more than a hematological finding in SLE patients that was found to be associated with complement consumption, high steroid doses and cyclophosphamide administration, infections and antiphospholipids. The key independent risk factors for lymphopenia are pulse steroid and C3.

Mortality in a cohort of Egyptian systemic lupus erythematosus patients: retrospective two-center study

BackgroundSystemic lupus erythematosus is a debilitating autoimmune disease with major contribution to the worldwide morbidity and mortality. This study aimed to investigate the causes of mortality in systemic lupus erythematosus (SLE) patients and the relation between clinical activity, disease-associated end-organ damage, laboratory markers and mortality.ResultsAmong the 771 patients who were successfully followed up, 34 patients (4.4%) died. The leading causes of death were infectious causes (35.29%), cardiopulmonary causes (26.48%), renal causes (14.7%), unknown causes (14.7%), neuropsychiatric causes (5.88%), and lastly gastrointestinal causes (2.94%). Subjects who died had lower complement 3 level, more anemia, lymphopenia, neutropenia, leukocytosis, thrombocytopenia, decreased glomerular filtration rate, higher incidence of infection, end-stage renal disease, and cardiopulmonary complications. Higher glucocorticoid dosage with more immunosuppressant (mofetil and cyclophosphamide) treatment was observed in patients who died. SLE disease Activity Index and Systemic Lupus International Collaborating Clinics damage index were both significantly higher in deceased persons. Multivariable hazards regression analysis revealed that lymphopenia (p = 0.017), decreased glomerular filtration rate < 50% (p = 0.002) with end-stage renal disease (p = 0.001), and high steroid daily use of > 40 mg (p = 0.016) were independent risk factors for the mortality of SLE patients.ConclusionInfections and cardiopulmonary complications are the leading causes of death in two centers caring for Egyptian SLE patients. Lymphopenia, end-stage renal failure, and high steroid daily use were associated with poor outcomes.

Measurement of serum interferon alpha in Egyptian patients with systemic lupus erythematosus and evaluation of its effect on disease activity: a case-control study.

Much evidence highlighted the role of interferon alpha (IFN-α) in systemic lupus erythematosus (SLE) and suggested its possible role in assessing disease activity. We measured serum IFN-α in Egyptian SLE patients in order to determine a cutoff value that can be used to distinguish patients from healthy controls and explored its clinical value in monitoring disease activity and different aspects of the disease, in particular lupus nephritis. This cross-sectional, case-control study was conducted on 59 SLE patients and 30 healthy controls. Serum IFN-α was measured in all participants using sensitive enzyme-linked immunosorbent assay (ELISA). SLE patients underwent assessment of disease activity using the SLE disease activity index-2000 (SLEDAI-2K) as well as an evaluation of proteinuria, complement C3 and C4, and serology. Patients with evidence of renal involvement underwent renal biopsy. The median serum IFN-α was 81.8 pg/mL (interquartile range [IQR] 63.4:102.4), which was significantly higher than in healthy controls (median 10.3 pg/mL [IQR 7.3:11.6]) (p<0.001). At serum level of 14.7 pg/mL, IFN-α has high sensitivity and specificity to discriminate SLE patients from controls, with high positive and negative predictive values. Serum IFN-α was not associated with markers of disease activity, clinical features and anti-double stranded DNA. Furthermore, it was not associated with markers of renal activity, including proteinuria, C3 and C4 complement factors and histopathology renal classes. Despite elevated levels of serum IFN-α in SLE patients, it is not possible to use it as a biomarker for disease activity.

The Arabic LupusPRO: A Cross-Cultural Validation of a Disease-Specific Patient-Reported Outcome Tool for Quality of Life in Lupus Patients.

