Clinical characteristics and prognosis of anti-factor H antibody associated-atypical hemolytic uremic syndrome in children / 中华实用儿科临床杂志

Objective:To summarize the clinical data of anti-factor H antibody-associated atypical hemolytic uremic syndrome (aHUS) in children, and analyze the risk factors for disease recurrence and poor prognosis.Methods:A prospective cohort study was conducted on 52 children with anti-factor H antibody-associated aHUS in Beijing Children′s Hospital, Capital Medical University from November 2011 to November 2021.Patient information about the genetic background, clinical and renal pathological characteristics, treatment, and prognosis were collected.Then, the disease recurrence and prognosis were analyzed using the survival curve and Cox regression model. Results:In 52 children, there were 33 males and 19 females.The average age of onset for aHUS was 2.4-12.8 years, and 92.3%(48/52) of the children developed symptoms at the age of 4-12 years.The copy numbers of complement factor-H-related 1 (CFHR1) and complement factor-H-related 3 (CFHR3) genes were calculated in 42 children.Among the 42 cases, 18 cases (42.9%) had CFHR1 homozygous deletion, and 83.3% (15/18) of them also had CFHR3 homozygous deletion.All the patients were given plasma therapy.Besides, 76.9% (40/52) of the children were treated with immunosuppressive therapy (steroid and/or immunosuppressant) at the first onset of the disease.About 86.5%(45/52 cases) of the patients received immunosuppressive therapy in the course of disease, and the immunosuppressive treatment lasted for 6-20 months in total.The median follow-up time was 58 (28, 91) months.Among 52 patients, only 12 patients (23.1%) suffered disease recurrence.The relapse-free survival rate in children with CFHR1 homozygous deletion was significantly lower than that in children with non-homozygous deletion ( χ2=4.700, P=0.030). The relapse-free survival rate in children with CFHR1 and CFHR3 homozygous deletions was also significantly lower than that in other children ( χ2=4.181, P=0.041). At the end of the follow-up, 73.1%(38/52) of the children had normal renal function and no persistent proteinuria or hypertension.23.1%(12/52 cases) of the children had persistent proteinuria and/or hypertension.One child had Stage 3-4 chronic kidney disease, and 1 child was dialysis dependent. Conclusions:Anti-factor H antibody-associated aHUS is prone to occur in children aged between 4-12 years old, who respond well to plasma therapy and immunosuppressive therapy.Children with anti-factor H antibody-associated aHUS and CFHR1 and CFHR3 homozygous deletions have a high recurrence rate.Treatment with immunosuppressive therapy and assessment of the copy number of CFHR1 and CFHR3 genes in the early stage of the disease are important for preventing disease recurrence and improving prognosis.

Complement factor H levels are decreased and correlated with serum C-reactive protein in late-onset Alzheimer's disease / Os níveis de fator H do complemento estão diminuídos e correlacionados com a proteína C-reativa sérica na doença de Alzheimer de início tardio

Abstract Alzheimer's disease (AD) is the most common cause of dementia. Despite numerous studies on the subject, the pathologies for AD are still unclear and there is still no ideal biomarker for diagnosis. The present study aimed to investigate clinical significance of human complement factor H (CFH) in patients with late-onset AD. Methods: The present prospective study included 187 late-onset AD patients who went to our hospital from January 2015 to December 2017. One hundred patients with mild cognitive impairment (MCI) and 80 healthy individuals who were age and gender matched to AD patients were enrolled as controls. Demographic data such as age, gender, and education duration were recorded. Blood samples were collected and serum levels of C-reactive protein (CRP), CFH, and brain-derived neurotrophic factor (BDNF) were determined by Enzyme-linked immunosorbent assay (ELISA). The mini-mental state examination (MMSE) score was measured for all patients. Results: No significant difference was found in age, gender, and education duration for all participants. The MMSE scores showed AD patients had lower MMES scores than the other two groups. All factors of CFH, CRP, and BDNF were dramatically decreased in AD patients compared with the MCI and the ealthy control. Levels of CFH were found to be positively correlated with levels of CRP; however, no significant correlation was found between CFH and BDNF, nor CFH and MMSE. Conclusion: CFH was decreased in late-onset AD patients, and serum levels of CFH was correlated with serum levels of CRP, but not MMSE and BDNF. These results may provide more clinical evidences for the role of CFH in AD patients.

