No abstract available.
Complement Factor H*

Complement Factor H ; genetics ; Hemolytic-Uremic Syndrome ; genetics ; Humans

Autoantibodies ; Child ; Complement Factor H ; immunology ; Female ; Hemolytic-Uremic Syndrome ; immunology ; Humans

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.
Child, Preschool ; Complement Activation ; Complement Factor H* ; Complement System Proteins ; Female ; Hemolytic-Uremic Syndrome* ; Humans ; Liver Transplantation* ; Living Donors* ; Perioperative Period ; Plasma ; Plasma Exchange

Complement proteins in blood recognize charged particles. The anionic phospholipid (aPL) cardiolipin binds both complement proteins C1q and factor H. C1q is an activator of the complement classical pathway, while factor H is an inhibitor of the alternative pathway. To examine opposing effects of C1q and factor H on complement activation by aPL, we surveyed C1q and factor H binding, and complement activation by aPL, either coated on microtitre plates or in liposomes. Both C1q and factor H bound to all aPL tested, and competed directly with each other for binding. All the aPL activated the complement classical pathway, but negligibly the alternative pathway, consistent with accepted roles of C1q and factor H. However, in this system, factor H, by competing directly with C1q for binding to aPL, acts as a direct regulator of the complement classical pathway. This regulatory mechanism is distinct from its action on the alternative pathway. Regulation of classical pathway activation by factor H was confirmed by measuring C4 activation by aPL in human sera in which the C1q:factor H molar ratio was adjusted over a wide range. Thus factor H, which is regarded as a down-regulator only of the alternative pathway, has a distinct role in downregulating activation of the classical complement pathway by aPL. A factor H homologue, β2-glycoprotein-1, also strongly inhibits C1q binding to cardiolipin. Recombinant globular domains of C1q A, B and C chains bound aPL similarly to native C1q, confirming that C1q binds aPL via its globular heads.
Animals ; Complement Activation ; Complement C1q ; chemistry ; metabolism ; Complement Factor H ; metabolism ; Humans ; Immunoglobulin G ; metabolism ; Mice ; Phospholipids ; chemistry ; metabolism ; Protein Binding

OBJECTIVEA R1210C mutation of complement factor H (CFH) gene has been associated with age-related macular degeneration (AMD) in Caucasian population. This study was to verify above association in Han Chinese population.

METHODSThe mutation was detected by direct sequencing in 258 patients with wet AMD and 426 matched controls.

RESULTSThe R1210C mutation has not been identified in either sample.

CONCLUSIONThe R1210C mutation in CFH gene is not associated with AMD in Han Chinese population.

Aged ; Aged, 80 and over ; Complement Factor H ; genetics ; Female ; Humans ; Macular Degeneration ; genetics ; Male ; Middle Aged ; Mutation

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.
Adult* ; Child ; Complement Factor H* ; Complement System Proteins* ; Constriction, Pathologic ; Heart Failure ; Humans ; Liver Diseases ; Liver Transplantation* ; Liver* ; Living Donors ; Parturition ; Sepsis ; Transplants

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.
Allografts ; Atypical Hemolytic Uremic Syndrome ; Complement Factor H ; Complement System Proteins ; Humans ; Kidney Failure, Chronic ; Kidney Transplantation ; Kidney ; Liver Transplantation ; Liver ; Plasma ; Rare Diseases ; Recurrence

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.
Adolescent ; Anemia, Hemolytic ; Atypical Hemolytic Uremic Syndrome ; Autoantibodies ; Child ; Complement C3 ; Complement C4 ; Complement Factor H ; Complement Pathway, Alternative ; Female ; Humans ; Immunosuppression ; Kidney ; Laos ; Plasma ; Shiga-Toxigenic Escherichia coli ; Thrombocytopenia ; Thrombotic Microangiopathies

The complement system is known to be involved in the pathogenesis of the skin lesions in pernphigus vulgaris, bullous pemphigoid, dermatitis herpetiformis, epidermolysis bullosa acquisita, and systemic lupus erythematosus. Authors examined the skin specimens of each disease cases, who did not show any evidence of complement deficiency, to determine the deposition of complement components(C4, C3, Chb-9) and their inhibitors(C4bp, Factor H, S-protein) by modified direct immunofluorescence. We also looked at the staining pattern and localization, for further insights of their pathobiologic contributions in each disease. The findings of deposits of complement components up to C9, as well as inhibitor proteins at the primary histopathologic sites, in the majority of those cases, may indicate that the complement system, to certain extent, involves the inflamrnatory reactions in these diseases. The co-localization of C5b-9 and S-protein could be regarded as the consequence of in situ formation of SC5b-9 complexs or as the result of non-lytic adsorbed complexes of fluid phase SC5b-9. The pathologic role of the complement seems to depend mostly on the complement-fixing biologic property and the amount of the tissue bound immune complexes, which are often heterogeneous to different diseases and among different patients.
Antigen-Antibody Complex ; Complement Factor H ; Complement Membrane Attack Complex ; Complement System Proteins* ; Dermatitis Herpetiformis ; Epidermolysis Bullosa Acquisita ; Fluorescent Antibody Technique, Direct ; Humans ; Lupus Erythematosus, Systemic ; Pemphigoid, Bullous ; Skin ; Skin Diseases*