Evaluation of Immunity-related GTPase Family M Protein (IRGM) SNPs among Egyptian Lupus Patients: A Case-control Study.

OBJECTIVE: One of the potential factors that cause systemic lupus erythematosus (SLE) development is autophagy. Immunity-related GTPase family M protein (IRGM) has been shown to be linked to immune-mediated diseases. The aim of the current study was to assess the role of the IRGM-autophagy gene in SLE susceptibility in an Egyptian population and its relation to lupus nephritis. METHODS: A case-control study was conducted in which a total of 200 subjects (100SLE and 100 healthy controls) were enrolled. Two single-nucleotide polymorphisms (SNPs) (rs10065172 and rs4958847) were genotyped. Genotypes and alleles analysis was conducted to compare between cases and controls, as well as a stratification analysis was conducted on the presence or absence of lupus nephritis. RESULTS: Among selected SNPs of IRGM, no association was found between both SNPs and SLE susceptibility. For rs10065172, the major expressed genotype was CC (61% and 71%) (Adj OR= 2.9, 95%= 0.545-15.5), followed by TC (34% and 27%) (Adj OR= 1.985, 95% = 0.357-11.041) in cases and controls, respectively. For rs4958847, AA and AG were comparably expressed in case [(43% and 39%) (Adj OR= 1.073, 95% = 0.483-2.382)] and control [(41% and 43%) (Adj OR= 1.24, 95% = 0.557- 2.763)], respectively. Additionally, no relationship among both SNPs and gender, lupus nephritis, disease activity, or disease duration, was observed. CONCLUSION: IRGM SNPs (rs10065172 and rs4958847) expression was comparable among SLE patients and controls of the Egyptian cohort. Genotype and allele frequency of IRGM SNPs did not differ in lupus nephritis and non-lupus nephritis patients.

Assessment of Lupus Nephritis in a Multicenter Retrospective Egyptian Cohort: Initial Characteristics, Influence of Age and Gender, Outcome, and Potential Association with Disease Damage.

The study aimed to evaluate the association of demographic, clinical, and histopathologic characteristics with renal and disease outcomes. Persistent lack of partial or complete remission despite sequential induction therapy, chronic kidney disease (CKD) or endstage renal disease (ESRD), and/or mortality were determined as poor renal outcomes. Disease damage was investigated through the Systemic Lupus International Collaborating Clinics/ American College of Rheumatology Damage Index (SDI). Of 201 biopsy-proven lupus nephritis patients, a poor outcome was present in 56 (27.9%) patients, with nine (4.5%), 22 (10.9%), and 29 (14.4%) patients demonstrating lack of response, CKD, and ESRD, respectively, and the prevalence of mortality was 5.5% (11/201). The outcome was poor among males [29/201 (14.4%)] [P = 0.008; odds ratio (OR): 2.8; 95% confidence interval (CI): 1.2-6.4], yet comparable between adult- and juvenile-onset patients [80/201 (39.8%) (≤16 years)] (P = 0.6; OR: 0.8; 95% CI: 0.4-1.6). Hypertension (P <0.001; OR: 6.3; 95% CI: 2.6-14.9), elevated creatinine (P <0.001; OR: 5.2; 95% CI: 2.6-10.3), and hematuria (P <0.001; OR: 3.7; 95% CI: 1.9-7.5) at presentation, and fibrinoid necrosis [P <0.001; odds ratio (OR): 4.1; 95% confidence interval (CI): 2.1-8.1], wire loops (P = 0.006; OR: 2.4; 95% CI: 1.2-4.6), crescents (P <0.001; OR: 5.4 95% CI: 2.8-10.5), interstitial fibrosis (P = 0.001; OR: 2.7; 95% CI: 1.4-5.1), and acute vascular lesions (P = 0.004; OR: 3.6; 95% CI: 1.4-9.4) on biopsy were associated with a poor outcome. Chronic glomerular (P = 0.003) and acute vascular lesions (P <0.001), and a higher chronicity index (r = 0.1; P = 0.006) on biopsy, and frequent renal (r = 0.3; P <0.001) and extra-renal flares (r = 0.2; P <0.001) were associated with higher SDI scores. Among the studied renal and extra-renal parameters, independent predictors of higher disease damage solely included frequent renal flares (ᵝ= 1; P <0.001). To conclude, a poor renal outcome (27.9%) was associated with distinct features. Disease damage was associated with frequent renal flares.

Sarcoidosis beyond pulmonary involvement: A case series of unusual presentations.