To translate and cross-culturally adapt the Arabic version of LupusPRO v.1.8 and to test its reliability and validity. LupusPRO was translated into the Arabic language following a standard procedure with forward-backward translation and was tested in patients with systemic lupus erythematosus (SLE) before use. The Arabic version was administered to 107 Egyptian SLE patients, along with a validated Arabic version of RAND 36-Item Health Survey 1.0 (SF-36). The internal consistency and test-retest reliability were determined. Validity was assessed by correlating LupusPRO scores with SF-36, Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). The conceptual framework of the Arabic LupusPRO was evaluated using confirmatory factor analysis (CFA). Among the 107 SLE patients, 95% were women with a median (range) age of 32 (18-55) years, median (range) SELENA-SLEDAI of 6 (0-23) and median (range) SDI of 0 (0-6). The Cronbach's alpha for the Arabic LupusPRO ranged from 0.71 to 0.98, except for the social support domain (0.65). Test-retest reliability ranged from 0.95 to 0.99. Convergent validity with corresponding domains of SF 36 was satisfactory. For criterion validity, there was a weak but significant correlation between several LupusPRO domains with SELENA-SLEDAI. CFA showed a good model fit. The Arabic version of LupusPRO v1.8 is a reliable and valid tool for measuring quality of life among Arabic speaking SLE patients.

Gene XRCC1Arg399Gln polymorphism and its genotype variations: clinical associations in Egyptian systemic lupus erythematosus patients

BackgroundImpaired deoxyribonucleic acid (DNA) repair may induce an autoimmune response in susceptible individuals. The association between DNA repair gene XRCC1 Arg399Gln gene polymorphism and susceptibility of systemic lupus erythematosus (SLE) is controversial. This study aimed to detect the association of XRCC1 Arg399Gln gene polymorphism with SLE and its clinical manifestations in the Egyptian population.ResultsA significant association was found between weight loss and genotype GG (P = 0.048); however, genotype AG was significantly associated with high serum creatinine and low C3 level (P = 0.039, P = 0.009, respectively). On the other hand, there was no significant difference between patients and controls regarding genotype and allele frequency.ConclusionsAn association was found between weight loss, high serum creatinine, and low C3 level and genotypes of XRCC1 Arg 399 Gln gene polymorphism.

Evaluation of autophagy-related genes in Egyptian systemic lupus erythematosus patients.

Disturbances in autophagy are known to be implicated in autoimmune disorders. Many studies have connected polymorphisms in autophagy-related gene 5 (ATG-5) to systemic lupus erythematosus (SLE). Our aim was the determination of the expression level of ATG-5, Beclin-1 and microtubule-associated protein-light chain 3 (LC-3) in Egyptian SLE patients to investigate the impact of disturbances in autophagy genes on the incidence and progression of the disease. Also, we investigated the incidence of single nucleotide polymorphism (SNP) rs573775 in ATG-5 gene among Egyptian SLE patients. Our results showed that the mean levels of Beclin-1, LC-3 and interleukin (IL)-10 transcripts were significantly higher in SLE patients compared to healthy controls. The previous transcripts were positively correlated with SLE Disease Activity Index (SLEDAI). Beclin-1 and LC-3 transcripts were negatively correlated to complement component 3 (C3) levels. Only LC-3 transcripts were negatively correlated to complement component 4 (C4). The rs573775 SNP of ATG-5 with the variant allele was significantly associated with disease susceptibility, conferring a higher risk of SLE development. This variant allele was more prevalent in patients below 30years, patients with anemia and in patients with anti-double-stranded DNA (dsDNA), confirming the essential role of ATG-5 polymorphism in the susceptibility of Egyptian patients to SLE.