Resumo A doença de Alzheimer (DA) é a causa mais comum de demência. Apesar de inúmeros estudos sobre DA, suas patologias ainda não são claras e ainda não existe um biomarcador ideal para o diagnóstico da condição. O presente estudo teve como objetivo investigar a significância clínica do fator H do complemento humano (CFH) em pacientes com DA de início tardio. Métodos: O presente estudo prospectivo incluiu um total de 187 pacientes com DA de início tardio que foram ao nosso hospital entre janeiro de 2015 e dezembro de 2017. Cem pacientes com comprometimento cognitivo leve (CCL) e 80 indivíduos saudáveis com idade e sexo pareados com pacientes com DA foram incluídos como controle. Dados demográficos como idade, sexo e duração da educação foram registrados. As amostras de sangue foram coletadas e os níveis séricos de proteína C-reativa (PCR), CFH e fator neurotrófico derivado do cérebro (BDNF) foram determinados pelo ensaio imunoabsorvente ligado à enzima (ELISA). O escore do miniexame do estado mental (MEEM) foi medido para todos os pacientes. Resultados: Não foram encontradas diferenças significativas em idade, sexo e duração da educação para todos os participantes. Pacientes com DA tinham os menores escores de MEEM em relação aos outros dois grupos. Todos os fatores de CFH, PCR e BDNF diminuíram drasticamente em pacientes com DA em comparação com o CCL e o controle saudável. Os níveis de CFH mostraram correlação positiva com os níveis de PCR; no entanto, não foi encontrada correlação significativa entre CFH e BDNF, nem CFH e MEEM. Conclusão: A CFH diminuiu nos pacientes com DA de início tardio e os níveis séricos de CFH foram correlacionados com os níveis séricos de PCR, mas não o MEEM e o BDNF. Esses resultados podem fornecer mais evidências clínicas do papel da CFH em pacientes com DA.

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.

Analysis of 66 children with atypical hemolytic uremic syndrome / 中华肾脏病杂志

Objective To summarize the clinical data of atypical hemolytic uremic syndrome (aHUS) and analyze the treatment and prognosis.Methods A prospective cohort study was conducted on 66 cases in Beijing Children's Hospital affiliated to Capital Medical University from January 2011 to December 2017.The children were divided into positive and negative auto-antibody groups according to the results of anti-factor H autoantibody test.The clinical characteristics,treatment plan and prognosis of the two groups were compared.Results Among the 66 children who met the inclusion criteria,there were 43 cases (65.2％) in the positive group,with an average onset age of (8.0±2.9) years.There were 23 eases (34.8％) in the negative group,with an average onset age of (3.0± 2.6) years.On the basis of plasma treatment,in the positive group,the usage rate of hormone was 83.3％ (35/42) and the usage rate of immunosuppressive agents was 42.9％(18/42),while in the negative group,the rates were 63.6％(14/22) and 13.6％(3/22) respectively.The average follow-up time was 19.3 months.One child in each group was lost to follow-up.In the positive group,8 cases recurred (19.0％)and the average recurrence interval time was 16.1 months.In the negative group,7 cases recurred (31.8％) and the average recurrence interval time was 9.3 months.And the recurrent interval time in the positive group was more longer than the negative group (P ＜ 0.05).A total of 85.9％(55/64) children had complete hemolysis control and complete recovery of renal function,in which the positive group was 85.7％(36/42) and negative group was 86.4％(19/22).However,7.8％(5/64) children had abnormal renal function,in which the positive group was 9.5％(4/42) and the negative group was 4.5％(1/22).And 4.7％(3/64) children died,in which the positive group was 2.4％(1/42) and the negative group was 9.1％ (2/22).The one left (1.6％) showed dialysis dependence,which was positive for the auto-antibody.Multifactor Cox regression analysis showed that the age of less than 3 years old was the risk factor of poor prognosis (HR=4.651,95％CI 0.988-21.898,P=0.047).Conclusions The positive proportion of anti-factor H autoantibody in children with aHUS is high.The age of these children is older.Individualized therapy based on anti-factor H autoantibody and immunosuppressive therapy is of great significance for disease remission,preventing recurrence and improving the prognosis.Age less than 3 years old is the risk factor for poor prognosis.

