Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Complement C1 Inhibitor Protein”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 1,279 records · Page 71Linked to original sources
PubMed1989

[A case of hereditary angioneurotic edema associated with systemic lupus erythematosus].

A 33-year-old woman noticed recurrent and sudden attacks of subcutaneous swelling of the extremities and face since the age of 4 years. Sometimes the attacks involved colicky abdominal pain. Her mother and younger sister had episodes of recurrent swelling of the extremities as well. Complement studies revealed low CH50, C1q, C4, and C1 inhibitor levels, with normal C3 and C5 levels. Similar reductions of CH50 C4 and C1 inhibitor levels were observed in her mother, older, and younger sisters. Therefore, she was diagnosed as hereditary angioneurotic edema. In addition, she was diagnosed as having a butterfly rash at the age of 20 years and had a history of solar sensitivity. Histologically the facial lesion showed liquefaction degeneration of the basal cell layer. Direct immunofluorescent staining of the affected skin lesion showed basement membrane-zone staining of IgG and IgM. Laboratory studies revealed lymphopenia and positive ANF. On the basis of the above findings, hereditary angioneurotic edema associated with systemic lupus erythematosus was diagnosed.

Adult↗
PubMed1975

Effects of human C 1 inhibitor on complement-mediated human leukocyte chemotaxis.

Human C1 inhibitor (C1 INH) enhances the chemotactic responsiveness of human leukocytes to lipopolysaccharide (LPS), AgAb complex, and zymosan-activated plasma or serum when added to the compartment of the chemotaxis chamber containing the cells. It seems to affect cells directly and causes an increased number of leukocytes to respond to the chemotactic factors at early time intervals. Spontaneous motility does not appear to be affected. Results of studies employing anti-C3 and anti-C5 sera seem to indicate that the chemotactic factor derived from C5 is involved in the C1 INH induced enhancement of chemotaxis. In fact, preliminary experiments utilizing trypsinactivated C3 as a chemotactic source indicate that C1 INH causes inhibition of chemotactic response to C3a. C1 INH is the first naturally occurring plasma component reported to cause enhanced chemotactic responsiveness.

Adsorption↗
PubMed1995

The effect of WSEWS pentapeptide and WSEWS-specific monoclonal antibodies on constitutive and IL-6 induced acute-phase protein production by a human hepatoma cell line, HEPG-2.

Interleukin-6 receptor (IL-6R) is a member of the cytokine receptor superfamily characterised by the obligatory presence of WSXWS (Trp-Ser-X-Trp-Ser) sequence motif near the transmembrane domain. To more clearly understand the role of this motif, we treated the HepG2 hepatoma cell line with synthetic WSEWS peptide (E is glutamic acid) and checked the spontaneous and IL-6-induced production of acute-phase protein fibrinogen and C1-inhibitor (C1-INH). The peptide revealed a definitely stimulatory effect both on the constitutive synthesis of C1-INH and on the IL-6-induced fibrinogen synthesis of HepG2 cells. Monoclonal antibody specific for WSEWS pentapeptide was stimulatory for the spontaneous secretion of both fibrinogen and C1-INH. However, the IL-6-induced elevations of these acute-phase proteins were oppositely regulated, since the anti-WSEWS monoclonal antibody was inhibitory on the production of fibrinogen induced by IL-6 but strongly augmented the IL-6 induced production of C1-INH. Our study indicates that the WSEWS motif is critical in the effect of IL-6 on the acute-phase protein production influencing either the ligand binding by the WSEWS-containing receptor molecule or the signal transduction.

Acute-Phase Proteins↗
PubMed2002

Polyclonal autoantibodies against C1 inhibitor in a case of acquired angioedema.

BACKGROUND: Angioedema attributable to acquired C1 inhibitor (C1-INH) deficiency is a rare disease related to lymphoproliferative disorders or autoantibodies to Cl inhibitor. We describe a patient with angioedema and autoantibodies to C1 inhibitor. OBJECTIVE: To study the characteristics of autoantibodies to C1-INH in a patient with acquired angioedema. METHODS: Autoantibodies to Cl-INH were measured by enzyme-linked immunoadsorbent assay. Immunoglobulin (Ig)G autoantibody was purified by affinity chromatography on a protein G agarose column. We developed an enzyme-linked immunoadsorbent assay to determine whether the autoantibodies were directed against the C1-INH active center. RESULTS: IgM and mainly C1-INH IgG autoantibodies were detected; both had kappa and lambda chains. No monoclonal component was detected. The autoantibodies were directed against the Cl-INH active center. After various treatment strategies were attempted, an effective clinical response was attained with antifibrinolytic therapy. CONCLUSION: A case of acquired angioedema because of C1-INH deficiency was found to be attributable to the presence of polyclonal autoantibodies to C1-INH.

