RESUMO
C3 nephritic factor (NEF), an IgG autoantibody to the alternative pathway C3 convertase, is usually measured by crossed immunoelectrophoresis (CI) but recently a reliable haemolytic assay (HA) was described by Rother (1982). This method is more specific than CI because it is negative in sera with immune complexes, SLE and sera incubated with IgG aggregates. The haemolytic assay is sensitive enough to detect NEF antibody in serum from patients with only slightly low C3 levels and NEF negatives by CI. The haemolytic assay is easy to perform and reproducible, the interassay coefficient of variation being 10.7% compared to 64% in the CI. The intra-assay coefficient of variation in CI was 28% compared to 5.5% in the haemolytic assay. The haemolytic method enabled us to study the kinetic effects of NEF on C3b.Bb bound to sheep erythrocytes, and the lysis mediated by ShE.C3b.Bb.NEF complex. Also the C and NEF binding to sheep erythrocytes was studied.
Assuntos
Fator Nefrítico do Complemento 3/sangue , Proteínas Inativadoras do Complemento/sangue , Animais , Glomerulonefrite/sangue , Hemoglobinometria/métodos , Hemólise , Humanos , Imunoeletroforese Bidimensional/métodos , Cinética , Lúpus Eritematoso Sistêmico/sangue , Ligação ProteicaRESUMO
Serum levels of the C3 nephritic factor (C3NeF), an IgG autoantibody directed against the C3bBb convertase of the alternative complement pathway, and of eight complement components (C1q, C4, C3, C3d, C5, C9, fB and properdin) were measured in 109 serum samples from 27 patients with idiopathic membranoproliferative glomerulonephritis (MPGN) (type I, 20 cases, and type II, 7 cases) and 14 patients with secondary MPGN. Correlations between the concentrations of C3NeF, serum complement levels and progression of the renal damage were studied during the course of the disease in 14 patients with C3NeF activity. The results showed that (1) C3NeF activity was more frequent in patients with type II MPGN than in patients with type I disease; nevertheless there was a high incidence of this splitting activity in patients with secondary MPGN, (2) high levels of the complement components were present in patients with MPGN, (3) low levels of C3 occurred frequently in type II disease and in secondary MPGN, (4) there was no correlation between C3, fB and C3NeF levels, (5) the presence of C3NeF was associated with a more rapid deterioration of renal function. Longitudinal studies showed that serum levels of C3NeF were not satisfactory for monitoring the clinical course of the illness and, in this respect, are similar to the levels of other autoantibodies in patients with autoimmune disease. As MPGN is a clinical syndrome with various pathogeneses, we suggest that the autoantibody, C3NeF, should be considered only as a marker of some forms of MPGN.
Assuntos
Fator Nefrítico do Complemento 3/sangue , Proteínas Inativadoras do Complemento/sangue , Glomerulonefrite/imunologia , Autoanticorpos/análise , Complemento C3/metabolismo , Proteínas do Sistema Complemento/metabolismo , Humanos , Imunoglobulina G/imunologia , Testes de Função Renal , Análise de RegressãoRESUMO
In a 56-year old woman progressive partial lipodystrophy began at the age of 6 years on the face, thereafter extending slowly down to mid-thigh level (fig. 1 and 2), with moderate hypertrophy of the subjacent fatty tissue and a fatty macroglossia (fig. 3). Histological examination of the lipodystrophic skin not only showed an absence of fatty tissue, but also abnormalities at the dermis-epidermis junction with hyaline bodies (fig. 4). At the age of 23 she developed purpura, predominantly on the legs, which rapidly became chronic (fig. 5); histological examination showed leucocytoclasic vasculitis of dermal vessels (fig. 6) with granular deposits of C3 on the vessels and of IgM at the dermis-epidermis junction. Episodes of polyarthralgia and headaches were frequent. Regressive neuritis of the external popliteal nerve occurred when she was 53-year old. Renal function tests proved normal, but renal