Kidney Transplantation in Patients with Atypical Hemolytic Uremic Syndrome due to Complement Factor H Deficiency: Impact of Liver Transplantation

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare disease that is often associated with genetic defects. Mutations of complement factor H (CFH) are the most common genetic defects that cause aHUS and often result in end-stage renal disease. Since CFH is mainly produced in the liver, liver transplantation (LT) has been performed in patients with defective CFH. METHODS: The clinical courses of four kidney allograft recipients who lost their native kidney functions due to aHUS associated with a CFH mutation were reviewed. RESULTS: Subject A underwent kidney transplantation (KT) twice, aHUS recurred and the allograft kidney failed within a few years. Subject B received a KT and soon experienced a recurrence of aHUS coinciding with infection. Her allograft kidney function has worsened, and she remains on plasma infusion therapy. Subject C underwent LT followed by KT. She is doing well without plasma infusion therapy after combined LT-KT for 3 years. Subject D received KT following LT and is now recurrence-free from aHUS. CONCLUSION: In patients with aHUS associated with a CFH mutation, KT without LT was complicated with a recurrence of aHUS, which might lead to allograft loss. Conversely, LT was successful in preventing the recurrence of aHUS and thus might be another option for a recurrence-free life for aHUS patients associated with CFH mutation.

Association study of CFH gene polymorphisms with schizophrenia in Chinese Han population / 上海交通大学学报（医学版）

Objective·To investigate the correlation of single nucleotide polymorphism (SNP) of complement factor H (CFH) gene with schizophrenia in Chinese Han population.Methods·The genotype,allele,and haplotype frequencies of 5 SNP loci (rs800292,rs 1061170,rs 10801555,rs 10922096 and rs2019727) in CFH gene were compared between 418 patients with schizophrenia (case group) and 655 normal people (control group) by SNaPshot technique.Results·All SNP loci were well genotyped in the subjects.Correlation analysis showed that rs1061170 locus allele frequency distribution difference between case group and control group was statistically significant (corrected P=0.045),while genotype and allele frequencies of other SNP loci were not significantly different (all corrected P＞0.05).The frequency of haplotype C-A-T-A-A (rs800292-rs1061170-rs10801555-rs10922096-rs2019727) in case group was different from that in control group (corrected P=0.013).Conclusion·The allele polymorphisms of rsl061170 and the haplotype C-A-T-A-A of rs800292-rs 1061170-rs 10801555-rs 10922096-rs2019727 may be associated with schizophrenia in Chinese Han population.

Changes in complement factor H-related protein 2 in children with pulmonary arterial hypertension associated with congenital heart disease and its potential clinical significance / 中华实用儿科临床杂志

Objective To detect the changes and the clinical significance in plasma protein-complement factor H-related protein 2 (CFHR2) in pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) children.Methods Various types of 66 CHD patients with or without PAH and 16 healthy children(healthy control group) were studied,including 11 ventricular septal defects (VSD) with PAH (VSD-PAH),11 isolated VSD,11 atrial septal defects with PAH (ASD-PAH),11 isolated ASD,11 mixed type of heart defects [two or more defects of VSD,ASD and patent ductus arteriosus (PDA)] with PAH (Mix-PAH) and 11 cases without PAH (Mix).CFHR2 was validated by enzyme linked immunosorbent assay in the sample plasma.Results Compared with the healthy control group,the CFHR2 concentration in VSD-PAH patients [(189.10 ±24.01) μg/L vs.(42.99 ±4.53) μg/L,t =4.975,P ＜0.01] and VSD patients [(189.10 ±24.01) μg/L vs.(165.00 ±23.17) μg/L,t =2.661,P ＜ 0.05] were lower.The CFHR2 protein was also confirmed to be decreasing significantly in VSD-PAH patients compared with VSD patients (t =4.698,P ＜ 0.01).The plasma CFHR2 level in ASD-PAH patients [(189.10 ± 24.01)μg/L vs.(70.92 ± 8.27) μg/L,t =3.951,P ＜0.01] and ASD patients [(189.10 ±24.01) μg/L vs.(72.48 ± 8.99) μg/L,t =3.880,P ＜ 0.01] were significantly lower than those in the healthy control group,although there was no significant difference between ASD-PAH and ASD patients (t =0.128,P ＞ 0.05).The plasma CFHR2 level in Mix-PAH patients [(189.10 ± 24.01) μg/L vs.(83.23 ± 15.96) μL,t =3.314,P ＜ 0.05] was significantly lower than that in the healthy control group,while Mix patients [(189.10 ±24.01) μg/L vs.(170.40 ±33.15) μg/L,t =0.468,P ＞ 0.05] had no difference compared with the healthy control group,but had statistical significance with M ix PAH group (t =2.370,P ＜ 0.05).Conclusions The decrease of CFHR2 protein may demonstrate the deficiency of the immune system and coagulation mechanism in these patients and can be consi-dered as biomarker of CHD-PAH disease.