Aged↗
PubMed1980

[Immunological study of alopecia areata].

Sixteen patients with varying degrees of alopecia areata, without an associated disease were examined before and during a local DNCB therapy for evidence of immunological abnormalities in both cellular and humoral immune parameters. The mean values of IgG, IgA, IgM, IgE, complement factors C3 and C4 and of alpha 1-antitrypsin were found within the norm, of the C1-Inhibitor slight diminished. Antinuclear antibodies in low titer were observed in three, antithyroglobulin antibodies in two young patients. Immuncomplexes were always negative. The mean value for T cells (67 +/- 7%) was normal as well as the lymphocyte transformation to phytohemagglutin, pokweed-mitogen and candidin, the PPD stimulation was slight reduced. No changes in the immunprofile were observed during the DNCB therapy, with exception of a slight, but significant increase of the T cell number from 63 +/- 8% to 77 +/- 5%. Our findings exclude a common systemic immune defect in alopecia areata.

Adolescent↗
PubMed2001

C1-Inhibitor for treatment of acute vascular xenograft rejection in cynomolgus recipients of h-DAF transgenic porcine kidneys.

At present, the major barrier to successful discordant xenotransplantation of unmodified or complement regulator transgenic porcine xenografts is acute vascular xenograft rejection (AVR). AVR is associated with the intragraft deposition of induced recipient xenoreactive antibodies and subsequent complement activation. In a life-supporting pig to primate kidney xenotransplantation setting using h-DAF transgenic donor organs and postoperative immunosuppression, episodes of AVR were either treated with boluses of cyclophosphamide and steroids or with the same regimen supplemented by a three-day course of C1-Inhibitor, a multifunctional complement regulator. In 8 out of 10 animals stable initial graft function was achieved; in all animals one or more episodes of AVR were observed. When, in 4 animals, C1-Inhibitor was added to the standard anti-rejection treatment regimen, AVR was successfully reversed in 6 out of 7 episodes, while in another group of 4 animals receiving the standard anti-rejection treatment 0 out of 4 episodes of AVR responded to treatment. Response to anti-rejection treatment was associated with a significant increase in recipient survival time. We conclude that AVR of h-DAF transgenic porcine kidneys can be successfully treated by additional short-term fluid phase complement inhibition.

Animals↗
PubMed2005

The extracellular matrix and inflammation: fibromodulin activates the classical pathway of complement by directly binding C1q.

Components that propagate inflammation in joint disease may be derived from cartilage since the inflammation resolves after joint replacement. We found that the cartilage component fibromodulin has the ability to activate an inflammatory cascade, i.e. complement. Fibromodulin and immunoglobulins cause comparable deposition of C1q, C4b, and C3b from human serum. Using C1q and factor B-deficient sera in combination with varying contents of metal ions, we established that fibromodulin activates both the classical and the alternative pathways of complement. Further studies revealed that fibromodulin binds directly to the globular heads of C1q, leading to activation of C1. However, deposition of the membrane attack complex and C5a release were lower in the presence of fibromodulin as compared with IgG. This can be explained by the fact that fibromodulin also binds complement inhibitor factor H. Factor H and C1q bind to non-overlapping sites on fibromodulin, but none of the interactions is mediated by the negatively charged keratan sulfate substituents of fibromodulin. C1q but not factor H binds to an N-terminal fragment of fibromodulin previously implicated to be affected in cartilage stimulated with the inflammatory cytokine interleukin 1. Taken together our observations indicate fibromodulin as one factor involved in the sustained inflammation of the joint.

Complement Activation↗
PubMed1976

Detection of circulating antigen-antibody complexes by their inhibitory effect on the agglutination of IgG-coated particles by rheumatioid factor of Clq.

