PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Hereditary Complement Deficiency Diseases”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed1990

Prevalence of hereditary properdin, C7 and C8 deficiencies in patients with meningococcal infections.

High incidence of hereditary complement (C) deficiencies was found among 101 patients who had a meningococcal disease. This study revealed 11 non-related patients with complete C deficiency: five deficient in C7, three in C8, two in properdin and one in C2. Additional C-deficient individuals, most of them with no history of severe bacterial infections, were detected in family studies. The C8-deficient patients were found to have a selective deficiency of the C8-beta subunit and a reduced expression of the alpha/gamma subunit. Only a few families with properdin deficiency have been described so far. However, it is likely that frequent analysis of the activity of the alternative C pathway in survivors of severe bacterial infections will disclose numerous properdin-deficient patients. All our C7-, C8- and properdin-deficient patients are Sephardic Jews whose families originated from Morocco, Yemen (C7 and C8 deficient) or Tunisia (properdin deficient). This and other findings indicate that the type of complement abnormality found in association with meningococcal infections varies with the ethnic origin of the patient.

Adolescent↗
PubMed1990

Dapsone is an effective therapy for the skin lesions of subacute cutaneous lupus erythematosus and urticarial vasculitis in a patient with C2 deficiency.

The deficiency of second component of complement (C2d) is the most common hereditary complement deficiency. Patients with C2 deficiency are frequently associated with an auto-immune disease process, in particular, systemic lupus erythematosus (LE)-like syndrome and/or vasculitic syndrome or bacterial infections. C2d has been associated with the LE subset of subacute cutaneous LE (SCLE), the presence of anti-Ro (SSA) antibodies, and the human leukocyte antigen (HLA) types A10, B18, DR2. We describe the clinical, serologic and immunogenetic data in a patient with manifestations of Sjögren's syndrome who developed urticarial vasculitis and photosensitive annular SCLE which were effectively treated with oral dapsone. Our case illustrates the dynamic nature of LE.

Administration, Oral↗
PubMed1990

[Clinical contribution to the problem of correlations between hereditary angioneurotic edema and pregnancy].

Hereditary angioneurotic edema (HAE) is an autosomal dominant disease caused by a deficiency of a complement regulatory protein, the C1INH.HAE is clinically characterized by recurrent, self-limited attacks of edema involving the extremities, face, upper respiratory tract or gastrointestinal tract. Pregnancy in a woman affected by HAE poses therapeutical problems. In fact, prophylactic treatment with danazole or tranexamic acid is control indicated in a pregnant woman. However HAE shows a favourable course in most cases and the delivery, despite the local trauma, is not usually associated with complications. But the occasional occurrence of local edema and the literature report of a death in postpartum, suggest the administration of purified C1INH prophylactically before the delivery. HAE, per sé, neither alters the evolution of pregnancy nor does foetus harm. The A. report on a 22-years old primigravida affected by HAE. She had no attack during the whole gestation, the delivery and the postpartum. She was given 1000 units of purified C1INH concentrate both four hours before the delivery and 24 hours after it.

Adult↗
PubMed1998

Complement regulation.

Because of its strong potential for generating inflammation and causing tissue destruction the complement system has to be kept strictly under control. Cells of the host need special protection against the cytolytic complement system. This paper will describe how inappropriate activation of complement in the fluid phase is prevented and how viable human blood cells defend themselves against being destroyed and cleared away by the complement system. Since disturbances in complement regulation occasionally result in disease a brief reference will be made to two of the syndromes caused by complement regulator deficiency, hereditary angioedema (HAE) and paroxysmal nocturnal hemoglobinuria (PNH).

Angioedema↗
PubMed1995

Porcine membranoproliferative glomerulonephritis type II: an autosomal recessive deficiency of factor H.

