Renal involvement in Systemic Lupus Erythematous (SLE) patients is one of the leading causes of morbidity and a significant contributor to mortality. It’s estimated that nearly 50% of SLE individuals develop kidney disease in the first year of the diagnosis. Class IV lupus nephritis (LN-IV) is the class of lupus nephritis most common in Colombian patients with SLE. Altered miRNAs expression levels have been reported in human autoimmune diseases including lupus. Variations in the expression pattern of peripheral blood circulating miRNAs specific for this class of lupus nephritis could be correlated with the pathophysiological status of this group of individuals. The aim of this study was to evaluate the relative abundance of circulating microRNAs in peripheral blood from Colombian patients with LN-IV. Circulating miRNAs in plasma of patients with diagnosis of LN-IV were compared with individuals without renal involvement (LNN group) and healthy individuals (CTL group). Total RNA was extracted from 10 ml of venous blood and subsequently sequenced using Illumina. The sequences were processed and these were analyzed using miRBase and Ensembl databases. Differential gene expression analysis was carried out with edgeR and functional analysis were done with DIANA-miRPath. Analysis was carried out using as variables of selection fold change (≥2 o ≤-2) and false discovery rate (0.05). We identified 24 circulating microRNAs with differential abundance between LN-IV and CTL groups, fourteen of these microRNAs are described for the first time to lupus nephritis (hsa-miR-589-3p, hsa-miR-1260b, hsa-miR-4511, hsa-miR-485-5p, hsa-miR-584-5p, hsa-miR-543, hsa-miR-153-3p, hsa-miR-6087, hsa-miR-3942-5p, hsa-miR-7977, hsa-miR-323b-3p, hsa-miR-4732-3p and hsa-miR-6741-3p). These changes in the abundance of miRNAs could be interpreted as alterations in the miRNAs-mRNA regulatory network in the pathogenesis of LN, preceding the clinical onset of the disease. The findings thus contribute to understanding the disease process and are likely to pave the way towards identifying disease biomarkers for early diagnosis of LN.
1 September 2023 in American Journal of Perinatology Reports
Pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS) is a rare condition characterized by microangiopathic hemolytic anemia and kidney injury from thrombotic microangiopathy. P-aHUS occurs in approximately 1 in 25,000 pregnancies and is strongly related to complement dysregulation and pregnancy-related disorders, such as preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, low platelet (HELLP) syndrome, resulting in adverse perinatal and fetal outcomes. Complement dysregulation in P-aHUS is commonly attributed to genetic mutations or autoantibodies affecting complement factors, including CFH, CFI, and MCP. We present a case of a 25-year-old primigravida who experienced severe preeclampsia and HELLP syndrome followed by the development of complicated P-aHUS during the early postpartum period. The patient exhibited severe clinical manifestations, including hypertensive emergency, central nervous system involvement, renal impairment, and microangiopathic hemolytic anemia. Timely initiation of eculizumab therapy resulted in successful disease remission. Further genetic analysis revealed a likely rare pathogenic MCP gene variant.
23 September 2022 in Allergologia et Immunopathologia
Introduction: Chronic spontaneous urticaria (CSU) is an inflammatory skin disease related to poor quality of life. Previous studies have found that vitamin D deficiency and vitamin D recep-tor (VDR) TaqI, BsmI, FokI, and ApaI gene single-nucleotide polymorphisms (SNPs) influence immune response and susceptibility to skin disorders. Aim: To explore the role of VDR SNPs, and the association of vitamin D serum levels in a sample of Colombian Caribbean CSU patients. Methods: It is a case-control study. A group of CSU patients (n = 100) was compared with healthy individuals as a control group (n = 100). VDR polymorphisms were genotyped by quantitative polymerase chain reaction and Taqman® probes. Allelic, genotypic, and haplotype associations were estimated. Serum vitamin D levels were measured using enzyme-linked-immunosorbent serologic assay. Results: Compared to the control group, the presence of G allele in TaqI and A allele in FokI SNPs of VDR gene was found to be a risk factor for CSU (odds ratio (OR) estimated using logistic regression adjusted by gender: 2.08 and 1.61, respectively, all P values < 0.05). The individuals who carry GCCA haplotype showed decrease in vitamin D levels (11.34 ng/mL; P = 0.002) with the G allele of TaqI and A allele of FokI gene SNPs. Conclusion: We reported for the first time the association of TaqI [rs731236] and FokI [rs2228570] VDR gene SNPs showing as a risk factor for CSU in a sample of multiethnic patients from the Colombian Caribbean population.
