Hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli in a renal transplant recipient case report / Síndrome hemolítico-urêmica causada por Escherichia coli produtora de toxina Shiga em um relato de caso de receptor de transplante renal

Abstract Thrombotic microangiopathies are disorders characterized by nonimmune microangiopathic hemolytic anemia, thrombocytopenia, and multi-systemic failure. They are classified as thrombotic thrombocytopenic purpura, atypical hemolytic-uremic syndrome, and typical hemolytic uremic syndrome. The latter is associated with intestinal infections by Shiga toxin-producing bacteria. Typical hemolytic uremic syndrome in adults is an extremely rare condition, characterized by high morbidity and mortality. It has been seldom described in solid organ transplant recipients. Here is presented the case of a kidney transplant recipient who had typical hemolytic uremic syndrome with multisystem commitment, refractory to management and with a fatal outcome.

Resumo Microangiopatias trombóticas são distúrbios caracterizados por anemia hemolítica microangiopática não imune, trombocitopenia e insuficiência multissistêmica. Elas são classificadas como púrpura trombocitopênica trombótica, síndrome hemolítico-urêmica atípica e síndrome urêmica hemolítica típica. Essa última está associada a infecções intestinais por bactérias produtoras da toxina Shiga. A síndrome hemolítica urêmica típica em adultos é uma condição extremamente rara, caracterizada por alta morbimortalidade. Esta é raramente descrita em receptores de transplantes de órgãos sólidos. Apresentamos aqui o caso de um receptor de transplante renal que apresentava síndrome hemolítico-urêmica típica com comprometimento multissistêmico, refratário ao tratamento, e com desfecho fatal.

Síndrome hemolítico urémico asociado a toxina Shiga con hipocomplementemia en edad atípica. Caso clínico

The Shiga toxin associated (Stx) hemolytic uremic syndrome (HUS) is an important cause of acute renal failure (ARF) and the most common cause of thrombotic microangiopathy (TMA) in pediatrics. Primary atypical HUS (aHUS) is a rare disease due to a genetic defect in the alternative complement pathway. Both diseases may share clinical and laboratory elements, making differential diagnosis difficult, such as the presence of diarrhea in aHUS or complement alterations in HUS-Stx. The treatment and prognosis of both diseases is completely different. We report a 15-year-old male with severe HUS. After a self-limited diarrheal syndrome, he had a severe TMA and ARF, requiring renal replacement therapy. An extensive etiological study was carried out, ruling out the main causes of TMA. Alterations in complement factors were observed. Finally, the diagnosis of HUS-Stx was established. The patient evolved favorably with recovery of renal function.

Role of alternative complement pathway overactivation in malignant nephrosclerosis / 中华肾脏病杂志