Advances in complement factor H gene in age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

?Age-related macular degeneration ( AMD) is one of the main leading causes of irreversible damage eyesight over the 50 years old people. Genetic factors play an important role in the occurrence and development of AMD. ln recent years, the studies found that complement factor H ( CFH) gene has obvious correlation with the incidence of AMD. ln this article, we reviewed the researches on the CFH in AMD.

Anesthetic management of living donor liver transplantation for complement factor H deficiency hemolytic uremic syndrome: a case report / 대한마취과학회지

We experienced a living donor liver transplantation for a 26-month-old girl with complement factor H deficiency. Complement factor H is a plasma protein that regulates the activity of the complement pathway. Complement overactivity induced by complement factor H deficiency is associated with atypical hemolytic uremic syndrome. Liver transplantation can be the proper treatment for this condition. During the liver transplantation of these patients, prevention of the complement overactivation is necessary. Minimizing complement activation, through the use of modalities such as plasma exchange before the surgery and transfusion of fresh frozen plasma throughout the entire perioperative period, may be the key for successful liver transplantation in these patients.

Pharmacogenetic Influence of LOC387715/HTRA1 on the Efficacy of Bevacizumab Treatment for Age-Related Macular Degeneration in a Korean Population

PURPOSE: The purpose of this study was to determine the pharmacogenetic effects of complement factor H (CFH) Y402H, LOC387715 and high-temperature requirement factor A1 (HTRA1) genotypes on the treatment of exudative age-related macular degeneration (AMD) by intravitreal bevacizumab injection in a Korean population. METHODS: Seventy-five patients diagnosed with exudative AMD were treated with intravitreal bevacizumab (2.5 mg) monotherapy. All patients received three initial intravitreal bevacizumab injections every four weeks and were then treated "as needed" based on clinical findings, optical coherence tomography and fluorescein angiography during the 12 month follow-up period after the third injection. RESULTS: The difference in visual acuity improvement among the three genotypes of LOC387715 were statistically significant at six months post-treatment (logarithm of the minimum angle of resolution; TT, 0.346; GT, 0.264; GG, 0.188; p = 0.037). Among the LOC387715 genotypes, the number of additional injections was lower in patients who had the risk T allele (GG, 2.143; GT, 2.000; TT, 1.575; p = 0.064). There was no significant difference between visual acuity and central macular thickness change in the CFH Y402H polymorphism group during the 12 month follow-up period. However, the TC group of CFH Y402H required more additional bevacizumab injections than the TT group (TT, 1.517; TC, 3.363; p = 0.020). CONCLUSIONS: This study demonstrated that different LOC387715/HTRA1 genotypes resulted in different bevacizumab treatment responses on exudative AMD. Patients with the risk allele had an improved treatment response and less need for additional injections. However, patients with the CFH Y402H risk allele needed more additional injections of bevacizumab in order to improve visual acuity. This study illustrates how pharmacogenetic factors may help determine treatment modality and dosing. This could ultimately provide basic data for 'personalized medicine' in AMD.

The correlation between single nucleotide polymorphism of complement factor H gene and exudative age-related macular degeneration / 中华眼底病杂志