The agglutination of Ig-coated particles by human RF or Clq can be inhibited by Ig aggregates or AgAb complexes. The effect of Ig class was studied by means of agarose-linked human monoclonal Igs. RF was inhibited by all subclasses of IgG and IgA but not by IgM, whereas Clq reacted with IgM, IgG3 and IgG1. Heat-aggregated IgG3 was fractionated by gel-filtration on Ultrogel. Inhibition was restricted to certain fractions of aggregates, viz (IgG3) approximately 7 and (IgG3) approximately 21 for RF, and (IgG3) approximately 10, (IgG3) approximately 14 and (IgG3) approximately 27 for Clq. In a precipitin curve experiment, it was found that RF was inhibited by soluble complexes over an extended range of AgAb ratios, the inactivation of Clq being limited to complexes with 2-5 times antigen excess. Inhibiting factors were found in patients with various diseases and, at low titres, in 22% of healthy people. In 27% of patients' sera, the inhibitors were demonstrable by Clq only after removal of endogenous RF by adsorption on insolubilized IgG. In several patients endogenous agglutinating activity and direct inhibitory activity tended to alternate during the course of the disease. Sera from various patients were also filtrated on Ultrogel and the elution was monitored by immunoassay of IgA, IgM and IgG, as well as by the two inhibition tests. The inhibiting factors were distributed over several peaks which only partially coincided with the elution profiles of IgG and IgM.

Agglutination Tests↗
PubMed1989

The structural basis for neutrophil inactivation of C1 inhibitor.

Limited proteolysis of C1 inhibitor (C1-INH) by neutrophil elastase, Pseudomonas elastase and snake venoms resulted in initial cleavage within the molecule's N-terminus followed by further cleavage within the molecule's C-terminally placed reactive centre. N-Terminal proteolysis occurred at peptide bonds 14-15, 36-37 and 40-41. This had no effect on either the inhibitory activity or the heat-stability of C1-INH. Proteolysis within the reactive centre occurred at peptide bonds 439-440, 440-441, 441-442 and 442-443. Cleavage at any one of these sites inactivated C1-INH and conferred enhanced heat-stability upon a previously heat-labile molecule. Released neutrophil proteinases also cleaved and inactivated C1-INH, suggesting that they may physiologically regulate C1-INH during inflammatory episodes.

Animals↗
PubMed1997

Combined treatment with C1 esterase inhibitor and antithrombin III improves survival in severe acute experimental pancreatitis.

BACKGROUND: Patients with severe acute pancreatitis die of complications closely related to the systemic activation of protease cascades. AIM: To examine the effects of human C1 esterase inhibitor (C1 INH) and antithrombin III (AT III) on two experimental models of acute pancreatitis. METHODS: Oedematous pancreatitis was induced by continuous intravenous infusion of caerulein and haemorrhagic pancreatitis by retrograde injection of sodium taurocholate into the biliopancreatic duct. C1 INH and AT III were given intravenously, either before or after the induction of pancreatitis. Treatment with C1 INH and AT III had no beneficial effect on oedematous pancreatitis. On the other hand, combined C1 INH and AT III therapy improved the survival in haemorrhagic pancreatitis compared with treatment with human serum albumin. This reduction in mortality was found regardless of whether the treatment was given prophylactically or therapeutically. CONCLUSIONS: Treatment with C1 INH and AT III represents a promising therapeutic concept for patients with severe haemorrhagic pancreatitis.

Acute Disease↗
PubMed1992

Paramyosin inhibits complement C1.

We report here the results of studies showing that inhibition of C is a property of several invertebrate paramyosins. Paramyosins from Taenia solium, Schistosoma mansoni, and the mussel Mytilus edulis bind polymeric collagen and can be isolated from crude extracts of tissues by collagen affinity. These paramyosins inhibit C1 function whether the C1 is isolated or present in C2-deficient serum. Because T. solium paramyosin was the best inhibitor, we concentrated further studies on this molecule. T. solium paramyosin binds purified C1q in solution with a dose/response similar to C1r2S2. Further studies of the C1-paramyosin interaction indicate that: 1) C4 is not activated, 2) C4b2a decay is not affected, and 3) there is no effect on the efficiency of C3-9, as provided in EDTA-chelated guinea pig serum, in lysing SRBC. Thus, paramyosin inhibition is directed at the initiation of the classical pathway. The results suggest that paramyosins of helminthic parasites may have a role as modulators of the host immune response through C inhibition at C1.