biopsy was not performed. There was no diabetes mellitus, but an oral glucose tolerance test and a somatostatin insulin glucose test elicited definite resistance to insulin. A search for a serum factor inhibiting insulin receptors was negative. Permanent abnormalities in serum were a very deep fall in C3, a pronounced fall in CH50 and a low C4 level. Besides, a C3 nephritic factor (NeF) at a high level and circulating immune complexes were present (table I); a mixed IgM-IgG cryoglobulin was found intermittently (fig. 7). Clearance of the immune complexes by splenic macrophages was extremely slow. During a series of plasma exchanges, serum C3 increased transiently, whereas serum C4 remained unchanged (fig. 8).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Fator Nefrítico do Complemento 3/sangue , Complemento C3/deficiência , Complemento C4/deficiência , Proteínas Inativadoras do Complemento/sangue , Lipodistrofia/complicações , Púrpura/complicações , Vasculite/complicações , Complexo Antígeno-Anticorpo/metabolismo , Biópsia , Complemento C4/genética , Feminino , Humanos , Hiperinsulinismo/complicações , Lipodistrofia/imunologia , Lipodistrofia/patologia , Pessoa de Meia-Idade , Púrpura/imunologia , Púrpura/patologia , Vasculite/imunologia , Vasculite/patologiaAssuntos
Fator Nefrítico do Complemento 3/sangue , Proteínas Inativadoras do Complemento/sangue , Animais , Bioensaio/métodos , Fator Nefrítico do Complemento 3/isolamento & purificação , Via Alternativa do Complemento , Glomerulonefrite/sangue , Cobaias , Humanos , Imunoeletroforese , Zimosan/farmacologiaRESUMO
The high frequency of meningococcal infections in patients with congenital deficiency of a component of the complement terminal pathway emphasizes the critical role of this system in host resistance against Neisseriaceae. We report the observation of a subacute septicaemia due to N. meningitidis serogroup Y. This girl had an acquired deficit of the C3 fraction of complement due to a high titre of C3 nephritic factor (C3NeF). There was no evidence of partial lipodystrophy or biological symptoms of glomerular disease. The meningococcal infection revealed this biological abnormality.
Assuntos
Complemento C3/deficiência , Infecções Meningocócicas , Sepse/etiologia , Criança , Fator Nefrítico do Complemento 3/sangue , Feminino , HumanosRESUMO
Two teenage patients who presented with meningococcal meningitis were found to have persistently low C3 levels even after recovery. This was accompanied by circulating C3 nephritic factor, which persisted for more than 12 months in each case. Neither patient had evidence of partial lipodystrophy or of glomerulonephritis initially, although one patient subsequently developed mesangioproliferative glomerulonephritis following a second admission with pneumococcal pneumonia. It is possible that the generation of the nephritic factor was initiated during the presenting illness.
Assuntos
Fator Nefrítico do Complemento 3/sangue , Complemento C3/deficiência , Proteínas Inativadoras do Complemento/sangue , Meningite Meningocócica/imunologia , Adolescente , Via Alternativa do Complemento , Feminino , Humanos , MasculinoRESUMO
Advanced renal failure, nephrotic-range proteinuria due to proliferative glomerulonephritis and multiple myeloma with circulating IgG2 lambda and free lambda light-chain paraproteins occurred in a 31-year-old male. Commonly established causes of renal failure in multiple myeloma were excluded. Immunofluorescence revealed heavy granular glomerular deposition of C3. Serum C3 was decreased, and C3c was increased. C3 nephritic-factor (C3 NeF)-like activity was demonstrated in the serum. Plasmapheresis and chemotherapy resulted in a decrease in paraprotein concentration up to 90%, a decrease in C3 NeF-like activity to negligible, normal serum complement levels and a marked improvement in both renal function and proteinuria. With reference to the literature, the possibility of a syndrome of paraproteinemia, C3 NeF-like activity and glomerulonephritis is forwarded.