Hypocomplementaemic hereditary membranoproliferative glomerulonephritis (MPGN) type II is a common cause of the early loss of piglets in the Norwegian Yorkshire breed. The disease is associated with extensive complement activation due to a deficiency of factor H, a plasma protein which regulates complement. To investigate its mode of inheritance, 33 litters were bred from healthy animals associated with the disease, and a total of 385 recorded offspring were produced. The examination of renal tissue from the hypocomplementaemic piglets consistently revealed diagnostic signs of MPGN type II, including thickening of the glomerular capillary wall and proliferation of mesangial cells, dense intramembranous deposits, and massive glomerular deposits of complement component C3 and the terminal complement complex. No such glomerular lesions were detected in 20 normocomplementaemic littermates. The 88 affected piglets were present in 27 litters containing a total of 317 piglets, and there were approximately equal numbers of each sex. Retrospective immunoblot analysis and enzyme immunoassay of plasma samples from the MPGN-affected piglets and their healthy littermates revealed that the affected piglets were deficient in factor H, whereas the healthy piglets were not. It is concluded that porcine factor H deficiency is inherited as a simple autosomal recessive trait with complete penetrance, and consistently results in hypocomplementaemia and lethal membranoproliferative glomerulonephritis type II.

Animals↗
PubMed1990

[Lupus and protein deficiencies of the classical complement pathway].

Deficiencies in proteins of the classic complement pathway are particularly frequent in patients with autoimmune diseases, notably systemic lupus erythematosus (SLE). The C4 component is a polymorphous glucoprotein coded by two closely linked genes, C4A and C4B, located within the HLA complex. C4, and in particular the C4A isotype plays a major role in maintaining immune complexes in solution. Fifty percent of patients with SLE are homozygous or heterozygous to the silent allele C4 AQO. Hereditary CE deficiency is often complicated by lupus-related diseases which may be associated with repeated infections. The biological particularity of SLE associated with complement protein deficiencies is the frequency of anti-SSA (Ro) antibodies.

Complement C2↗
PubMed1999

[Hereditary or acquired angioedema caused by functional deficiency of C1 inhibitor--a still unfamiliar disease picture].

Hereditary angioneurotic oedema or hereditary angiooedema (HAE) and acquired angiooedema (AAE) are disorders of the C1-inhibitor (C1-INH) protein, caused by the lack, dysfunction or exhaustion of the C1-INH molecule. Inadequate function of C1-INH results in inappropriate control of various enzymes of the fibrinolytic, complement and kinin systems as well as of factor XII, being the initial enzyme of the kinin and contact coagulation systems. As C1-INH functional deficiency is rare and the clinical manifestation little known, even nowadays the most feared complication of the deficiency may evolve: death from acute airway obstruction. Patients deficient in C1-INH function whose clinical manifestations are misinterpreted as allergic angiooedema are most at risk for fatal laryngeal oedema. The therapy of allergic and C1-INH-related angiooedema is fundamentally different. The background for the hereditary form of inadequate C1-INH function is a gene defect. The predominant primary underlying disease of the acquired form of the deficiency (AAE) is a lymphoproliferative process.

Angioedema↗
PubMed1978

Hereditary C2 deficiency associated with immune complex disease.

A patient presenting with a syndrome probably due to immune complex deposition was investigated and found to possess an inherited C2 complement deficiency. Family studies indicated that the deficiency was transmitted as an autosomal recessive trait. HLA typing for the HLA-A and HLA-B specificities and HLA-D specificities indicated a close linkage between the HLA and C2 genes, as has been described elsewhere. The HLA-A and B locus specificities HLA-AW25 and HLA-B18 were coded for by each of the two chromosomes carrying the C2(0) gene. However, the two chromosomes differed at the HLA-D locus, as one coded for HLA-DW2 whilst the other did not. This case, therefore, provides a unique haplotype and may be of importance in mapping the C2(0) locus, as it suggests that the gene order on chromosome 6 is HLA-D, C2(0), HLA-B, HLA-A. Extensive complement component assays indicated that utilization of complement in the patient was occurring via the alternate complement pathway. It is suggested that, as a result of the C2 deficiency, infections with viruses and other agents could lead to an immune complex disease due to an impaired capacity to effectively eliminate circulating complexes.

Adult↗
PubMed2000

Complement deficiencies.

The complement proteins play an important role in innate immunity, promoting inflammation and microbial killing. They play a role in the adaptive immune response, as well. Inherited total deficiencies of complement proteins are extremely rare. Table 1 lists more than 40 proteins that comprise the elements of the complement system. Deficiency of the proteins that promote lysis and opsonization is so rare that two papers are able to list all the observed cases to 1991. The exception is mannan-binding lectin, in which deficiency may be commoner. Diseases of regulatory proteins, such as occurs in hereditary angioedema or paroxysmal nocturnal hemoglobinuria, are commoner but still are quite rare. As we learn more about complement proteins and their mechanism of action, we will understand more clearly how these proteins function. Polymorphisms of the proteins exists. Learning how these polymorphisms contribute to the development of disease will be the focus of complement studies in the next decade.