MicroRNA-126 and 146a as potential biomarkers in systemic lupus erythematosus patients with secondary antiphospholipid syndrome

BackgroundMicroRNAs (miRs) are noncoding gene regulators that may have a role as diagnostic or prognostic biomarkers in systemic lupus erythematosus (SLE) and its complications. SLE is an autoimmune disease that may be associated with secondary antiphospholipid syndrome (APS). Aim of the workTo evaluate the plasma levels of both miR-146a and miR-126 as well as serum alpha interferon (α IFN) in Egyptian SLE patients with and without secondary APS and to investigate their potential role in disease pathogenesis and their utility as biomarkers for APS. Patients and methods88 SLE patients including 30 cases with secondary APS and 40 matched healthy individuals were enrolled in this study. SLE disease activity index (SLEDAI) was assessed. The plasma levels of miR-146a and miR-126 were determined by Realtime polymerase chain reaction (PCR) in all participants. ResultsThe mean age of the patients was 31.3 ± 9.6 years with disease duration 1–17 years. Plasma miR-146a was significantly lower and miR-126 significantly higher in SLE compared to controls. MiR126 was also higher in secondary APS patients compared to patients without. Serum IFN-α ws significantly higher in patients (71.2 ± 19.7 pg/ml) compared to control (43.2 ± 9.7 pg/ml) (p < 0.001). MiR-126 at a cut off of 2.66 can discriminate between SLE patients with and without secondary APS with a sensitivity of 76.67% and specificity of 81.01% ((95% CI 0.685–0.902, P < 0.001). ConclusionCirculating miR-126 could be a potential noninvasive biomarker in SLE associated with secondary APS. Further studies are needed in view of the limited data on the expressions of microRNA in APS.

Neutrophil/lymphocyte and platelet/lymphocyte ratios are useful predictors comparable to serum IL6 for disease activity and damage in naive and relapsing patients with lupus nephritis

Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have become recently useful as predictive and prognostic tools in patients with various medical conditions. Aim of the workTo evaluate NLR and PLR in systemic lupus erythematosus (SLE) and their relation to disease clinical characteristics, nephritis, disease activity and damage. Patients and methodThe study involved 110 Egyptian SLE patients; 80 with lupus nephritis (naive and relapsing) and 30 without as well as 50 matched control. Patients were subjected to full clinical examination, SLE disease activity index (SLEDAI) scoring, and damage using Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI). Laboratory and immunology profiles included the complete blood count (CBC) with differential white blood cell counts and estimation of both NLR and PLR, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), protein/creatinine ratio, anti-nuclear antibody (ANA), anti-double stranded deoxyribonucleic acid (anti-dsDNA), serum complements and interleukin-6 (IL-6) levels. ResultBoth NLR and PLR were significantly higher in SLE patients (4.8 ± 1.4 and 281.7 ± 66.7 respectively) compared to controls (3.8 ± 2 and 138.2 ± 50.4). Both ratios were significantly elevated in patients with active lupus nephritis (at presentation or as a flare) and were comparable between naive and relapsing lupus nephritis patients. In lupus nephritis patients, NLR and PLR significantly correlated with proteinuria, ESR, hypocomplementemia, IL6, SLEDAI and SLICC-DI. The best NLR cut-off value to predict nephritis activity was 5.65, whereas the best PLR cut-off value was 316.5. ConclusionNLR and PLR appear to be potentially useful cheap parameters of activity, relapse and severity in SLE patients with nephritis.

SEROLOGY OF THE SYSTEMIC LUPUS ERYTHEMATOSUS IN EGYPTIAN PATIENTS

Systemic lupus erythematosus (SLE) is a prototypic multisystem autoimmune disease with a vast spectrum of clinical presentations including almost all body organs and tissues. The incidence of lupus has tripled in the last 40 years, mainly due to the improved diagnosis. For more than 60 years the presence of autoantibodies in patients with SLE has been known. A great effort is being made for understanding the diagnostic, pathogenic and prognostic meaning of these autoantibodies. The study demonstrated the significance of autoantibodies test in Egyptian SLE patients. The results showed that 93.3% of patients have positive ANA test, 90% have positive anti-dsDNA. Anti-Sm antibodies were in 40% and 49.3% of patients have positive anti-nucleosome antibody test. Also, 30.6% of patients deve-loped a positive anti-histone test & 26% have positive anti-ribosomal test. Anti-phospholipids antibodies were found in 44.6% of patients. Levels of C3 & C4 (0.552±0.43 & 0.125±0.12, respectively) were lower than that of control group (1.2±0.35 & 0.42±0.54 for C3 & C4, respectively).