Objective To study the role of alternative complement pathway overactivation in malignant nephrosclerosis.Methods (1) Fifty patients with confirmed malignant nephrosclerosis by renal needle biopsy were enrolled.Meanwhile,twenty-five cases of time-zero renal needle biopsy were enrolled as control subjects.Enzyme linked immunosorbent assay (ELISA) was used to detect alternative complement pathway of the complement initiation factor B,positive regulation factor P,negative regulation factor H,and the complement end products C3a and C5a in the plasma and urine.(2) Immunohistochemistry was used to detect the deposition of the complement end product C5b-9,C4d and mannan binding lectin (MBL) of lectin pathway in the renal biopsies.Double immunofluorescence labeling method was used to assay the deposition of C5b-9 and CD34 (endothelial cell marker) in the arteriolar endothelium and glomerular capillary endothelium.Results (1) The plasma and urine levels of complement factor B,factor P,C3a and C5a in malignant nephrosclerosis patients were significantly higher than those in control subjects (all P ＜ 0.05),while the plasma and urine levels of complement factor H in malignant nephrosclerosis patients were lower than those in control subjects (all P ＜ 0.05).(2) The plasma level of factor P was positively correlated with 24 h urine protein (rs=0.465,P=0.001).Urinary factor B/urinary creatinine,urinary factor P/urinary creatinine and urinary C3a/urinary creatinine were positively correlated with serum creatinine in malignant nephrosclerosis patients (rs=0.483,P ＜ 0.001;rs=0.352,P=0.012;rs=0.319,P=0.024),while urinary factor H/urinary creatinine was negatively correlated with serum creatinine and 24 h urine protein (rs=-0.299,P=0.035;rs=-0.342,P=0.015).Urinary C5a/urinary creatinine was positively correlated with serum creatinine and 24 h urine protein (rs=0.525,P ＜ 0.001;rs=0.496,P ＜ 0.001).(3) Immunohistochemical results showed that there were C5b-9 deposited in the arterioles and glomerular capillary wall in malignant nephrosclerosis patients,and no deposition in control renal tissues.Meanwhile,the semi-quantitative scores showed that C5b-9 deposition intensity was positively correlated with serum creatinine and 24 h urine protein (rs=0.791,P＜ 0.001;rs=0.345,P=0.014).The double immunofluorescence labeling analysis showed that the C5b-9 and CD34 deposited in the arteriolar endothelium and glomerular capillary endothelium.(4) Plasma level of factor B in malignant nephrosclerosis patients was positively correlated with plasma C3a level (r=0.331,P=0.022).Plasma level of factor P was positively correlated with C5b-9 score (rs=0.300,P=0.034).Urinary B was positively correlated with urinary C3a,C5a and C5b-9 score (rs=0.311,P=0.028;rs=0.465,P=0.001;rs=0.428,P=0.002).Urinary factor P was also positively correlated with urinary C3a and C5a (rs=0.307,P=0.030;rs=0.442,P=0.001).Immunohistochemical result showed that there were C4d deposited in the arterioles and glomerular,and no deposition of MBL.Conclusion Complement activation via the alternative pathway may be involved in malignant nephrosclerosis and related to the severity of the disease.

Role of alternative complement pathway overactivation in malignant nephrosclerosis / 中华肾脏病杂志

Objective@#To study the role of alternative complement pathway overactivation in malignant nephrosclerosis.@*Methods@#(1) Fifty patients with confirmed malignant nephrosclerosis by renal needle biopsy were enrolled. Meanwhile, twenty-five cases of time-zero renal needle biopsy were enrolled as control subjects. Enzyme linked immunosorbent assay (ELISA) was used to detect alternative complement pathway of the complement initiation factor B, positive regulation factor P, negative regulation factor H, and the complement end products C3a and C5a in the plasma and urine. (2) Immunohistochemistry was used to detect the deposition of the complement end product C5b-9, C4d and mannan binding lectin (MBL) of lectin pathway in the renal biopsies. Double immunofluorescence labeling method was used to assay the deposition of C5b-9 and CD34 (endothelial cell marker) in the arteriolar endothelium and glomerular capillary endothelium.@*Results@#(1) The plasma and urine levels of complement factor B, factor P, C3a and C5a in malignant nephrosclerosis patients were significantly higher than those in control subjects (all P<0.05), while the plasma and urine levels of complement factor H in malignant nephrosclerosis patients were lower than those in control subjects (all P<0.05). (2) The plasma level of factor P was positively correlated with 24 h urine protein (rs=0.465, P=0.001). Urinary factor B/urinary creatinine, urinary factor P/urinary creatinine and urinary C3a/urinary creatinine were positively correlated with serum creatinine in malignant nephrosclerosis patients (rs=0.483, P<0.001; rs=0.352, P=0.012; rs=0.319, P=0.024), while urinary factor H/urinary creatinine was negatively correlated with serum creatinine and 24 h urine protein (rs=-0.299, P=0.035; rs=-0.342, P=0.015). Urinary C5a/urinary creatinine was positively correlated with serum creatinine and 24 h urine protein (rs=0.525, P<0.001; rs=0.496, P<0.001). (3) Immunohistochemical results showed that there were C5b-9 deposited in the arterioles and glomerular capillary wall in malignant nephrosclerosis patients, and no deposition in control renal tissues. Meanwhile, the semi-quantitative scores showed that C5b-9 deposition intensity was positively correlated with serum creatinine and 24 h urine protein (rs=0.791, P<0.001; rs=0.345, P=0.014). The double immunofluorescence labeling analysis showed that the C5b-9 and CD34 deposited in the arteriolar endothelium and glomerular capillary endothelium. (4) Plasma level of factor B in malignant nephrosclerosis patients was positively correlated with plasma C3a level (r=0.331, P=0.022). Plasma level of factor P was positively correlated with C5b-9 score (rs=0.300, P=0.034). Urinary B was positively correlated with urinary C3a, C5a and C5b-9 score (rs=0.311, P=0.028; rs=0.465, P=0.001; rs=0.428, P=0.002). Urinary factor P was also positively correlated with urinary C3a and C5a (rs=0.307, P=0.030; rs=0.442, P=0.001). Immunohistochemical result showed that there were C4d deposited in the arterioles and glomerular, and no deposition of MBL.@*Conclusion@#Complement activation via the alternative pathway may be involved in malignant nephrosclerosis and related to the severity of the disease.