Child↗
PubMed2005

Angioedema.

UNLABELLED: Although first described more than 130 years ago, the pathophysiology, origin, and management of the several types of angioedema are poorly understood by most dermatologists. Although clinically similar, angioedema can be caused by either mast cell degranulation or activation of kinin formation. In the former category, allergic and nonsteroidal anti-inflammatory drug-induced angioedema are frequently accompanied by urticaria. Idiopathic chronic angioedema is also usually accompanied by urticaria, but can occur without hives. In either case, an autoimmune process leading to dermal mast cell degranulation occurs in some patients. In these patients, histamine-releasing IgG anti-FcepsilonR1 autoantibodies are believed to be the cause of the disease, removal or suppression by immunomodulation being followed by remission. Angiotensin-converting enzyme inhibitor-induced angioedema is unaccompanied by hives, and is caused by the inhibition of enzymatic degradation of tissue bradykinin. Hereditary angioedema, caused by unchecked tissue bradykinin formation, is recognized biochemically by a low plasma C'4 and low quantitative or functional C'1 inhibitor. Progress has now been made in understanding the molecular genetic basis of the two isoforms of this dominantly inherited disease. Recently, a third type of hereditary angioedema has been defined by several groups. Occurring exclusively in women, it is not associated with detectable abnormalities of the complement system. Angioedema caused by a C'1 esterase inhibitor deficiency can also be acquired in several clinical settings, including lymphoma and autoimmune connective tissue disease. It can also occur as a consequence of specific anti-C'1 esterase autoantibodies in some patients. We have reviewed the clinical features, diagnosis, and management of these different subtypes of angioedema. LEARNING OBJECTIVE: After completing this learning activity, participants should be aware of the classification, causes, and differential diagnosis of angioedema, the molecular basis of hereditary and non-hereditary forms of angioedema, and be able to formulate a pathophysiology-based treatment strategy for each of the subtypes of angioedema.

Acute Disease↗
PubMed1975

Complement component analysis in angiodema. Diagnostic value.

Complement component analysis is valuable for differentiating the various types of angioedema. Patients with hereditary angioedema have decreased levels of C1 esterase inhibitor and C4 in the presence of normal amounts of C3 and C1q. Acquired C1 esterase inhibitor deficiency secondary to malignant disease is also manifested by depressed C1 esterase inhibitor and C4, but decreased C1q levels distinguish it from hereditary angioedema. Normal values for these complement components are found in persons with allergic angioedema.

Angioedema↗
PubMed1991

C1-INH defect as an example of deficiency disease.

Primary defect of C1-inhibitor (C1-INH), the regulatory protein of the initial classical pathway of complement, is the cause of hereditary angioedema. Clinical symptoms involve potentially fatal obstruction of the upper respiratory tract, abdominal pains, and subcutaneous edemas. Since the description of functional tests for C1-INH two types of hereditary defect have been known: type I and type II. Sixteen patients with the type I of hereditary angioedema were diagnosed and treated in our hospital. The onset of the disease occurred between 1.5-12 y. of age. Clinical symptoms were observed in skin, gastrointestinal and respiratory tracts. Mean concentration of C1-INH in sera of 16 patients was 3.25 mg/dl, below 8.75 mg/dl that is the critical for well-functioning C1-INH. Inhibitory activity of C1-INH for C1 esterase in plasma was zero in most of the patients, while it was 0.94 +/- 0.20 U/ml in plasma samples of 91 healthy blood donors. Three modalities of treatment are available: substitution with C1-INH concentrate in acute attacks and antifibrinolytic and/or anabolic drugs for prophylaxis. We have obtained good therapeutic results with epsilon-aminocaproic acid (antifibrinolytic), 2g daily during 3 months, with 6 months intervals.

Adolescent↗
PubMed1991

Complement deficiency and disease.

Complement deficiency is associated with an increased prevalence of pyogenic infections and immune complex disease. The spectrum of disease in deficient individuals depends on the stage in the complement system at which the block in activation occurs. Here, Paul Morgan and Mark Walport review current knowledge of hereditary complement deficiencies in humans, emphasizing the importance of these 'experiments of nature' in defining the roles of complement in vivo.

