Comorbidities among Egyptian systemic lupus erythematosus: The COMOSLE-EGYPT study.

OBJECTIVE: To study the prevalence and impact of comorbidities among a cohort of patients with systemic lupus erythematosus (SLE). METHODS: This study is retrospective, multicenter including 902 Egyptian patients with SLE. Medical records were reviewed for demographic data, clinical characteristics, routine laboratory findings, immunological profile, and medications. Moreover, SLE Disease Activity Index (SLEDAI), and the Systemic Lupus International Collaborating Clinics/American College Rheumatology Damage Index scores were calculated. RESULTS: Comorbidities were found in 75.5% of the studied group with hypertension and dyslipidemia as the most frequent comorbidities (43.1% and 40.1%, respectively), followed by sicca features, avascular necrosis, diabetes, osteoporosis and renal failure (11.5%,9%, 9%,8.9%, and 7.1%, respectively). Multivariate regression model showed statistically significant relation between the presence of comorbid condition and each of age (P = 0.006), disease duration (P = 0.041), SLEDAI at onset (P < 0.001), cyclophosphamide intake (P = 0.001), and cumulative pulse intravenous methylprednisone (P < 0.001). Also, when adjusted to age and sex, those with multiple comorbid conditions had 18.5 increased odds of mortality compared to those without comorbidities (odds ratio (OR), 95% confidence interval (CI) = 18.5 (6.65-51.69)]. CONCLUSION: Patients with SLE suffer from several comorbidities, with an increasing risk with age, longer disease duration, higher SLEDAI at onset, cyclophosphamide intake and cumulative pulse intravenous methylprednisone. Risk of mortality is exponentiated with multiple comorbidities.

Analysis of Nuclear Receptor Coactivator 5 (NCOA5) Messenger RNA Expression and rs2903908 Single Nucleotide Polymorphism of NCOA5 in an Egyptian Cohort with Behçet's Disease: A Single-Center Case-control Study.

The nuclear receptor coactivator 5 (NCOA5) has been linked to several inflammatory disorders, including Behçet's disease (BD). We evaluated the expression of NCOA5 messenger RNA (mRNA) using real-time reverse transcription-polymerase chain reaction, and analyzed the rs2903908 T > C of NCOA5 using TaqMan allelic discrimination assay in 49 Egyptian BD patients and 50 controls. The NCOA5 mRNA levels were higher in patients compared to controls (p = .02), female patients compared to males (p = .037), and in patients with ocular involvement (p = .049). Non-CC genotype carriers had a higher frequency of articular manifestations compared with CC carriers (p = .047). Genotypes CC + CT were associated with reduced risk of cutaneous involvement (OR = 0.27, p = .04). CC carriers with active BD or cutaneous manifestations displayed significantly lower NCOA5 mRNA expression than TT carriers. Our results demonstrate that NCOA5 is linked to BD clinical findings and activity.

Role of miR-146a rs2910164 and UTS2 rs228648 Genetic Variants in Behçet's Disease.

BACKGROUND: Behçet's disease (BD) is a chronic autoimmune inflammatory disease. Clinical studies revealed that both microRNAs and urotensin II (UTS2) play a significant role in the development of autoinflammatory diseases. PURPOSE: The study aimed to determine the association between miR-146a rs2910164 and UTS2 rs228648 genetic variants and BD susceptibility. In addition, the relationship between these gene variants and clinical and laboratory outcomes among Egyptian patients was investigated. METHODS: The distributions of miR-146a rs2910164 and UTS2 rs228648 (p.Thr21Met) variants were analyzed in 94 patients with BD and 115 healthy control subjects using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Taqman Real-time PCR techniques. RESULTS: Frequencies of the G/G genotype and G allele of miR-146a rs2910164 variant were significantly higher in patients with BD compared with normal controls (p = .042, OR = 2.31; p = .022, OR = 1.58, respectively). The frequencies of the Thr/Thr genotype and the Thr allele of UTS2 rs228648 variant were significantly higher in subjects with BD compared with normal controls (p = .028, OR = 3.35; p = .032, OR = 1.60, respectively). CONCLUSION: Our results suggest that miR-146a rs2910164 and UTS2 rs228648 variants have significant roles in both the development and clinical modulation of BD in Egyptian patients.

Vasculitis damage index in Behçet's disease.