The role of complement system in thrombotic microangiopathy and its research progress / 中华检验医学杂志

Thrombotic microangiopathy (TMA) is a group of acute clinical pathological syndromes with common pathological features, which include hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura syndrome. They have many similarities in etiology and clinical presentation. The role of abnormal activation of complement bypass pathway in the genesis and development of HUS has been recognized. More than 100 kinds of complement regulatory factors or gene mutations of complement itself were found to be associated with the development of HUS, which resulted in the decrease of negative complement regulatory protein activity or the increase of complement activation protein function. Abnormal activation of complement system resulted in endothelial injury and thrombosis. Loss of ADAMTS13 activity (<10%) is the most important pathogenesis of TTP. However, there are more and more evidence that complement bypassing pathway is over-regulated and over-activated in the formation of TTP. At present, the research of TMA is focused on finding specific complement-activated biomarkers in patients with various forms of TMA and developing new targeted therapeutic drugs for the disease.

The role of complement system in thrombotic microangiopathy and its research progress / 中华检验医学杂志

Thrombotic microangiopathy (TMA) is a group of acute clinical pathological syndromes with common pathological features, which include hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura syndrome. They have many similarities in etiology and clinical presentation. The role of abnormal activation of complement bypass pathway in the genesis and development of HUS has been recognized. More than 100 kinds of complement regulatory factors or gene mutations of complement itself were found to be associated with the development of HUS, which resulted in the decrease of negative complement regulatory protein activity or the increase of complement activation protein function . Abnormal activation of complement system resulted in endothelial injury and thrombosis. Loss of ADAMTS13 activity (<10％) is the most important pathogenesis of TTP. However, there are more and more evidence that complement bypassing pathway is over-regulated and over-activated in the formation of TTP. At present, the research of TMA is focused on finding specific complement-activated biomarkers in patients with various forms of TMA and developing new targeted therapeutic drugs for the disease.

Atypical Hemolytic Uremic Syndrome in a 13-year-old Lao Girl: A Case Report

Atypical hemolytic uremic syndrome (aHUS), a rare form of thrombotic microangiopathy, is distinguished from the typical form by the absence of a preceding verotoxin-producing Escherichia coli infection. Notably, aHUS occurs in association with genetic or acquired disorders causing dysregulation of the alternative complement pathway. Patients with aHUS may show the presence of anti-complement factor H (CFH) autoantibodies. This acquired form of aHUS (anti-CFH-aHUS) primarily affects children aged 9–13 years. We report a case of a 13-year-old Lao girl with clinical features of aHUS (most likely anti-CFH-aHUS). The initial presentation of the patient met the classical clinical triad of thrombotic microangiopathy (microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury) without preceding diarrheal illness. Low serum levels of complement 3 and normal levels of complement 4 indicated abnormal activation of the alternative complement pathway. Plasma infusion and high-dose corticosteroid therapy resulted in improvement of the renal function and hematological profile, although the patient subsequently died of infectious complications. This is the first case report that describes aHUS (possibly anti-CFH-aHUS) in Laos.

Pathology of C3 Glomerulopathy

C3 glomerulopathy is a renal disorder involving dysregulation of alternative pathway complement activation. In most instances, a membranoproliferative pattern of glomerular injury with a prevalence of C3 deposition is observed by immunofluorescence microscopy. Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are subclasses of C3 glomerulopathy that are distinguishable by electron microscopy. Highly electron-dense transformation of glomerular basement membrane is characteristic of DDD. C3GN should be differentiated from post-infectious glomerulonephritis and other immune complex-mediated glomerulonephritides showing C3 deposits.

