UNASSIGNED: The aim of this study was to investigate the potential importance of complement system activation, with particular emphasis on the complement alternative pathway (AP), in the pathogenesis of hypertensive renal damage.
UNASSIGNED: Serum complement C3, complement Factor H (CFH) and AP activation were assessed in 66 participants with established essential hypertension with renal damage (RD). Fifty-nine patients with age- and sex-matched essential hypertension without renal damage (NRD) and 58 healthy participants (normal) were selected.
UNASSIGNED: Our study revealed that C3 and AP50 continuously increased from normal to NRD to RD (p < 0.05, respectively), while CFH was significantly lower than that in NRD and healthy participants (p < 0.05, respectively). After multifactorial logistic regression analysis corrected for confounders, elevated serum C3 (p = 0.001) and decreased CFH (p < 0.001) were found to be independent risk factors for hypertension in healthy participants; elevated serum C3 (p = 0.034), elevated AP50 (p < 0.001), decreased CFH (p < 0.001), increased age (p = 0.011) and increased BMI (p = 0.013) were found to be independent risk factors for the progression of hypertension to hypertensive renal damage; elevated serum C3 (p = 0.017), elevated AP50 (p = 0.023), decreased CFH (p = 0.005) and increased age (p = 0.041) were found to be independent risk factors for the development of hypertensive renal damage in healthy participants.
UNASSIGNED: Abnormal activation of complement, particularly complement AP, may be a risk factor for the development and progression of hypertensive renal damage.

C3 glomerulonephritis (C3GN) is a recently described form of GN that mainly occurs in children and young adults. It results from dysregulation of the alternative complement pathway. Studies have shown that dense deposit disease has a high recurrence rate; however, since C3GN is a recently described disorder, its recurrence rate is still variable. A 28-year-old male with end-stage renal disease caused by C3GN underwent renal transplantation. After 19 months, the patient experienced recurrent C3GN (rC3GN) that involved a variant of unknown significance in the ADAMTS13 gene. Over a short span of time, the patient suffered from rapid deterioration of the graft function that required renal replacement therapy. This is the first case of rC3GN that possibly involved genetic alteration, a variant within the ADAMTS 13 gene.

Complement-mediated kidney disease has been an evolving area in the field of nephrology. Atypical haemolytic uraemic syndrome (aHUS) is a rare thrombotic microangiopathy that affects multiple organs, particularly kidneys. The disease is characterised by a triad of haemolytic anaemia, thrombocytopenia and acute kidney injury (AKI). aHUS is most commonly caused by dysregulation of alternative complement pathway. In contrast to shiga toxin-associated haemolytic uraemic syndrome, diarrheal prodrome is usually absent in children with aHUS. We report a 2-year, 9-month-old boy who presented with acute dysentery and AKI. He had an unusual prolonged course of illness with hypocomplementaemia; hence, genetic testing was performed. He had a storming course in the hospital and succumbed to complications of the disease. Genetic study revealed digenic mutation in Complement Factor I and C3 Therefore, it is important to differentiate aHUS from other thrombotic microangiopathies to improve the outcome.

C3 Glomerulonephritis (C3GN) is a rare disease with an estimated incidence of 1-2 cases per million, caused by an alteration in the alternative complement pathway, although its complete physiopathology remains uncertain. Treatment evidence is poor. Immunosuppressive therapy can be initiated in more severe cases. Progression rates to end stage kidney disease are of up to 50% within a decade, and the posttransplant recurrence rates of 45-60%. We describe the case of a young man without any past medical history, with lower extremities edema, dyspnea, and kidney function deterioration. The patient was ultimately diagnosed with C3GN.

C3 glomerulopathy (C3G), a form of glomerulonephritis associated with dysregulation of the alternative complement pathway, occurs either as dense deposit disease (DDD) or C3 glomerulonephritis (C3GN). Few studies have reported outcomes of patients with C3G after transplantation since its formal classification and the advent of complement-targeting therapies such as eculizumab.
Case series of C3G.
We reviewed laboratory testing, native and allograft biopsy reports, and clinical charts of the 19 patients (12, C3GN; and 7, DDD) from our C3G registry who underwent transplantation between 1999 and 2016.
During a median follow-up of 76 months, 16 patients had recurrent disease (10 of 12, C3GN; and 6 of 7, DDD), with median time to recurrence of 14 months in C3GN versus 15 months in DDD. Graft failure was more frequent in patients with DDD (6 of 7) than in patients with C3GN (3 of 12), occurred at a median time of 42 months posttransplantation, and was attributed to recurrent disease in half the failures. A rare genetic variant or autoantibody associated with alternative complement pathway abnormalities was detected in 9 of 10 screened patients. Treatment of 7 patients (8 allografts) with eculizumab was associated with variable clinical outcomes.
Incomplete testing for complement pathway abnormalities and genetic defects, incomplete records of HLA antigen matching, lack of centralized biopsy review, and limited sample size.
In a case series of C3G transplant recipients, the proportion of disease recurrence was high in both C3GN and DDD, although graft loss appeared to occur more frequently in DDD. In a small subset of study patients, eculizumab therapy was not consistently followed by salutary outcomes.