BACKGROUND: Vasculitis damage index (VDI) is a validated damage index for systemic vasculitis, and as Behçet's disease is considered one of systemic vascular disease we aimed to study the relationship of the vasculitis damage index to clinical manifestations and comorbidity in patients with Behçet's disease (BD) to determine if VDI could be used to assess damage in patients with BD. METHODS: A total of 109 patients with BD were recruited from the Rheumatology Department (outpatient and inpatient clinic), Cairo University Hospitals. All patients were subjected to full history taking, clinical examination, and routine laboratory investigations. Disease activity was assessed by the BD current activity form, and the VDI was calculated in all patients. The relationship of the VDI to the disease clinical manifestations was studied. Mann-Whitney and Kruskal Wallis tests were used to estimate differences in quantitative variables. Spearman correlation test was used to test for correlation between quantitative variables. RESULTS: In the current study, the VDI ranged from 1 to 10, with a mean of 3.5 ± 1.8. It was significantly associated with total thrombosis (P = 0.022); total neurological manifestations (P = 0.000), especially stroke and cranial nerve affection; uveitis (P = 0.005); avascular necrosis (AVN) (P = 0.015); osteoporosis (P = 0.01); impaired vision (P < 0.0001); cataract (P < 0.0001); and diabetes (P = 0.012). Generally, immunosuppressive treatment was significantly associated with VDI (P = 0.039), especially cyclophosphamide (P < 0.0001), biological agent (P = 0.008), chlorambucil (P = 0.003), and anticoagulant (P = 0.02). VDI was also significantly correlated with age (P = 0.033), disease duration (P = 0.029), and duration of eye involvement (P = 0.003). CONCLUSION: VDI is significantly associated with most disease parameters of BD, except for parameters such as mucocutaneous manifestations and uncomplicated venous thrombosis; however, further studies may be needed to establish BD-specific damage index.

Evaluation of serum microRNA-30e-5p expression in systemic lupus erythematosus and its association with clinical manifestations: A cross-sectional study / Evaluación de la expresión del microARN-30e-5p sérico en el lupus eritematoso sistémico y su asociación con las manifestaciones clínicas: un estudio transversal

ABSTRACT Background: MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression post-transcriptionally. Accumulating evidence indicates that the miR-30 family takes part in the development of multiple tissues and organs, and is a potential contributor to various dis eases, including autoimmune disorders such as systemic lupus erythematosus (SLE). The aim of this study was to evaluate the expression of miR-30e-5p, a member of the miR-30 fam ily, and investigate its potential relationship to clinical characteristics and possible disease activity in an Egyptian SLE cohort. Methods: Serum samples from 40 SLE patients and 37 age and gender matched healthy sub jects were tested for miR-30e-5p expression level using the Taqman quantitative reverse transcription-polymerase chain reaction. Analysis was performed using the 2 - AACT method. Results: The mean age of the patients was 28.7 ± 7.9 years, with a mean disease duration of 6.4 ±5.3 years. The median fold change in serum miR-30e-5p among our SLE cohort was significantly higher 1.748 (0.223-20.485) compared to the control group 0.877 (0.058-3.522) (P = 0.02). Receiver operating characteristic curve analysis revealed that miR-30e-5p expres sion level can discriminate SLE patients from controls at a cut-off value >1.06 with the area under the curve (AUC) = 0.676 (95% CI: 0.559-0.794, P = 0.02), with 64.3% sensitivity and 61.5% specificity. There was no correlation between any of the demographic features, clinical manifestations (apart from serositis, P = 0.013) or disease activity and miR-30e-5p levels. Conclusion: Our study demonstrated elevated miR-30e-5p expression levels in serum sam ples of SLE patients. Apart from serositis, it was not associated with any other disease characteristics.