ObjectiveTo investigate the correlation between single nucleotide polymorphism (SNP)of complement factor H (CFH) gene and exudative age-related macular degeneration (AMD) susceptibility.MethodsThis is a retrospective case control study. 136 exudative AMD patients (AMD group) and 140age and sex-matched normal subjects (control group) were enrolled in this study. The peripheral blood was collected,polymorphism genotypes and frequency of CFH Y402H(rs1061170),CFH-257C ＞ T (rs3753394) and CFH IVS15 (rs1329428)were measured by polymerase chain reaction (PCR) and allelespecific restriction endonuclease digestion. The SHEsis software was performed on haplotype construction to analyze the frequency.ResultsThere are TT, TC, CC genotypes and T, C allele in CFH Y402H (rs1061170); CC, CT, TT genotypes and C, T allele in CFH-257C＞T (rs3753394); AA, AG, GG genotypes and A, G allele in CFH IVS15 (rs1329428). The differences of genotypes and allele frequency between 2 groups were statistically significant (P＜0. 05). The TC genotype in CFH Y402H, TT genotype in CFH-257C＞T (rs3753394) and GG genotype in CFH IVS15 (rs1329428) were associated with exudative AMD susceptibility (OR=4. 11,2. 55,3.11;P＜0.05). The T, C and G allele were the risk alleles (OR=3.14,1.72,1.79;P＜0. 05). The differences of frequency between TCG, CTG and CTA haplotype were statistically significant(X2 =10.53,6.60, 32.82;P＜0.05). ConclusionThere is correlation between SNPs of CFH gene and exudative AMD susceptibility.

Progress on molecular genetics in atypical hemolytic uremic syndrome / 国际儿科学杂志

Atypical hemolytic uremic syndrome(aHUS) has recently been shown to be a rare disease of genetic predisposition, including genes of complement factor H(CFH), membrane cofactor protein(MCP, CD46)and complement factor Ⅰ(CFI), which are complement regulatory genes. Genes mutation is about 50%,involving the three genes mutation, including nonsense mutation, missen mutation, silent mutation, splice mutation and insertion mutation. Autosomal dominant inheritance and autosomal recessive inheritance have been reported, however, for autosomal dominant inheritance, the three genes mutations are incomplete penetrance.

The role of molecular genetic factors in age-related macular degeneration / A importância dos fatores genéticos na degeneração macular relacionada à idade

Age-related macular degeneration (AMD) is the most frequent cause of irreversible blindness in the elderly in developed countries. Although the etiology of AMD remains largely unknown, numerous studies have suggested that both genes and environmental risk factors significantly influence the risk of developing AMD. Recently, single nucleotide polymorphisms, DNA sequence variations found within the complement factor H (CFH) gene, have been found to be strongly associated with the development of AMD. Several other genes have had at least one positive association finding and deserve further exploration. The purpose of this review is to provide an extensive report of the current data of AMD genetics and the contribution of this knowledge helps to the better understanding of its pathophysiology.

A degeneração macular relacionada à idade (DMRI) é a causa mais frequente de cegueira irreversível em idosos em países desenvolvidos. Apesar da etiologia da DMRI ainda permanecer desconhecida, numerosos estudos tem sugerido que tanto fatores genéticos quanto ambientais influenciam significativamente no risco do desenvolvimento da doença. Recentemente, polimorfismos de base única, variações na sequência de DNA encontradas no gene fator H do complemento (CFH), tem sido fortemente associado com o desenvolvimento da DMRI. Muitos outros genes tiveram ao menos um resultado positivo para esta associação e merecem estudos posteriores. O objetivo dessa revisão é proporcionar descrição atual dos dados publicados.

A Case of Familial Atypical Hemolytic Uremic Syndrome Associated with Complement Factor H Mutation in Adults / 대한신장학회지

The hemolytic uremic syndrome is a clinical syndrome defined by the presence of thrombocytopenia, microangiopathic hemolytic anemia and acute renal failure. Atypical hemolytic uremic syndrome (aHUS) which is not usually associated with prodromal symptoms, especially diarrhea, has a higher mortality rate and a stronger tendency to progress to chronic renal failure. In approximately 30-50% of patients with aHUS, mutations have been detected in complement factor H, membrane cofactor protein or factor I. Mutations in the complement regulator factor H are the most frequent and have a very poor prognosis, with most patients developing ESRD. We have experienced a 33-year-old man with a family history of renal failure diagnosed as aHUS resulted from factor H mutation, for whom we carried out hemodialysis, plasmapheresis and other conservative management.

Regulative effect of complement factor H and adrenomedullin on HBZY-1 rat mesangial cells cultured under high glucose concentration / 中华内分泌代谢杂志

The renal protective effect of complement factor H(CFH)and adrenomedullin (AM) on rat mesengial ceils (HBZY-1) cultured under high glucose levels was investigated. Results indicated that AM and CFH inhibited the expressions of transforming growth factor-β1 and extracellular matrix in HBZY-1 cells, suggesting that CFH and AM in combination seem to show some renal protective effects on diabetic nephropathy.