Background: As with many other chronic diseases, systemic lupus erythematosus (SLE) and lupus nephritis (LN) have significant impacts on the health-related quality of life (HRQoL). Medication non-adherence is a significant challenge in the management of SLE, with consistently up to 75% of patients being non-adherent with their SLE medications. There is a need to assess the patient’s perspective using patient-reported outcomes (PROs) to better understand the current impact of LN on HRQoL and treatment adherence in our region. The aim of this study was to explore the relationship between HRQoL and treatment adherence in patients with LN from the Colombian Caribbean. Methods: A cross-sectional study was conducted from June to December 2022, including patients with biopsy-proven LN. HRQoL and treatment adherence were assessed using the Lupus Quality of Life (LupusQoL) and the Compliance Questionnaire in Rheumatology 19 (CQR19) instruments, respectively. Patients were categorized as adherent or non-adherent based on medication intake (defined as >80% correct dosage). Principal component analysis (PCA) was employed to identify principal components between adherent and non-adherent patients. Results: A total of 42 patients with LN were included. Of these, 38 (90%) were female, and the mean age was 31 ± 10 years. Proliferative class IV was the predominant histopathological profile (90%). Twenty-five (60%) patients were categorized as non-adherent. Across all LupusQoL domains, a comprehensive range of responses was observed. Pain, planning, and intimate relationships domains remained unaffected, while burden to others domain had the lowest score. Poorer planning score correlated with older age (r = −0.72; p < .05) and longer disease duration (r = −0.74; p < .05). SLEDAI-2 K correlated with the pain domain (r = −0.78; p < .05). Non-adherent patients exhibited significantly worse pain domain scores compared to adherent counterparts ( p < .05). PCA showed strong interactions between planning and pain, as well as between physical health and body image domains. Conclusions: LupusQoL pain domain scores were significantly worse in non-adherent patients compared to adherent patients. Effective pain management could be a determinant in HRQoL and treatment adherence rates in our population.
Lupus nephritis represents a significant immune-mediated glomerulonephritis, constituting the most important organ involvement induced by systemic lupus erythematosus (SLE), with variable epidemiology and clinical presentation among populations. Objective: to identify clinical and immunological factors associated with the progression of lupus nephritis in a population from the Colombian Caribbean. Methods: we evaluated 401 patients diagnosed with SLE and lupus nephritis, treated at a reference center in the Colombian Caribbean, gathering data recorded in medical records. Results: A proportion of 87% were female, with a median age of 42 years. Most patients presented with proliferative classes (90%), with class IV being the most common (70%). A proportion of 52% of patients did not respond to treatment, which is described as the lack of complete or partial response, while 28% had a complete response. A significant decrease in hemoglobin, glomerular filtration rate, and proteinuria was identified by the third follow-up (p < 0.001), along with an increase in creatinine, urea, and hematuria (p < 0.001). Patients with initial proteinuria > 2 g/day were found to be 27 times more likely to be non-responders (p < 0.001). Mortality was associated with the presence of serum creatinine >1.5 mg/dL (p = 0.01) (OR: 1.61 CI 95% 0.75–3.75) and thrombocytopenia (p = 0.01) (OR: 0.36; CI 95% 0.12–0.81). Conclusions: identifying factors of progression, non-response, and mortality provides an opportunity for more targeted and personalized intervention, thereby improving care and outcomes for patients with lupus nephritis.
Background and aims Lupus Nephritis is one of the most serious complications of SLE with a prevalence of 65%, it is diagnosed in the first five years of SLE and is uncommon after 10 years. Between 5% and 25% of cases have Chronic Renal Disease (CKD) after 5 years. Methods NEFRORED begins in 2008 as a multicenter registry of prospective observational cohorts, which includes patients with confirmed diagnosis of NL through renal biopsy. Study the incidence of the clinical and pathological characteristics of NL in the Colombian Caribbean region. The database was implemented with the variables of the clinical records of the patients. Results Eight centres were involved and 400 patients have been included, 88% female; ratio between men and women is 7:1 with a median age 37 years. Urinary parameters have evidenced 24 hours mean proteinuria of 1.9±3.3g/24 hours and microscopic hematuria in 50% of patients. Among nephrological syndromes, nephritic syndrome and hematuria-proteinuria have been the most frequent 70%, followed by nephrotic syndrome and non-nephrotic proteinuria 30%. Hypocomplementemia is evidenced in 60% of the patients. The median of the SLEDAI has been 10.2 points. Antinuclear Antibodies are positive in 90%. NL class IV-G (A) has been the most frequent 75%. Chronic Renal Disease is concomitant in 52% of the cases. Conclusions NEFRORED represents the first Colombian cohort of patients diagnosed with NL, with up-to-date information on the renal manifestations of SLE, comorbidities, disease status and clinical evolution under conditions of real clinical practice. CKD remains a significant comorbidity in patients with NL.