RESUMEN Antecedentes: Los microARN (miRNA) son ARN no codificantes que regulan la expresión de los genes después de la transcripción. Las pruebas acumuladas indican que la familia de miR-30 participa en el desarrollo de múltiples tejidos y órganos, y es un posible contribuyente a diversas enfermedades, incluidos los trastornos autoinmunes como el lupus eritematoso sistémico (LES). El objetivo de este estudio fue evaluar la expresión del miR-30e-5p, un miembro de la familia miR-30, e investigar su posible relación con las características clínicas y la posible actividad de la enfermedad en una cohorte egipcia de LES. Métodos: Se analizaron muestras de suero de 40 pacientes con LES y 37 sujetos sanos de edad y sexo similares para determinar el nivel de expresión de miR-30e-5p, utilizando la reacción en cadena de la polimerasa de transcripción inversa cuantitativa Taqman. El análisis se llevó a cabo empleando el método 2-AACT. Los resultados: La edad media de los pacientes fue de 28,7 ± 7,9 años, mientras que la duración media de la enfermedad fue de 6,4 ± 5,3 años. La mediana del cambio de pliegue del suero miR-30e-5p entre nuestra cohorte de LES fue significativamente mayor, 1,748 (0,223-20,485), en comparación con el grupo de control, 0,877 (0,058-3,522) (p = 0,02). El análisis de la curva característica de funcionamiento del receptor reveló que el nivel de expresión del miR-30e-5p puede discriminar a los pacientes con LES de los controles en un valor de corte > 1,06, con el área bajo la curva (AUC) = 0,676 (IC del 95%: 0,559-0,794; p = 0,02), una sensibilidad del 64,3% y una especificidad del 61,5%. No hubo asociación entre ninguna de las características demográficas, manifestaciones clínicas (aparte de la serositis, p = 0,013) o actividad de la enfermedad y los niveles de miR-30e-5p. Conclusión: Nuestro estudio demostró niveles elevados de expresión de miR-30e-5p en mues tras de suero de pacientes con LES. Aparte de la serositis, no se asoció con ninguna otra característica de la enfermedad.

Vasculitis damage index in Behçet's disease

Abstract Background: Vasculitis damage index (VDI) is a validated damage index for systemic vasculitis, and as Behçet's disease is considered one of systemic vascular disease we aimed to study the relationship of the vasculitis damage index to clinical manifestations and comorbidity in patients with Behçet's disease (BD) to determine if VDI could be used to assess damage in patients with BD. Methods: A total of 109 patients with BD were recruited from the Rheumatology Department (outpatient and inpatient clinic), Cairo University Hospitals. All patients were subjected to full history taking, clinical examination, and routine laboratory investigations. Disease activity was assessed by the BD current activity form, and the VDI was calculated in all patients. The relationship of the VDI to the disease clinical manifestations was studied. Mann-Whitney and Kruskal Wallis tests were used to estimate differences in quantitative variables. Spearman correlation test was used to test for correlation between quantitative variables. Results: In the current study, the VDI ranged from 1 to 10, with a mean of 3.5 ± 1.8. It was significantly associated with total thrombosis (P = 0.022); total neurological manifestations (P = 0.000), especially stroke and cranial nerve affection; uveitis (P = 0.005); avascular necrosis (AVN) (P = 0.015); osteoporosis (P = 0.01); impaired vision (P < 0.0001); cataract (P < 0.0001); and diabetes (P = 0.012). Generally, immunosuppressive treatment was significantly associated with VDI (P = 0.039), especially cyclophosphamide (P < 0.0001), biological agent (P = 0.008), chlorambucil (P = 0.003), and anticoagulant (P = 0.02). VDI was also significantly correlated with age (P = 0.033), disease duration (P = 0.029), and duration of eye involvement (P = 0.003). Conclusion: VDI is significantly associated with most disease parameters of BD, except for parameters such as mucocutaneous manifestations and uncomplicated venous thrombosis; however, further studies may be needed to establish BD-specific damage index.

Choroidal Thickness and microRNA146 in Lupus Nephritis Patients.