Auxiliary Partial Orthotopic Liver Transplantations for One Pediatric Patient with Complement Factor H Deficiency and Two Adult Patients / 대한이식학회지

We have performed 3 cases of APOLT in one child and two adults. The child recipient had suffered from complement factor H deficiency since 3 months after birth and at the age of 30 months, APOLT was undertaken. Living donors of two adult recipients were affected by severe hepatic steatosis and the grafts were relatively small-for-size. After left hemihepatectomies, left lateral section and left hemilivers were transplanted orthotopically. The child recipient died of heart failure due to sepsis 7 months after transplantation, but factor H level remained nearly normal until his death. Although one adult suffered from hepatic venous stricture postoperatively, all adult recipients are alive with normal liver function for 11 and 8 months. In conclusion, although APOLT is technically demanding, APOLT may be a suitable surgical procedure in non-cirrhotic metabolic liver disease and a feasible solution for marked steatotic living donor grafts and small-for-size grafts.

Expression of Complement Regulator Genes in Abeta1-42 Stimulated Human Neuroblastoma Cell

BACKGROUND: Endogenous complement inhibitors in the brain may protect against the neuroinflammation in Alzheimer's disease. Human neuroblastoma cells were stimulated by Abeta1 - 4 2 to investigate whether the expression of various complement regulator genes is upregulated. METHODS: SK-N-SH cells were incubated overnight with a single dose of 20 microM of Abeta1-42 or 0.5 ng/ml - 5 ng/ml of TNFalpha or both. Actinomycin D (2.5 microM) or cycloheximide (2.5 microM) was also added to the cell suspension. Messenger RNA expression of decay accelerating factor (DAF), membrane cofactor protein (MCP), CD59, complement-receptor 1(CR1), C1 inhibitor (C1-INH), C4-binding protein, factor H, factor I, clusterin and S-protein was measured by RT-PCR. RESULTS: Abeta1-42 and TNFalpha upregulated the expression of C1- INH significantly but increased expression of mRNA for factor H was not statistically significant. The expression of mRNAs for DAF and MCP was at low a level after stimulation. Factor I, CD59 and clusterin were not changed in their mRNA level. The mRNAs for S-protein, C4-binding protein and CR1 were not detected. Actinomycin D suppressed mRNA levels of C1-INH and CD59 significantly. Cycloheximide also inhibited the expression of both C1-INH and CD59. CONCLUSIONS: Early upregulated expression of C1-INH in Abeta1-42 stimulated neuroblastoma cell may contribute to a host defense mechanism against complement-mediated neuronal cell damage.

Expression of Complement Regulator Genes in Abeta1-42 Stimulated Human Neuroblastoma Cell

BACKGROUND: Endogenous complement inhibitors in the brain may protect against the neuroinflammation in Alzheimer's disease. Human neuroblastoma cells were stimulated by Abeta1 - 4 2 to investigate whether the expression of various complement regulator genes is upregulated. METHODS: SK-N-SH cells were incubated overnight with a single dose of 20 microM of Abeta1-42 or 0.5 ng/ml - 5 ng/ml of TNFalpha or both. Actinomycin D (2.5 microM) or cycloheximide (2.5 microM) was also added to the cell suspension. Messenger RNA expression of decay accelerating factor (DAF), membrane cofactor protein (MCP), CD59, complement-receptor 1(CR1), C1 inhibitor (C1-INH), C4-binding protein, factor H, factor I, clusterin and S-protein was measured by RT-PCR. RESULTS: Abeta1-42 and TNFalpha upregulated the expression of C1- INH significantly but increased expression of mRNA for factor H was not statistically significant. The expression of mRNAs for DAF and MCP was at low a level after stimulation. Factor I, CD59 and clusterin were not changed in their mRNA level. The mRNAs for S-protein, C4-binding protein and CR1 were not detected. Actinomycin D suppressed mRNA levels of C1-INH and CD59 significantly. Cycloheximide also inhibited the expression of both C1-INH and CD59. CONCLUSIONS: Early upregulated expression of C1-INH in Abeta1-42 stimulated neuroblastoma cell may contribute to a host defense mechanism against complement-mediated neuronal cell damage.