Síndrome hemolítico urémico atípico: papel del perfil genético / Atypical hemolytic uremic syndrome: role of the genetic profile

Resumen: El síndrome hemolítico urémico es una microangiopatía trombótica caracterizada por anemia hemolítica microangiopática, trombocitopenia y daño renal agudo. El síndrome hemolítico urémico típico (el más común) es ocasionado por bacterias productoras de la toxina Shiga, típicamente por cepas de Escherichia coli. El término síndrome hemolítico urémico atípico se usa para referirse a los pacientes que padecen este cuadro por causas diferentes. Las manifestaciones clínicas y paraclínicas no son suficientes para diferenciar el síndrome hemolítico urémico atípico de otras microangiopatías trombóticas, por lo que la determinación de la actividad de ADAMTS13 y la prueba de la toxina Shiga resultan esenciales para establecer el diagnóstico preciso. Aunque en la actualidad el diagnóstico definitivo requiere confirmación genética, las pruebas genéticas son costosas y poco útiles para el diagnóstico inicial; sin embargo, más que importancia diagnóstica, tiene gran valor pronóstico, permite prescribir el tratamiento adecuado disminuyendo significativamente la morbilidad y mortalidad atribuibles a esta enfermedad.

Abstract: The haemolytic uraemic syndrome is a thrombotic microangiopathy (TMA) characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal injury. The typical haemolytic uraemic syndrome (tHUS, the most common) is caused by bacteria that produce Shiga toxin, typically strains of Escherichia coli. On the other hand, the term atypical haemolytic uraemic syndrome (aHUS) is used to refer to those patients who develop this condition due to different etiologies. The clinical and paraclinical manifestations are not enough to differentiate the aHUS from other thrombotic microangiopathies, so the determination of the activity of ADAMTS13 and the Shiga toxin test are essential to establish the precise diagnosis. Although currently the diagnosis requires genetic confirmation, the genetic tests are expensive and not very useful for the initial diagnosis; however, more than diagnostic importance, it has a great prognostic value allowing establishing an adequate management and significantly reducing the morbidity and mortality attributable to this condition.

Analysis of variants in complement genes in Han Chinese children with atypical hemolytic uremic syndrome / 中华儿科杂志

Objective@#To investigate the prevalence and characteristics of pathogenic variants in complement genes in Han Chinese children with atypical hemolytic uremic syndrome (aHUS).@*Method@#Eleven Han Chinese children with aHUS, including 9 boys and 2 girls aged between 1 year and 4 months and 13 years, were investigated in Department of Pediatrics, Fuzhou General Hospital, from November 1998 to February 2014. Analysis of variants of all the exons of 10 complement genes (CFH, MCP, CFI, C3, CFB, CFHR1, CFHR2, CFHR3, CFHR4 and CFHR5), including 25 bases from 3′ end and 25 bases from 5' end, was performed in the 11 cases by targeted sequence capture and next generation sequencing. Significant variants detected by next generation sequencing were confirmed by Sanger sequencing. To understand pathogenicity of variants found in the captured genes, we investigated genetic conservation by multiple protein sequence alignment among different species, and analyzed whether the variants were located in protein domains or not, and investigated functional significance by functional computational prediction methods.@*Result@#Twenty-seven percent of Han Chinese children with aHUS carried pathogenic variants in the 10 complement genes. Pathogenic variant CFB 221G>A (R74H) was detected in Patient 3 and Patient 9, which was not found in parents of Patient 3′ , and was found in healthy father of patient 9. Pathogenic variant CFHR5 242C>T (P81L) was found in Patient 2, and was found in healthy father of patient 2. However, no pathogenic variants in genes CFH, MCP, CFI, C3, CFHR1, CFHR2, CFHR3 and CFHR4 were identified.@*Conclusion@#Pathogenic variants in the 10 complement genes were identified in 3/11 of Han Chinese children with aHUS in our study and CFB was the most frequently mutated gene.