Animals↗
PubMed2003

Safety and efficacy of pasteurized C1 inhibitor concentrate (Berinert P) in hereditary angioedema: a review. jean.de.serres@aventis.com.

BACKGROUND: Hereditary angioedema caused by C1 inhibitor deficiency can be life threatening. Acute exacerbations are treated with intravenous purified, pasteurized C1 esterase inhibitor concentrate at doses of 500-1000 IU. METHODS: We reviewed the literature about safety and efficacy of the C1 inhibitor concentrate used in Canada (Berinert P) or relevant to it. RESULTS: Post-marketing experience since 1985 is reassuring. There were few adverse events and no transmission of infection with the pasteurized product. A number of case reports, retrospective studies and few randomized or non-randomized prospective studies have shown good efficacy measured as clinical resolution of symptoms or in time to resolution, time to relief or time to improvement. CONCLUSIONS: There are numerous observational studies showing good efficacy and safety and a long post-marketing experience although few randomized placebo-controlled trials.

Angioedema↗
PubMed1998

Acquired angio-oedema caused by IgA paraprotein.

The syndrome of acquired angio-oedema is characterized by late onset of recurrent bouts of angio-oedema or abdominal pain and may be caused by an acquired deficiency of C1-inhibitor (C1-INH), the inhibitor of the first component of complement. Acquired C1-INH deficiency has been described in approximately 50 patients and is strongly associated with malignant B-cell proliferations. We describe a patient with an 8-year history of recurrent abdominal symptoms and angio-oedema with acquired C1-INH deficiency, caused by the presence of IgA-kappa antibodies that inactivate C1-INH. Analysis of the bone marrow revealed an IgA-kappa monoclonal population of plasma cells, without evidence of overt myeloma. Angio-oedema caused by an autoantibody of the IgA isotype is extremely rare and has never been described in a Dutch patient. Recognition of angio-oedema, both hereditary and acquired, is important because of the therapeutic consequences, as will be discussed.

Abdominal Pain↗
PubMed1999

Hereditary angioedema with gastrointestinal involvement: endoscopic appearance.

We present the first reported case of hereditary angioedema (HAE) with gastric involvement to be successfully evaluated by endoscopy both during and after an attack. A 31-year-old man who had a family history of angioedema was admitted to our hospital with complaints of abdominal pain and swelling of extremities. Computed tomography scan and endoscopy carried out during this attack revealed transient gastrointestinal wall edema which, along with decreased levels of serum C4 and C1 inhibitor, confirmed the diagnosis of HAE with gastrointestinal involvement. During the attack, the gastric mucosa was erythematous and edematous, and parts of its surface bulged into the gastric lumen, resembling a submucosal tumor, as a result of massive submucosal edema. During the healing process, a number of small nodules and raised erosions developed over the entire gastric mucosal surface after healing of prominent gastric edema. Within 55 days, the gastric mucosa had returned to normal. The endoscopic findings for the stomach in HAE have not, to our knowledge, been previously described.

Adult↗
PubMed1987

C1q inhibits the expression of B lymphoblastoid cell line interleukin 1 (IL 1).

Although the existence and ubiquity of the C1q receptor is well established, its role in health and disease is largely unknown. Interleukin 1 (IL 1) is the major immunoregulatory molecule produced by macrophages and B lymphoblastoid cell lines. In this paper we present evidence that occupancy of C1q receptors by C1q on B lymphoblastoid cell lines inhibits "IL 1-like" activity, which is constitutively produced by these cells. When 5 X 10(6) Raji cells were cultured (24 hr at 37 degrees C) in the presence or absence of various concentrations of C1q (final concentration; 5 to 50 micrograms/ml) and the cellfree supernatants were analyzed for their effect on thymocyte proliferation by using the concanavalin A co-mitogenesis assay for IL 1, a statistically significant dose-dependent reduction of 3H-TdR incorporation was observed. Similar results were obtained when Daudi and Wil2WT cells were used, whereas Molt4, which is a T cell lymphoblastoid cell line, neither produced "IL 1-like" activity nor was affected by C1q. When immune complex-bound C1q was used instead of free C1q, inhibition of B cell IL 1 activity was also observed. Mixing experiments showed that Raji cells incubated with C1q released an inhibitor of IL 1-induced thymocyte proliferation. C1q alone had no effect on thymocyte proliferation in the presence or absence of human IL 1. In addition, the effect of C1q on IL 1 activity was abrogated either when the C1q was heat inactivated (56 degrees C, 60 min) or when the C1q was incubated with the cells in the presence of F(ab')2 anti-C1q. On the basis of these data, it is concluded that B cell receptor-bound C1q may play an important role in immunoregulation.