Risk factors for cataracts in a cohort of Egyptian systemic lupus erythematosus patients

Aim of the workThis study was undertaken to evaluate cataract risk factors in Egyptian systemic lupus erythematosus (SLE) patients. Patients and methodsA cohort of 150 consecutive adult SLE patients was included. None of the patients was diabetic or had cataract before steroids treatment for SLE. Detailed medical and ophthalmological histories were taken. Thorough clinical examination was performed with assessment of SLE disease activity index (SLEDAI) and systemic lupus international collaborating clinics damage index (SLICC DI), along with routine blood tests. Slit lamp examination was done to assess the anterior segment of the eye especially the lens to detect the type and degree of cataract. Results150 SLE patients were studied with a mean age of 37.16 ± 11 years; 129 females and 21 males and a mean disease duration of 11 ± 5.7 years. Their mean SLEDAI was 4.1 ± 3.78 and SLICC/DI 2.1 ± 1.3. The frequency of cataract was 18% (n = 27); 22.2% of them were cortical and 77.8% were posterior subcapsular with mild-moderate degree. Glaucoma was present in only 2%. A significant increase in age, disease duration, age at onset, SLICC/DI, cumulative steroid dose and hydroxychloroquine (HCQ) dose was found in those with cataract compared to non-cataract patients (p < 0.05). The age, age at onset, disease duration, SLICC/DI and cumulative steroid dose were significant independent factors increasing the probability of cataract occurrence among SLE patients (p < 0.01). ConclusionAlthough corticosteroids are prescribed to control SLE symptoms, these results highlight potential risks associated with their use, especially cataracts, which require careful and routine ophthalmologic examination and follow up.

Secondary amenorrhea in a cohort of Egyptian systemic lupus erythematosus patients

Aim of the workTo detect the frequency of secondary amenorrhea in a cohort of Egyptian systemic lupus erythematosus (SLE) patients and to identify potentially related key-players. Patients and methodsThe medical records of 140 adult SLE patients above 18 and less than 40 years were revised regarding clinical characteristics, immunological features and medications received. The SLE disease activity index (SLEDAI) and damage index (SLICC-DI) were recorded. Patients were divided into two groups: patients who developed secondary amenorrhea and those having normal menstrual cycles. ResultsThe mean age of the patients was 26.8 ± 5.7 years, the median disease duration was 3.5 years. The patients had renal involvement in 69.3%, neuropsychiatric in 23.6% and cardiac in 37.9%. Cyclophosphamide (CYC) was received by 52.1% and steroids by 139 patients. Secondary amenorrhea was found in 44 patients (31.4%); 36 (81.8%) of them were ≤32 years old. Patients with secondary amenorrhea had a higher frequency of positive anti-double stranded deoxyribonucleic acid (ds-DNA) antibodies (75% vs 50%; p = 0.04) and a shorter disease duration (median 2 years vs 4.5 years; p = 0.005). Lupus nephritis, renal failure, neuropsychiatric manifestations, cardiac involvement and receiving CYC and high-dose steroids tended to be more frequent in those with secondary amenorrhea compared to those without. The median SLICC-DI was higher in those with amenorrhea compared to those without (p = 0.2) ConclusionCyclophosphamide is not the only key-player for the development of secondary amenorrhea in SLE; other factors as the shorter disease duration, presence of autoantibodies and major organ involvements may be implicated.