Bacterial Infections↗
PubMed1995

Acquired deficiency in C1-inhibitor associated with signet ring cell gastric adenocarcinoma: a probable connection of antitumor-associated antibodies, hemolytic anemia, and complement turnover.

BACKGROUND: Acquired deficiency in C1-inhibitor (C1-INH) associated with malignancy is often asymptomatic because clinical manifestations are not dependent on a critical complement threshold (in contrast to hereditary C1-INH deficiency). Increased complement consumption involving different kinds of antibodies is the postulated mechanism for this disease, but other factors must play an important role. CASE REPORT: A 76-year-old woman with unremarkable medical history experienced three episodes of angioedema over 6 months. Investigations revealed a complement profile characteristic of acquired deficiency in C1-INH, a hemolytic anemia, and a signet ring cell adenocarcinoma (linitis plastica). A gastrectomy and a splenectomy were performed. The postoperative course was characterized by a complete disappearance of the symptoms of angioedema and hemolytic anemia. A local recurrence of the tumor 5 months later could not be resected. The patient died 17 months after the initial surgery was performed. RESULTS: Quantitative and functional analyses of the complement factors showed persistent excessive complement consumption. Markers of hemolytic anemia disappeared after tumor removal but recurred in the second part of the disease evolution. Immunohistochemical findings in tumor tissue showed loss of normal blood group antigens but expression of Lea antigen, as well as C1q deposition. CONCLUSION: To explain the whole clinical and laboratory picture, we hypothesize a connection between tumor immunohistochemical profile, complement consumption, and hemolytic anemia. Tumor cell surface antigens might lead to a permanent but asymptomatic complement consumption that is worsened and becomes clinically manifest by superimposed hemolytic anemia caused by cross-reactive antibodies to newly expressed blood group antigens on tumor cells. This hypothesis should be confirmed by other observations.

Aged↗
PubMed1987

Hereditary complement (C6) deficiency associated with systemic lupus erythematosus, Sjögren's syndrome and hyperthyroidism.

Results of clinical, serologic and histologic studies documenting an association between hereditary C6 deficiency and a connective tissue disease are provided. The propositus had systemic lupus erythematosus with prominent discoid features, Sjögren's syndrome and hyperthyroidism. Serum C6 was undetectable by radial immunodiffusion and hemolytic assays. Serologic and typing studies performed on 9 family members suggested an autosomal codominant transmission. No correlation with a specific HLA phenotype was established.

Complement C6↗
PubMed1982

[Hereditary complement deficiencies].

Complement deficiencies of all nine C-components have been observed. Hereditary defects of early components of the classical pathway - C1, C4, C2 - are often associated with diseases of the immuncomplex-type especially with systemic lupus erythematosus, dermatomysitis, vasculitis and nephritis. Deficiencies of C3 and C3b inactivator are linked to severe and recurrent bacterial infections. Patients with hereditary defects of the so-called late components, C5-C9, show increased susceptibility to recurrent disseminated infections by neisseria gonorrhoeae and meningitidis. The most frequent of the defects of the complement system is the hereditary deficiency of C1-inactivator which is associated with hereditary angioneurotic edema. In this paper the C-defects and their genetics are described and possible pathomechanisms are discussed.

Complement Activating Enzymes↗
PubMed1987

Altered C1 inhibitor genes in type I hereditary angioedema.

Hereditary angioedema is an inherited disease transmitted as an autosomal dominant trait and characterized by deficient activity of C1 inhibitor, a glycoprotein that limits intravascular activation of complement. The unavailability of markers for the C1 inhibitor locus has so far precluded access to the genetic bases of the disorder. Using a recombinant-DNA probe for the C1 inhibitor gene, we identified a cluster of four distinctive DNA restriction sites in a multigeneration family. The strict cosegregation of these markers with a low C1 inhibitor level supports the conclusion that a defective structural gene is responsible for the disease. The occurrence of distinct DNA markers in patients from unrelated kinships indicates that, like forms of the condition displaying dysfunctional C1 inhibitor variants, those characterized by protein deficiency are also genetically heterogeneous. Although multiple restriction-site changes in the C1 inhibitor gene are carried by certain patients, DNA markers for this locus are strikingly infrequent among normal persons. These findings indicate that the gene alterations responsible for hereditary angioedema arise more often from DNA rearrangements than from nucleotide substitutions. Such variations in the structure of the C1 inhibitor gene may provide the basis for early and direct identification of persons at risk.

Angioedema↗