Human Complement C3 Protein, His Tag (MALS verified)

Abstract: Membranoproliferative glomerulonephritis, with its immune complex variety and C3 glomerulopathy, is a rare glomerular disease in children. The objective of this study was to determine the clinical features and short-term outcomes in children.This retrospective cohort study was conducted at the Department of Pediatric Nephrology, Sindh Institute of Urology and Transplantation, Karachi, from January 2020, to June 2022. All the children with membranoproliferative lesions identified via light microscopy and less than 18 years were included.A total of 35 children were diagnosed MPGN, 7 (20%) with C3 glomerulopathy and 28 (80%) idiopathic immune complex MPGN. In the IC-MPGN group, 14 patients (50%) had crescentic glomerulonephritis. Induction therapy consisted of cyclophosphamide and methylprednisolone followed by steroids, azathioprine was prescribed for maintenance phase. At the 18-month follow-up, 9 (64%) patients were in complete remission (CR), 3 (21%) were in partial remission (PR), and 2 (15%) progressed to chronic kidney disease. The remaining 14 (50%) had non-crescentic idiopathic IC-MPGN and were prescribed steroids only, cyclophosphamide with steroids and angiotensin converting enzyme inhibitors. The outcomes at 18 months were relatively poorer than those with the crescentic variety. Four (28%) patients achieved CR, 8 (56%) PR, and 2 (14%) did not respond. In the C3 glomerulopathy cohort, 3 (43%) had crescentic glomerulonephritis, one child was in CR, and two were in PR. The non-crescentic C3G were kept on ACEI 3 (43%) and Mycophenolate mofetil 1 (14%). One child treated with ACEIs achieved a PR, two were in CR, and one child treated with MMF did not respond.The outcome of MPGN (immune complex and C3G) is quite variable, and aggressive therapy for crescentic glomerulonephritis may show a favourable response. Considering the similar clinical presentations and patient outcomes, C3G and IC-MPGN might represent two facets of the same disease.© 2025. The Author(s).

Abstract: Acute post-streptococcal glomerulonephritis (APSGN) is the primary cause of acute glomerulonephritis in children in Nepal and contributes significantly to paediatric hospitalisations in the country. This review discusses the current status of streptococcal infections, epidemiological trends, and the challenges in diagnosing and managing APSGN in Nepalese children. This study aimed to develop local data on acute post-streptococcal glomerulonephritis to help compare epidemiological trends and patterns with regions where this disease is less prevalent.A targeted literature review was conducted in PubMed, Google Scholar, and Nepal Journals Online (a local database) to identify relevant literature published between 1 January 2000 and 31 December 2024. Additional searches of conference abstracts and reviews were performed using Google. The collected literature was analysed to determine the kidney disease patterns, current status of Group A Streptococcal infection, epidemiological trends, clinical manifestations, management, and outcomes of APSGN in Nepali children aged < 16 years.Thirty-four articles were selected for in-depth review. A synthesis of local hospital studies revealed significant differences in the application of diagnostic criteria for APSGN owing to the inaccessibility of serological tests and complement testing. Children over five years of age, particularly those aged 8 to 11 years and predominantly male, were more severely affected. The disease was present year-round, with pyoderma identified as the main route of preceding streptococcal infection rather than throat infection, particularly affecting economically disadvantaged children. The classical manifestations were oedema, hypertension, gross haematuria, and oliguria, whereas complications included acute kidney injury, rapidly progressive glomerulonephritis, hypertensive emergency, congestive cardiac failure, and the need for kidney replacement therapy. The anti-streptolysin O titre was positive in 34-72.7% of patients, while complement C3 levels were depressed in 61.9-100% of cases. Urinalysis showed haematuria in 67-100% of patients and pyuria in 7.9-37%. Kidney ultrasonography indicated increased echogenicity in 37-78% of the cases. Most patients were managed conservatively with diuretics and anti-hypertensives. Atypical cases and those with a progressive disease course were further managed with steroids, kidney biopsies, or kidney replacement therapy. Most patients exhibited favourable short-term kidney outcomes. There was low mortality among patients with rapidly progressive glomerulonephritis and those who required kidney replacement therapy.This review highlights that acute post-streptococcal glomerulonephritis remains a common cause of hospitalisation in Nepal. It remains a diagnostic difficulty owing to the inaccessibility of serological and complement tests. The disease has distinct clinical manifestations, demographic patterns, histological findings and outcomes in Nepali children.© 2025. The Author(s).

Abstract: Complement system activation is implicated in various stages of atherogenesis, from fatty streak formation to plaque destabilization and thrombus formation, with its dreadful clinical sequelae such as myocardial infarction, stroke and premature death. In this review, we consider these issues and explore recent studies on complement activation in atherosclerotic plaque initiation and progression.Complement pathways impact plaque stability and healing through the modulation of inflammatory processes. Recent studies indicate that complement components, notably C3 and C5b-9, accelerate atherosclerosis progression through their interactions with endothelial cells, smooth muscle cells, and immune cells. Nonetheless, the beneficial versus deleterious effects of complement activation at different stages of atherogenesis remains a matter of ongoing debates. Research also investigates therapies targeting the complement cascade to mitigate plaque erosion and rupture. This review explores the ongoing debates surrounding complement activation in atherogenesis. We bring forward controversial findings and therapeutic strategies aimed at modulating complement cascade activation with the ultimate goal to reduce the burden of atherosclerotic cardiovascular disease.\.© 2025. The Author(s).

Abstract: BackgroundV-set and immunoglobulin domain containing 4 (VSIG4) emerges as a significant player in the immune system pathways. It has been previously identified as a potential hub gene for Alzheimer's disease (AD) and aging, underscoring its importance in understanding these conditions.ObjectiveThis study aimed to evaluate the diagnostic potential of serum VSIG4 and identify trends in serum VSIG4 in relationship with other biomarkers and neurological tests.MethodsELISA was used to measure the serum concentration of VSIG4 in AD, compared to healthy subjects. The relationship between VSIG4 levels and the age of the subjects, as well as other AD-related serum proteins and various measures of cognition was examined.ResultsVSIG4 was significantly elevated in the serum of AD patients compared to healthy controls (p = 0.0074). Significant correlations were identified between serum VSIG4 and other notable proteins related to AD and inflammation, such as total tau, neurofilament light (NfL), YKL-40, CD14, FABP3, and TNF-α. Significant correlations were also identified between VSIG4 concentration and the results of neurological tests.ConclusionsSerum VSIG4 may reflect neuroinflammation and altered lipid processing, affecting the cognitive performance of AD and aging.