Assuntos
Fator Nefrítico do Complemento 3/sangue , Proteínas Inativadoras do Complemento/sangue , Glomerulonefrite Membranoproliferativa/sangue , Mieloma Múltiplo/complicações , Adulto , Fator Nefrítico do Complemento 3/análise , Glomerulonefrite Membranoproliferativa/metabolismo , Humanos , Glomérulos Renais/análise , MasculinoRESUMO
A patient with nephritic factor in the serum following an attack of disseminated herpes is described. In the majority of cases, the factor is associated with mesangio-capillary glomerulonephritis, with or without partial lipodystrophy. It has, however, been described in cases of partial lipodystrophy alone, in one patient with recurrent pyogenic infections, and in one healthy individual. It has not previously been described in an individual with disseminated viral infection.
Assuntos
Fator Nefrítico do Complemento 3/sangue , Proteínas Inativadoras do Complemento/sangue , Herpes Simples/sangue , Lipodistrofia/sangue , Adulto , Complexo Antígeno-Anticorpo/análise , Complemento C3/análise , Herpes Simples/fisiopatologia , Humanos , MasculinoRESUMO
Membranoproliferative glomerulonephritis, type II is commonly seen in patients with the rare disorder, partial lipodystrophy. This disease complex, although usually seen in the pediatric or young adult age group, should be considered in older patients with characteristic loss of facial fat and signs and symptoms of nephritis. A case of partial lipodystrophy with membranoproliferative glomerulonephritis, type II in an older patient demonstrates the characteristic ultrastructural renal findings.
Assuntos
Glomerulonefrite/complicações , Lipodistrofia/complicações , Membrana Basal/patologia , Biópsia , Fator Nefrítico do Complemento 3/sangue , Feminino , Glomerulonefrite/patologia , Humanos , Glomérulos Renais/patologia , Pessoa de Meia-IdadeRESUMO
Nephritic factor was detected in an individual whose serum showed a selective decrease in the third component of complement (C3) during and subsequent to an illness resembling disseminated gonococcal infection (DGI). As is characteristic of C3 nephritic factor (C3NeF), its activity was heat stable, was associated with IgG, and enhanced cleavage of normal human serum C3 via the alternative pathway. However, unlike previously reported cases of C3NeF detection in association with glomerulonephritis and/or lipodystrophy, this patient has had no significant disease before or more than 2 years after the apparent DGI. The significance of C3NeF in a healthy individual is unexplained, but this study suggests its occurrence may be more ubiquitous than previously suspected.
Assuntos
Fator Nefrítico do Complemento 3/sangue , Complemento C3/deficiência , Proteínas Inativadoras do Complemento/sangue , Adulto , Complemento C3/análise , Fator Nefrítico do Complemento 3/imunologia , Proteínas do Sistema Complemento/análise , Feminino , Humanos , Imunoglobulina G/imunologiaRESUMO
The mean serum concentrations of C3b inactivator (C3bINA) and beta1H globulin were measured in eighty-six sera (thirty-five membranoproliferative, thirteen membranous, thirty-one focal and seven minimal change) taken from seventy-five patients with histologically diagnosed glomerulonephritis. In none of the four groups of sera did the mean concentrations of both these proteins differ significantly from the mean levels in a group of fifty normal sera. However, in the membranoproliferative group, the mean level of C3bINA, but not beta1H, was significantly lower in the nephritic factor positive than in the nephritic factor negative group. When the eighty-six sera were considered together, serum concentrations of C3bINA and beta1H correlated with levels of C3, factor B, properdin and C4. When the membranoproliferative group was considered separately, C3bINA levels correlated with levels of C3, factor B, properdin and C4 and beta1H correlated with C3 and factor B, but not properdin or C4 in the nephritic factor negative group, but no such correlations were observed in the nephritic factor positive group. The significance of these findings is discussed in the light of current thoughts on the mechanisms of modulation of the alternative pathway.