PURPOSE: To evaluate the choroidal thickness (CT) in the macular area in patients with lupus nephritis and to compare the results with both non-nephritic patients and normal control. To assess the relation of CT to serum microRNA146, disease duration, activity index, and medications. PATIENTS AND METHODS: Thirty-five SLE patients and thirty normal healthy controls were enrolled for this cross-sectional prospective study. All participants have undergone optical coherence tomography using RTVue OCT (Optovue Inc., Fremont, CA, USA). The scan used was the macular cross 6-mm line. We measured CT from the posterior edge of the retinal pigment epithelium (RPE) to the choroid-sclera junction at subfovea, and 750 µm both temporal and nasal to the fovea. RESULTS: The mean central subfoveal CT in patients was 275.7 ± 41.0 µm (214-374 µm), and the mean central subfoveal CT in the control group was 364.5± 23.0 µm (323-411µm). There was a significant thinning at all three points in patients compared to the control group (p<0.001, Mann-Whitney U-test). In the patients group, subfoveal choroid in non-nephritic subgroup showed significant thinning compared to nephritic subgroup (p=0.032, Mann-Whitney U-test). Drusen-like deposits (DLDs) were detected in 22.9% (8/35) of patients and none in control (p=.023). MiRNA146 showed a significant positive correlation with nephritic lupus patients (r=0.036, P=0.04). CONCLUSION: The choroidal thickness was significantly thicker among the nephritic lupus patients as compared to the non-nephritic subgroup. Both SLE patients' subgroups are thinner than normal control. Subfoveal choroidal thickening can be considered a biomarker in nephritic lupus especially in conjunction with an increase in miRNA146a. All SLE patients are at risk of small Drusen-like deposits.

Growth Differentiation Factor-15 (GDF-15) Level and Relation to Clinical Manifestations in Egyptian Systemic Sclerosis patients: Preliminary Data.

AIM OF THE WORK: This study aims to assess Growth differentiation factor-15 (GDF-15) level in Scleroderma patients and its relation to disease manifestations. PATIENTS AND METHODS: This study included 55 scleroderma patients and 40 age and sex matched healthy volunteers. All patients were subjected to full history taking, thorough clinical examination, and laboratory investigations. GDF-15 serum levels were analyzed in patients and controls using human GDF-15 immunoassay Quantikine ELISA kit. RESULTS: The GDF-15 serum level was significantly higher in Systemic sclerosis (SSc) patients in comparison to healthy control individuals, p-value = 0.004. In addition, the GDF-15 serum levels increased in a significant way in patients with diffuse SSc than those with limited SSc, p = 0.026. Also, we had discovered a significant positive correlation between serum GDF-15 levels and the modified Rodnan score of the SSc patients, r = 0.442, p = 0.001 and a significant association was found between high GDF-15 level and SSc patients with interstitial pulmonary fibrosis (IPF) as compared to healthy controls (p = 0.002). However, no significant difference was found between SSc patients without IPF and healthy subjects regarding GDF-15 level (p = 0.106). CONCLUSION: GDF-15 serum levels were elevated in patients with SSc and correlated with the extent of skin fibrosis, and it was found to be higher in SSc patients with IPF. Such results may suggest a pivotal role of GDF-15 in fibrotic changes in SSc, and GDF-15 could be a treatment target in SSc patients in future.

Matrix Metalloproteinase-9 rs17576 Gene Polymorphism and Behçet's Disease: Is There an Association?

BACKGROUND: Clinical studies have reported a significant association between matrix metalloproteinases (MMP), particularly (MMP-9), and inflammatory diseases including Behçet's disease (BD). PURPOSE: To study the relationship between MMP-9 rs17576 gene polymorphism and the development of BD, and its relation to disease activity among Egyptian patients. METHODS: A total of 100 BD patients and 100 healthy control volunteers were genotyped for MMP-9 rs17576 polymorphism with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), followed by the confirmation of our results in random subgroups using direct DNA sequencing technique. RESULTS: The frequency of the GG genotype and G allele was significantly higher in BD patients as compared to the normal controls (p = 0.011, OR 8.61; p = 0.03, OR 1.65, respectively). There was no significant association between the MMP-9 rs17576 polymorphism and the clinical outcomes of BD. CONCLUSION: our study suggests a significant association of the MMP-9 rs17576 A/G polymorphism with increased risk of BD development in Egyptian patients.

The role of microRNA-31 and microRNA-21 as regulatory biomarkers in the activation of T lymphocytes of Egyptian lupus patients.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by familial aggregation and genetic predisposition. MicroRNAs (MiRNAs) serve as critical biomarkers in lupus patients because of their aberrant expression in different SLE stages. The study aimed to investigate the correlation of miR-31 and miR-21 with IL-2 in SLE patients as regulatory biomarkers in the activation of T lymphocytes of Egyptian lupus patients. Quantitative RT-PCR is carried out to estimate the expressions of miR-31 and miR-21, and IL-2 levels were determined using ELISA in plasma of 40 patients with SLE, 20 of their first-degree relatives and 20 healthy controls. The study also determined the systemic lupus erythematosus disease activity index (SLEDAI) score and proteinuria in SLE patients. The results revealed that miR-31 was lower expressed, while miR-21 was high expressed in SLE patients compared to their first-degree relatives and controls. MiR-31 was negatively correlated with SLEDAI and proteinuria in lupus patients, while miR-21 showed positive correlation with them. Also we found that there is a significant positive correlation between miR-31 and IL-2 in SLE patients, while miR-21 was negatively correlated with IL-2 level in patients. In conclusion, the study disclosed a significant association between miR-31 and miR-21 expression with IL-2 level in SLE patients. The regulatory biomarkers of miR-31 and miR-21 might have an impact on regulating IL-2 pathway expression and in turn on the activation of T lymphocytes in SLE.