Inflammatory mechanism of acute lung injury in mice induced by activation of complement alternative pathway / 中国药理学通报

Aim To study the development of acute lung inflammation in mice induced by activation of the complement alternative pathway and the changes of the related indicators, and to provide an ideal pathological model of acute lung inflammation in mice for drug screening and intervention. Methods Cobra venom factor( CVF) was used to activate complement alterna-tive pathway of SPF Kunming mice by intravenous injection. According to different sampling time, the mice were divided into 15 min, 30 min, 1 h, 2 h, 6 h group, and the parallel PBS control groups were set at the same time. Lung coefficient, lung water content, myeloperoxidase ( MPO ) activity, BALF cell number and protein content were tested. The pathological changes of lung tissue were observed by HE staining. The concentration of IL-6 , TNF-α, P-selectin and ICAM-1 in bronchoalveolar lavage fluid ( BALF ) and serum were determined by ELISA. Results CVF caused pulmonary inflammatory cell infiltration in mice obviously. Compared with PBS groups, MPO activity of lung tissue, BALF cell and the protein concentration were significantly increased. The contents of IL-6, TNF-α, P-selectin in BALF and serum were in-creased, and the content of ICAM-1 in serum was also increased. The content of P-selectin in BALF reached the first peak at 30 min point, the content of IL-6 and TNF-α in BALF reached the first peak at 1 h point, but the indicators had no further changes at 2 h point, and all the indicators rose again at 6 h point. The lev-els of IL-6 and TNF-α in serum reached peak at 1 h point,then the content showed lower levels at the sub-sequent time points. The levels of P-selectin and ICAM-1 in serum increased along the time. Lung coef-ficient, lung water content and ICAM-1 of the BALF showed no significant alteration. Conclusion The ac-tivation of the complement alternative pathway can lead to acute lung inflammation in mice and the inflammato-ry response is the most obvious at 30 min to 1 h. The study could provide an ideal pathological model of a-cute lung inflammation in mice for drug screening and intervention.

Activation of serum complement in Posner-Schlossman syndrome patients / 中华实验眼科杂志

Background Activation of serum complement system is involved in the pathological process of uveitis and open angle glaucoma.Pathogenesis and pathological characteristics of Posner-Schlossman syndrome (PSS) are similar to uveitis and open angle glaucoma.However,etiology of PSS remains unelucidated.The activation complement in PSS patients' serum is rarely reported.Objective The aim of this study was to investigate the activation of serum complement in PSS patients for PSS pathogenesis.Methods A prospective case-controlled study was designed.The peripheral blood simples of 79 PSS patients were collected from Shenzhen Eye Hospital during December 2013 to December 2015,and the peripheral blood simples were obtained from 83 unrelated healthy blood donors as healthy control group.Immuno-scatter turbidmetry was adopted to detect the common activated components in complement pathway in each group including complement C3 (a vital intersection molecule in the three pathways),C4 (the vital molecule both the complement classical and lectin pathways),split products C3a,soluble membrane attack complex (sC5b-9),C 1q (complement classical pathway),L-ficolin (complement lectin pathway),complement factor Bb (complement alternative pathway),IgG,IgA and IgM.The correlation between serum C3a content and sC5b-9 content in PSS group was analyzed.The serum contents of fabric binding protein 2 (FCN2) (a marker of serum classical pathway),factor Bb (a marker of complement alternative pathway),C3a (the common activation products of three complement activation pathways),and sC5b-9 were assayed by ELISA.This research protocal was approved by Shenzhen Eye Hospital and written informed consent was obtained from each PSS patient prior to any medical examination.Results Compared with normal control group,the serum levels of C3,C4,C3a,sC5b-9,C1q,FCN2,IgG,IgA and IgM were significantly higher in PSS group (Z =-4.743,-2.913,-1.985,-2.620,-2.062,-2.500,-7.010,-6.327,-3.652,all at P ＜ 0.05).The serum complement factor Bb level was 13.87 (9.24,32.00) μg/ml in PSS group,which was significantly lower than 20.51 (12.90,33.50) μg/ml in normal control group (Z =-2.515,P =0.012).Serum C3a content was positively correlated with the serum sC5b-9 content in PSS group (rs =0.832,P＜0.001).Conclusions The serum complement system is activated in PSS patients.Complement alternative pathway,classical pathway and lectin pathway might all be involved in the activative process of complement system.