The role of the complement system in first-time pathologic first-trimester miscarriage was investigated. In this case-control study, tissue samples of 126 women with pathologic miscarriage and termination of normal pregnancies were assessed. The pathologic pregnancy group consisted of 40 women with missed miscarriage, 13 women with incomplete miscarriage and 10 women with a blighted ovum. The control group consisted of 63 normal-appearing pregnancies. Immunoreactivity for C4d, Bb and MBL was evaluated in the deciduas and villous trophoblasts separately using a semi-quantitative histological scoring system (H-score). C4d and Bb H-scores were higher and MBL H-score was reduced in the deciduas and villous tissues from pathologic miscarriage compared to termination of pregnancies (p = .003 and p = .001; p = .011 and p < .001; p < .001 and p < .001, respectively). C4d and Bb activities were increased and MBL activity was decreased in human first-time pathologic first-trimester miscarriage. We suggest that three complement pathways may play a role in human first-time pathologic first-trimester miscarriage. Impact statement Previous studies focussed on complement proteins related to a single complement pathway in cases often associated with antiphospholipid syndrome (APS) or recurrent miscarriage. In APS-related cases, the classical pathway is activated. In antibody-dependent and in antibody-independent mouse models of foetal loss, classical and alternative pathways are activated, respectively. Lectin pathway deficiency has been reported in some recurrent miscarriage. The complement pathway or pathways, which have a role in human pathologic miscarriage was the starting point of this study. There has been no study done till now reporting the role of the three complement pathways in human pathologic miscarriage. In this study, we found increased classical and alternative complement pathway activities and decreased lectin pathway activity in tissues from first-time pathologic human miscarriage.

BACKGROUND: C3 glomerulonephritis (C3GN) and complement-mediated hemolytic uremic syndrome (HUS) both result from the abnormal regulation of the complement system. A significant number of patients with C3GN or complement-mediated HUS have mutations of more than 1 complement protein. This discovery has had a major impact on identifying the underlying cause of familial C3GN or complement-mediated HUS.
UNASSIGNED: We report the cases of 2 brothers (herein referred to as patient II-1 and patient II-9), both with complement disorders that differed in their clinical and genetic features.
UNASSIGNED: Patient II-1 clinically presented with nephrotic syndrome and acute kidney injury and pathologically presented with C3GN combined with thrombotic microangiopathy (TMA) and subacute tubulointerstitial nephritis. Meanwhile, patient II-9 clinically presented with HUS and pathologically presented with TMA combined with acute severe tubular injury.
METHODS: Screenings for genetic mutations contributed to complement system dysregulation were performed on patient II-1.
RESULTS: The genome sequencing identified that patient II-1 had a heterozygous mutation in the C3 gene (c.C1774T/p.R592W). Nine other relatives of the brothers were checked for this C3 mutation and only the daughter of patient II-1 (herein referred to as patient III-2) carried it, but so far, she does not have any clinical manifestations of kidney disease.
UNASSIGNED: Family members with a dysregulation of the complement alternative pathway may differ in its clinical and genetic features.

Dysfunction of the alternative pathway of complement activation provides a pathophysiologic link between the C3 glomerulopathies dense deposit disease and glomerulonephritis with C3 deposition and the clinically and histologically distinct atypical hemolytic uremic syndrome. Previously, dense deposit disease was known as membranoproliferative glomerulonephritis type II, but paucity or complete lack of immunoglobulin deposition on immunofluorescence staining and advances in our understanding of alternative pathway dysregulation have separated it from immune complex-mediated membranoproliferative glomerulonephritis types I and III. We discuss a case of dense deposit disease and review the current pathologic classification, clinical course, treatment options, and related conditions.

Cystic fibrosis (CF) is perceived as a childhood illness. However, with advances in medical science, patients are enjoying lives extending well into adulthood. This article reviews two cases of membranoproliferative glomerulonephritis (MPGN) in adults with CF. One patient with severe CF pulmonary disease had concomitant renal failure during hospitalization for a pulmonary exacerbation. Subsequent evaluations, including complement levels, were consistent with MPGN. The second patient had been recently diagnosed with colon cancer and was found to be suffering from acute renal failure. Diagnostic evaluation likewise confirmed the MPGN diagnosis. Immunologic associations linking CF and MPGN, including derangements in the complement system and the effects of superantigen production, are reviewed.

A 40-year-old female patient has been suffering from localized heat urticaria for 8 years and, in addition, from localized cold urticaria for 1 year. Both diseases could be proved by adequate physical tests. Exposition to localized heat provoked decreased serum complement, suggesting activation of the alternative pathway.