Association of VDR ApaI and TaqI Gene Polymorphisms with the Risk of Scleroderma and Behçet's Disease.

Vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms have been reported in autoimmune diseases. However, their role in Behçet's disease (BD) and scleroderma remains inconclusive. Our aim was to evaluate vitamin D receptor (ApaI, TaqI) gene polymorphisms in relation to Behçet's disease and scleroderma in Egyptians. The study was conducted on 54 patients with BD, 30 scleroderma patients, and 60 healthy control subjects. VDR (ApaI, TaqI) gene polymorphisms were investigated using polymerase chain reaction-restriction fragment length polymorphism technique. The "a" allele of ApaI (A/a) polymorphism was significantly associated with increased BD risk (OR = 2.09, 95% CI = 1.18-3.71, p = 0.011), while the TaqI "tt" genotype was significantly lower in BD patients as compared to control subjects (OR = 0.35, 95% CI = 0.13-0.9, p = 0.026). Carriage of "aT" VDR haplotype was significantly associated with higher BD risk (OR = 2.28, 95% = 1.14-4.56, p = 0.022). In conclusion, our findings suggest that VDR gene polymorphisms have a significant association with BD in Egyptian patients.

Therapeutic antioxidant and anti-inflammatory effects of laser acupuncture on patients with rheumatoid arthritis.

BACKGROUND AND OBJECTIVE: The laser acupuncture has many potential therapeutic effects. Currently, they are not evaluated for their therapeutic effects on rheumatoid arthritis (RA) patients. The aim of this study was to investigate the effects of laser acupuncture on the oxidative and antioxidative markers, as well as the inflammatory markers and disease activity of RA patients. DESIGN/MATERIALS AND METHODS: The study was conducted on 30 RA patients and 20 healthy subjects. The patients were subjected to laser acupuncture (904 nm, 100 mW power output, 1 minute irradiation time, beam area of 1 cm(2) , total energy per point 6 J, energy density 6 J/ cm(2) , irradiance 0.1 W/cm(2) , frequency 10000 Hz, duty-cycle 100%) for 3 days/week for duration of 4 weeks. The acupuncture points of exposure were LI4, TE5, LI 11, DU 14, LIV3, SP6, GB34, and S36. The levels of oxidative and antioxidant markers were determined by spectrophotometric methods whereas the inflammatory markers were determined by ELISA methods. Lastly, using DAS28 scores the disease activity was assessed. RESULTS: After laser acupuncture, the study group revealed significantly increased plasma superoxide dismutase (SOD), glutathione reductase (GR), catalase activities, blood glutathione (GSH), and plasma ATP concentrations, compared to those before treatment (P < 0.0005). Moreover, the results revealed significantly reduced plasma malondialdehyde (MDA), serum nitrate and nitrite, serum C-reactive protein (CRP), plasma interleukin-6 (IL-6) levels and significantly reduced glutathione peroxidase (GPx) activity and erythrocyte sedimentation rate (ESR) in laser exposed patients, compared to those before treatment (P < 0.0005). The RA patients subjected to laser acupuncture showed highly significant reduction in disease activity (P < 0.0005) based on DAS28 score. CONCLUSION: Our study results confirmed the effectiveness of laser acupuncture in alleviating oxidative stress and inflammation, improving antioxidant and energy metabolic status, while also suppressing the disease activity in RA patients. Laser acupuncture is a promising treatment modality to reduce the pain and suffering of RA patients because of its efficiency in inhibiting most of the main factors involved in the pathogenesis of this disease. Lasers Surg. Med. 48:490-497, 2016. © 2016 Wiley Periodicals, Inc.