Glomerulonefritis C3: una nueva categoría de glomerulonefritis con implicaciones etiopatogénicas / C3 glomerulonephritis: a new category of glomerulonephritis with etiopathogenic implications / Glomerulonefrite C3: uma nova categoria de glomerulonefrite com envolvimentos etiopatogênicas

Introducción: las glomerulonefritis con depósitos exclusivos de la fracción C3 del complemento (GN-C3) pueden implicar alteración en la vía alterna de este. Objetivos: describir retrospectivamente una serie de casos de GN-C3 y determinar la frecuencia con que los pacientes continúan con alteraciones renales y/o hipocomplementemia. Métodos: se evaluaron las características histológicas y clínicas y la evolución de los 22 casos de GN-C3 diagnosticados entre 2004 y 2012 en el Departamento de Patología (Facultad de Medicina, Universidad de Antioquia). Resultados: 14 de los pacientes fueron niños y 12 fueron hombres; la mediana de edad fue de 13 años (rango: 3-65). Diez se presentaron como síndrome nefrítico, siete como GN rápidamente progresiva, tres como insuficiencia renal aguda, uno como insuficiencia renal crónica y uno como síndrome nefrótico-nefrítico; 21 tenían hipocomplementemia C3. Todas las biopsias mostraron GN proliferativa. Ocho pacientes tuvieron remisión completa; cuatro, alteraciones persistentes del uroanálisis; seis desarrollaron enfermedad renal crónica, en cinco de ellos terminal; en cuatro no hubo seguimiento. En nueve pacientes hubo seguimiento de los niveles séricos de C3 y en todos ellos se normalizaron entre 1 y 3 meses después de la biopsia. Conclusiones: las GN-C3 pueden producir alteraciones renales persistentes o recurrentes y evolucionar a la insuficiencia renal terminal. Es recomendable el seguimiento clínico a largo plazo, con mediciones repetidas de los niveles de C3.

Introduction: Glomerulonephritis with only deposits of C3 (GN-C3) could involve alteration on the complement alternative pathway. Objective: To describe retrospectively a series of GNC3 cases and to determine the frequency with which patients continue with renal alterations and/or hypocomplementemia. Methods: The 22 cases of GN-C3 diagnosed between 2004 and 2012 at the Department of Pathology, Faculty of Medicine, University of Antioquia (Medellin, Colombia) were included. Their histological and clinical characteristics and their outcome were evaluated. Results: 14 patients were children and 12 were males. Mean age was 13 years (range: 3-65). Ten presented as a nephritic syndrome, seven as a rapidly progressive GN, three as acute renal failure, one as chronic renal failure, and one as a nephrotic-nephritic syndrome. The C3 fraction of complement was low in 21 cases. All biopsies showed proliferative GN. There was complete remission in eight patients, persistent urinalysis alterations in four, chronic renal failure in six, five of them end-stage. No follow-up was done in four. In nine patients follow-up determination of C3 serum levels was done; in all of them they normalized between 1 to 3 months after biopsy. Conclusions: GN-C3 can produce persistent or recurrent kidney alterations and end-stage renal disease. Long-term follow-up with repeated determinations of C3 is advisable.

Introdução: as glomerulonefrite com depósitos exclusivos da fração C3 do complemento (GN-C3) podem implicar alteração na via alterna deste. Objetivos: descrever retrospectivamente uma série de casos de GN-C3 e determinar a frequência com que os pacientes continuam com alterações renais e/ ou hipocomplementemia. Métodos: avaliaram-se as características histológicas e clínicas e a evolução dos 22 casos de GN-C3 diagnosticados entre 2004 e 2012 no Departamento de Patologia (Faculdade de Medicina, Universidade de Antioquia). Resultados: 14 dos pacientes foram meninos e 12 foram homens; a média de idade foi de 13 anos (casta: 3-65). Dez se apresentaram como síndrome nefrítico, sete como GN rapidamente progressiva, três como insuficiência renal aguda, um como insuficiência renal crônica e um como síndrome nefrótico-nefrítico; 21 tinham hipocomplementemia C3. Todas as biopsias mostraram GN proliferativa. Oito pacientes tiveram remissão completa; quatro, alterações persistentes do uroanálise; seis desenvolveram doença renal crônica, em cinco deles terminal; em quatro não teve seguimento. Em nove pacientes teve seguimento dos níveis séricos de C3 e em todos eles se normalizaram entre 1 e 3 meses depois da biopsia. Conclusões: as GN-C3 podem produzir alterações renais persistentes.