Osteopontin and interleukin-17A genes polymorphisms in Egyptian systemic lupus erythematosus patients: A relation to disease activity and severity

Osteopontin (OPN) is involved in the regulation of the immune response and is accused in the pathogenesis of several autoimmune diseases including systemic lupus erythematosus (SLE). An obvious link between OPN and T cells, particularly T helper 17 cells is reported, where OPN produced by dendritic cells supports interleukin-17 (IL-17) expression, contributing to pathology of autoimmune disorders. The aim of the study was to investigate the association of genotypes and alleles frequencies of OPN 9250 (rs1126616) and IL-17A 197 (rs2275913) genes polymorphisms with their serum levels, susceptibility, disease activity and severity in Egyptian SLE patients. A total of 80 SLE patients and 80 healthy subjects were enrolled. The PCR-RFLP technique was used to detect OPN 9250 C/T and IL-17A 197 G/A genes polymorphisms. Serum OPN and IL- 17 levels were measured by the enzyme-linked immunosorbent assay. OPN TT genotype and T allele were significantly detected in SLE patients more than controls (P = 0.003, P < 0.001 respectively). IL-17A AA genotype showed non-significant higher frequency in SLE patients than in their controls (P = 0.07). While only the A allele of IL-17A polymorphism was significantly elevated in patients (P = 0.048). There was statistical significant association between OPN CT and TT genotypes and both renal and mucocutaneous manifestations. Also IL-17A AG and AA genotypes was significantly associated with renal, mucocutaneous in addition to the hematological manifestations. Serum OPN levels were significantly increased with TT genotype while serum IL-17 levels were significantly increased with AA genotype. Disease activity and severity scores were significantly elevated with both OPN TT and IL-17A AA genotypes. In conclusion, OPN 9250 C/T and IL-17A 197 G/A genes polymorphisms and their serum levels seemed to have a role in pathogenesis of SLE.

Role of syndecan-1 (CD138) in Egyptian systemic lupus erythematosus patients with lupus nephritis: Relation to disease activity

BackgroundSyndecan-1, a transmemebrane heparan-sulfate glycoprotein, is predominantly expressed by plasma cells and is readily shed and released under certain pathologic conditions and remains biologically active to plasma cells behaviour. Aim of the workTo assess the level of syndecan-1 in relation to lupus nephritis (LN) and systemic lupus erythematosus (SLE) activity. Patients and methodsThe study included 60 SLE patients subgrouped according to the presence of LN and activity. SLE disease activity index (SLEDAI) was assessed. Serum syndecan-1 level was measured. ResultsThe patients mean age was 25.9 ± 8.6 years, they were 54 females and 6 males with a disease duration of 3.8 ± 3.4 years. There was a significant difference in the level of syndecan-1 between healthy control (46.3 ± 12.2 ng/ml) and SLE patients whether they were with active LN (150.2 ± 31.1 ng/ml) (p < 0.001), extrarenal flare (86.9 ± 16.7 ng/ml) (p < 0.001) or inactive (79.1 ± 19.8 ng/ml) (p < 0.003). Syndecan-1 was significantly higher in patients with active LN compared to those with extrarenal flare and inactive disease (p < 0.001 and p < 0.001 respectively). Serum syndecan-1 level was significantly higher in patients with arthralgia, arthritis, pleurisy and pericarditis) (all p < 0.001). There was a significant correlation between syndecan-1 level and 24 h urinary proteins (r = 0.8, p < 0.0001), and inversely with the complement (C3: r = −0.54, p < 0.0001 and C4: r = −0.48, p < 0.0001). There was a significant correlation between syndecan-1 and SLEDAI (r = 0.68, p < 0.001). ConclusionSerum syndecan-1 is significantly high in active LN patients and can be a useful tool for diagnosis of active nephritis. It correlates with disease activity, consumed complement and proteinuria. It was significantly related to the presence of musculoskeletal manifestations and serositis.