Antigen-Antibody Complex↗
PubMed1989

Autoantibody facilitated cleavage of C1-inhibitor in autoimmune angioedema.

C1-inhibitor (C1-Inh) is an important inhibitor of the inflammatory response and deficiency of this inhibitor, which may be hereditary or acquired, is associated with recurrent episodes of edema. Recently, an autoimmune form of angioedema has been described that is associated with functional deficiency of C1-Inh and an autoantibody that impedes C1-Inh function. In this report we describe the isolation of C1-Inh from the monocytes and plasma of a patient with autoimmune angioedema and demonstrate that the patient's monocytes secrete structurally and functionally normal C1-Inh, but show that this protein circulates in the patient's plasma in an inactive, structurally altered form. Furthermore, using analytic gel electrophoresis techniques it is demonstrated that the patient's autoantibody facilitates cleavage of normal C1-Inh, by its target proteases, to the same species of C1-Inh that is found circulating in the patient's plasma. This autoantibody facilitated cleavage of normal C1-Inh is apparently a consequence of destabilization of protease/inhibitor complexes. These findings contribute to our understanding of protease/C1-Inh interactions and document important observations on pathogenic mechanisms in autoimmune disease.

Angioedema↗
PubMedDate not supplied

Hereditary angioedema type II--a study of two families.

Hereditary angioedema (HA) is caused by a quantitative or qualitative deficiency of C1 esterase inhibitor (C1 INH). We present a study of nine patients with HA belonging to two different families. The symptoms started before 10 years of age in most cases (78%). Facial edema (lips, eyes) and of the extremities (feet, hands) were the most frequent complaints. Three patients presented edema of the glottis and one of them underwent a tracheostomy twice. Laboratory tests, outside the acute crisis, revealed low levels of C4 in all patients. The serum levels of C1 INH were normal in seven patients; however, functional activity was not observed in any of them. After the use of a modified androgen (danazol), control of symptoms was observed in all patients, although functional activity was re-established in only five patients.

Adolescent↗
PubMed1989

Synthesis and expression of C1 inhibitor by human umbilical vein endothelial cells.

The biologic activity of C1 esterase, activated forms of factor XII and kallikrein at sites of vascular inflammation may be regulated by C1 inhibitor (C1 INH) elaborated by endothelial cells. Therefore, we investigated whether human umbilical vein endothelial cells (HUVEC) in culture produce C1 INH. Passaged HUVEC contain 1.6 +/- 0.8 micrograms of C1 INH/10(8) cells (mean +/- S.D.; n = 7) which was immunochemically similar to plasma C1 INH measured by a competitive enzyme-linked immunosorbent assay. Methylamine-treated lysates of HUVEC contained a functional inhibitor of purified kallikrein (2.7 +/- 0.8 micrograms activity/10(8) cells, mean +/- S.D.; n = 4). The HUVEC-derived kallikrein inhibitory activity was mostly C1 INH because it was reversed by chemically treating the lysate with chloroform and was neutralized by anti-C1 INH antibody. A lysate of HUVEC derived from an umbilical cord from a patient with Type I hereditary angioedema contained less than 30% of the normal levels of C1 INH antigen and activity. Immunohistochemical staining of HUVEC demonstrated a diffuse pattern of staining for C1 INH. HUVEC C1 INH was also expressed on the endothelial cell surface as detected by binding of anti-C1 INH antibody to intact monolayers and was elaborated progressively into the overlying media over the first 24 h in culture. HUVEC incubated with [35S] methionine secreted a metabolically labeled protein having a molecular mass of 92 kDa immunoisolated using polyclonal or monoclonal antibodies to human C1 INH. A mRNA transcript encoding for C1 INH was detected by slot blot hybridization. Incubation of HUVEC with gamma-interferon stimulated the expression of the 2.1 kilobase mRNA for C1 INH and increased the level of C1 INH produced by these cells. Production and expression of C1 INH by endothelial cells may help modulate the complement system and the contact system of plasma proteolysis on the vascular surface in vivo.

Blotting, Northern↗