Assuntos
beta-Globulinas/análise , Ativação do Complemento , Proteínas Inativadoras do Complemento C3b/sangue , Via Alternativa do Complemento , Glomerulonefrite/imunologia , Complemento C3/análise , Fator Nefrítico do Complemento 3/sangue , Complemento C4/análise , Fator B do Complemento/análise , Humanos , Properdina/análiseRESUMO
C3 nephritic factor (C3 NeF) was measured by assessing its capacity to form complex with C3 and B using an enzyme-linked immunosorbent assay (ELISA). Incubation of C3 NeF with normal human serum in the presence of MgEGTA resulted in a dose-dependent increase of C3-B-IgG complex. No complex was formed in EDTA. The C3 NeF titer estimated in this way was in good accordance with those reported previously by other indirect methods.
Assuntos
Fator Nefrítico do Complemento 3/sangue , Proteínas Inativadoras do Complemento/sangue , Complemento C3/imunologia , Ácido Edético/farmacologia , Ácido Egtázico/farmacologia , Ensaio de Imunoadsorção Enzimática , Glomerulonefrite/imunologia , Humanos , Imunoglobulina G/imunologiaRESUMO
Hemolytic complement was found to be absent in the serum of an 11-yr-old girl (R.N.) with meningococcal septicemia. C1, C4, and C2 were slightly decreased, C3 was absent, C5-C9 within the normal range. B levels immunochemically and electrophoretic mobility of B were normal. C3d was greater than 1000% of a pooled EDTA-plasma standard indicating hypercatabolism of C3. On incubation of the patient's serum with normal human serum activation of C3 occurred even in the presence of 0.04 M EDTA. The amount of C3b generated was, however, greater without any chelating agent or in Mg-EGTA. On gel filtration of the serum two protein containing peaks were found to be responsible for activation of C3: the IgG containing peak was able to activate C3 in normal human serum without chelating agents and in Mg-EGTA but not in the presence of EDTA. The IgM-containing peak activated the third component of complement even in the presence of EDTA. The factor responsible for this phenomenon was termed C3 converting factor (C3 CoF). The IgG fraction of the patients serum caused activation of C3 in Mg-EGTA. However, in the presence of EDTA no activation of C3 could be induced even if physiological concentrations of the patients IgG were added to normal human EDTA-plasma. Thus the activity of the patient's IgG did not differ from typical C3 nephritic factor. The decay of C2 in EAC42 intermediates in the presence of the patient's IgG was uninfluenced indicating that it did not carry autoantibody activity against the classical pathway convertase C4b,2a, an activity recently termed NFc.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Enzimas Ativadoras do Complemento/sangue , Fator Nefrítico do Complemento 3/sangue , Convertases de Complemento C3-C5/sangue , Proteínas Inativadoras do Complemento/sangue , Infecções Meningocócicas/imunologia , Sepse/imunologia , Criança , Via Alternativa do Complemento , Proteínas do Sistema Complemento/metabolismo , Feminino , Hemólise , Humanos , Infecções Meningocócicas/sangue , Sepse/sangueRESUMO
A 15-year-old female experienced two systemic infections with N.meningitidis (group C and B) within a two months period. Classical as well as alternative pathway CH50 determinations on the patients serum showed no lysis. All individual complement factor concentrations, except for C3, were found to be within the reference area. Crossed immunoelectrophoretic analysis of C3 revealed no demonstrable native C3. The patient had normal levels of C3c and a markedly elevated C3d concentration. Serum from the patient was found to convert all native C3 in normal sera within 10 minutes at 37 degrees C. The active converting principle, present in the IgG fraction activated C3 in C4-depleted serum, and had a dose dependent stabilizing effect on the EA-C3bBb complex. The isolated factor showing the characteristics of C3 nephritic factor (C3 NeF), was unchanged in the patients serum over a ten months observation period. Circulating immune complexes (IC) could not be demonstrated by a C1q-dependent assay but the patients capacity to solubilize preformed IC in vitro was virtually abolished. The patient had no signs of renal disease or lipodystrophy.