Unusual presentations of sarcoidosis pose a diagnostic challenge and warrant attention. Hematologic associations: Case 1 (37-years-old male): Pancytopenia: myelofibrosis (leading to sepsis and mortality) following a two-year quiescent course of biopsy-proven-sarcoidosis. Case 2 : (38-years-old male): Presentation with thrombocytopenia (5 × 103/cmm): immune thrombocytopenic purpura (histologically associated with megakaryocytic emperipolesis). Biopsied enlarged lymph nodes demonstrated sarcoidosis. Hematologic sarcoid involvement is usually due to granulomatous bone marrow (3.9%) or splenic infiltration (6-30%); however, the presented manifestations are scarcely reported with a potential significance that is yet to be elucidated. Case 3: Neurologic presentation: 48-years-old female: presentation with bilateral sensorineural hearing loss and facial palsy. Brain magnetic resonance imaging showed leptomeningeal thickening. Biopsied enlarged lymph nodes showed sarcoidosis. Case 4: Neurologic and renal manifestations: 13-years-old male (family history of sarcoidosis): Presenting with acute headache, investigations showed elevated serum creatinine (2.1 mg/dL) and angiotensin converting enzyme, and computed tomography chest and abdominal findings characteristic of sarcoidosis. Associated benign increased intracranial and acute tubulointerstitial nephritis (with eosinophils) were diagnosed upon concordant workup. Of sarcoidosis neurologic affection (5-10%), cranial nerve(s) involvement is among the most common (25-50% of neurosarcoid affection), particularly that of the facial nerve (Case 3). Leptomeningeal enhancement is among the most common neurosarcoid radiologic findings (30-40%). Whereas benign increased intracranial tension (Case 4) is much less reported. Among sarcoidosis renal involvement (35-50%), interstitial nephritis usually presents with granulomatous renal lesions, yet its sole association with sarcoidosis is unusual (Case 4). The portrayed atypical hematologic, neurologic, and renal manifestations further emphasize the masquerading nature of sarcoidosis.

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.

Characteristics, evolution, and outcome of patients with non-infectious uveitis referred for rheumatologic assessment and management: an Egyptian multicenter retrospective study.

OBJECTIVE: To investigate the characteristics, evolution, and visual outcome of non-infectious uveitis. METHODOLOGY: Records of 201 patients with non-infectious uveitis (136 (67.7%) males and 84 (41.8%) juvenile-onset (≤ 16 years)) were retrospectively reviewed. Data were analyzed through Kruskal-Wallis and Mann-Whitney, chi-square (χ2) tests, and logistic regression. RESULTS: The median disease and follow-up durations were 36 (interquartile range (IQR) 24-70) and 24 (IQR 10-36) months, respectively. Fifty-eight (28.9%) patients had persistently idiopathic uveitis, and 143 (71.1%) were associated with rheumatic diseases, of whom uveitis heralded, coincided with, and succeeded the rheumatic manifestation(s) in 62/143 (43.4%), 37/143 (25.9%), and 44/143 (30.7%) patients, respectively. Established rheumatic diseases were Behçet's disease (103/201 (51.2%)), juvenile idiopathic arthritis (13/201 (6.5%)), sarcoidosis (8/201 (4%)), seronegative spondyloarthropathy (7/201 (3.5%)), and Vogt-Koyanagi-Harada (7/201 (3.5%)), and other diagnoses were present in 5/201 (2.5%) patients. Patients with idiopathic uveitis were characterized by a juvenile-onset (p < 0.001), lower male predominance (p = 0.01), prevalent granulomatous (p < 0.001), and anterior (p = 0.001) uveitis. The median visual acuity at last visit was 0.3 (IQR 0.05-0.6). Visual loss was present in 45/201 (22.3%) patients (36/201 (17.9%) unilateral and 9/201 (4.4%) bilateral). Apart from a longer disease duration (p = 0.002), lower educational level (p = 0.03), and prevalent panuveitis (p < 0.001), visual loss was not associated with any other studied ocular or extra-ocular characteristics. CONCLUSION: Behçet's disease (51.2%) and idiopathic uveitis (28.9%) were the most prevalent causes of non-infectious uveitis in our study. Visual loss (22.3%) was associated with a longer disease duration, lower education level, and prevalent panuveitis. Key Points • Most common causes of uveitis referred to rheumatologists were Behçet's disease and idiopathic uveitis. • Several rheumatic diseases initially presented only with uveitis, more commonly in adult and male patients. • Panuveitis was more frequent among patients with an established rheumatic disease, whereas granulomatous uveitis was uncommon. • Longer disease duration and presence of panuveitis were independently associated with visual loss.