Pathology of C3 Glomerulonephritis

C3 glomerulonephritis (C3GN) is a recently described entity that shows a glomerulonephritis on light microscopy, bright C3 staining and the absence of C1q, C4, and immunoglobulins on immunofluorescence microscopy and mesangial and/or subendothelial electron-dense deposits on electron microscopy. The term 'C3 glomerulopathy' is often used to include C3GN and dense deposit disease (DDD), CFHR5 nephropathy, those of which result from dysregulation of the alternative pathway of complement. C3GN shares some aspects of atypical hemolytic uremic syndrome, MPGN, late stage of post infectious glomerulonephritis and other glomerulonephrtis. When C3GN is considered, measurement of serum complement proteins including C3, CFH, CFI, CFB and testing for the presence of C3 nephritic factor, anti-factor H autoantibodies are necessary. To screening for mutations, genes that encode complement regulators should be evaluated. This disorder equally affected all ages, both genders, and typically presented with hematuria and proteinuria. In both the short and long term, renal function remained stable in the majority of patients.

Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32 percent) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production.

Activation of CD40-CD154 co-stimulatory pathway and its correlation with disease activity in patients with inflammatory bowel disease / 中华消化内镜杂志

Objective To investigate the expression of CD40-CD154 co-stimulatory pathway in peripheral circulation and intestinal mucosa in patients with inflammatory bowel disease (IBD),the difference between the expression of CD40-CD154 in patients with IBD and that in healthy controls,and the correlation between CD40-CD154 levels and disease activity. Methods A total of 62 patients with Crohn's disease (CD),64 patients with ulcerative colitis (UC) and 56 healthy controls were enrolled. Enzyme-Linked Immuno Sorbent Assay (ELISA),SYBR-green real time PCR and immunohistochemical assay were respectively applied to evaluate expression of CD40-CD154 in plasma,mononuclear cells of peripheral blood and intestinal mucosa. Results Levels of CD40 (P=0. 000) and CD154 (P=0. 001) in plasma,mononuclear cells of peripheral blood and intestinal mucosa were significantly higher in patients with CD and UC than in healthy controls. However,no correlation between disease activity and CD40-CD154 expression in peripheral circulation or intestinal mucosa was detected (P ＞ 0. 05 ). Conclusion CD40-CD154 pathway activation is found in plasma,peripheral blood mononuclear cells and intestinal mucosa in patients with IBD,but is not correlated with disease activity.

Alteraciones del sistema complemento en pacientes con anemia drepanocítica en estado basal / Alterations of the complement system in patients with basal sickle cell anemia

Se determinó la actividad de las vías clásica y alternativa del complemento, así como la cuantificación de algunos de sus componentes en 46 pacientes con anemia drepanocítica (AD) (hemoglobina SS), 21 sin complicaciones clínicas y 25 con estas; entre las más frecuentes encontramos: número de infecciones, úlceras maleolares, crisis vasooclusivas, hepáticas y aplásticas, considerando como límite un año anterior a la toma de muestra de sangre. Se demostró una disminución significativa de la actividad de la vía alternativa, factor B y del componente C3 en el grupo de pacientes con complicaciones clínicas. Se observó una correlación significativa entre el número de crisis vasooclusivas e infecciones y la actividad de la vía alternativa, el factor B y el C3. Estos resultados sugieren que los fenómenos inflamatorios que pueden persistir en pacientes con AD en estado basal, fundamentalmente aquellos con historia anterior de complicaciones clínicas, pueden provocar alteraciones en la actividad del complemento.

The activity of the classic and alternative complement pathways, as well as the quantitation of some of their components was determined in 46 patients with sickle cell anemia (haemoglobin SS), 21 with no clinical complications and 25 with them. Among the most frequent complications we found: number of infections, malleolar ulcers, and vaso-occlusive, hepatic and aplastic crises. A year previous to the blood sample taking was considered as the limit. A significant reduction of the activity of the alternative pathway, factor B and component C3 was proved in the group of patients with clinical complications. A marked correlation was observed between the number of vaso-occlusive crises and infections and the activity of the alternative pathway, factor B and complement C3. These results suggest that the inflammatory phenomena that may persist among patients with basal sickle cell anemia, mainly those with prior history of clinical complications, may produce alterations in the complement activity.