Risk factors for osteonecrosis severity among Egyptian systemic lupus erythematosus patients: Magnetic resonance imaging (MRI) staging

Aim of the workTo determine the risk factors of bilateral and severe (advanced) osteonecrosis femoral head (ONFH) as assessed by magnetic resonance imaging (MRI) staging in Egyptian SLE patients. Patients and methodsSixty SLE patients were studied and subdivided into two groups according to the presence or absence of symptomatic osteonecrosis. Full medical history, musculoskeletal examination, laboratory and serologic tests were done to all patients. SLE disease activity index (SLEDAI), systemic lupus international collaboration clinics damage index (SLICC/DI), health assessment questionairre (HAQ) disability index and the visual analogue scale (VAS-pain) were assessed. 30 patients with symptomatic ONFH were identified and staged by MRI according to Ficat and Arletclassification. Dual energy x-ray absorptiometry (DEXA) scan was performed. ResultsThe mean age at-onset of patients with ONFH was significantly lower than those without (20.7 ± 5.9 vs 30.4 ± 7.9 years; p < 0.0001) with comparable genders (F:M 29:1 vs 26:4; p = 0.16). SLEDAI, SLICC/DI, HAQ were significantly increased (p = 0.001 each) and DEXA reduced (p = 0.02) in those with ONFH. Predictors of ONFH severity included the presence of serositis (p = 0.005), arthritis (p = 0.02), gastrointestinal (GI) manifestations (p = 0.005), cardiac involvement (p = 0.049), diabetes (p = 0.01), elevated creatinine (0.008), urine sediments (p = 0.006), VAS-pain (p = 0.005), steroids (p = 0.015) and absence of hydroxychloroquine (HCQ) intake (p = 0.045). Risk factors of bilateral ONFH were the presence of serositis, nephritis, increased SLICC/DI and increased VAS-pain (p = 0.02, p = 0.03, p = 0.009 and p = 0.008, respectively). ConclusionNephritis, serositis, GI involvement, arthritis, steroids are key predictors for advanced ONFH while HCQ was protective. Risk factors for bilateral ONFH were serositis, nephritis, increased damage-index and VAS-pain.

Prognostic role of plasma cell free DNA in a cohort of Egyptian systemic lupus erythematosus patients

Background: Cell death has an important event in lupus pathogenesis as it leads to release of antigens as nucleic acids for immune complex formation. DNA-antibody complexes in the circulation are one of the hallmarks of Systemic Lupus Erythematosus (SLE) that leads to the clinical manifestations of SLE. Fluctuation in circulating DNA level might be one of the driving factors behind flare-ups. The objective of this study is to estimate the prevalence of plasma circulating cell-free deoxyribonucleic acid (cf DNA) in SLE patients and evaluate it as a prognostic marker in SLE and its relation to drug therapy. Methods: A case control study conducted on 75 Egyptian SLE patients divided into 2 groups; 45 SLE patients on therapy and 30 SLE patients recently diagnosed (without therapy) and 25 matched healthy control group. All patients are subjected to detailed medical history and clinical examination. Disease activity was done using SLEDAI-2k, related laboratory investigations in addition to estimation of cf-DNA concentration by real-time PCR technique. Findings: On comparing the 2 SLE groups, there was significant increase in nephritis, neuropsychiatric manifestations, vasculitis, fever, SLEDAI -2k, ESR, ANA, Anti-DNA titre and cf-DNA concentration and significant decrease in TLC, Hb, PLT, C3 and C4 in SLE without therapy than those on therapy (P<0.001). On comparing the 3 studied groups there was significant increase in cf-DNA concentration in SLE patients without therapy than those on therapy than in the control group (p <0.001). There was a significant correlation between cf-DNA concentration and neuropsychiatric manifestations, nephritis, fever, ESR, lymphopenia, anemia, thrombocytopenia, ANA titre, Anti-DNA titre, C3, C4 levels and SLEDAI -2k in all SLE patients (p <0.001). Conclusion: Plasma level of cf-DNA is significantly increased in SLE patients especially before starting therapy, so cf-DNA can be used as a marker of disease activity and treatment follow-up.