RESUMO
Because of its capacity to increase a physiologic inflammatory response, to stimulate phagocytosis, to promote cell lysis and to enhance pathogen immunogenicity, the complement system is a crucial component of both the innate and adaptive immune responses. However, many infectious agents resist the activation of this system by expressing or secreting proteins with a role as complement regulatory, mainly inhibitory, proteins. Trypanosoma cruzi, the causal agent of Chagas disease, a reemerging microbial ailment, possesses several virulence factors with capacity to inhibit complement at different stages of activation. T. cruzi calreticulin (TcCalr) is a highly-conserved, endoplasmic reticulum-resident chaperone that the parasite translocates to the extracellular environment, where it exerts a variety of functions. Among these functions, TcCalr binds C1, MBL and ficolins, thus inhibiting the classical and lectin pathways of complement at their earliest stages of activation. Moreover, the TcCalr/C1 interaction also mediates infectivity by mimicking a strategy used by apoptotic cells for their removal. More recently, it has been determined that these Calr strategies are also used by a variety of other parasites. In addition, as reviewed elsewhere, TcCalr inhibits angiogenesis, promotes wound healing and reduces tumor growth. Complement C1 is also involved in some of these properties. Knowledge on the role of virulence factors, such as TcCalr, and their interactions with complement components in host-parasite interactions, may lead toward the description of new anti-parasite therapies and prophylaxis.
Assuntos
Calreticulina/imunologia , Complemento C1/imunologia , Interações Hospedeiro-Parasita/imunologia , Parasitos/patogenicidade , Animais , Ativação do Complemento , Humanos , Evasão da Resposta Imune , Parasitos/imunologia , Trypanosoma cruzi/imunologia , Trypanosoma cruzi/patogenicidade , Fatores de Virulência/imunologiaRESUMO
Leptospirosis is an important zoonosis of global importance caused by bacteria Leptospira spp. Pathogenic Leptospira is resistant to Complement System killing while non-pathogenic Leptospira is rapidly killed by exposure to normal human serum (NHS). Pathogenic Leptospira interact with Complement Regulators such as Factor H, C4b binding protein and Vitronectin avoiding Complement activation and killing by Alternative and Classical Pathways. One important regulator is C1-inhibitor (C1INH) that interacts with C1s or MASPs controlling the cleavage of C4 and C2 molecules, thereby inhibiting the activation of the Classical and Lectin Pathways. In this study, we demonstrate that attenuated, saprophytic and pathogenic Leptospira interact with C1INH that maintain its regulatory capacity of interaction with C1s preventing the activation of Complement system. Although the interaction with C1INH is not crucial for pathogenic Leptospira survival, it seems to be important for the survival of attenuated and saprophytic Leptospira in normal human serum.
Assuntos
Proteína Inibidora do Complemento C1/metabolismo , Complemento C1/metabolismo , Leptospiraceae/imunologia , Leptospirose/imunologia , Animais , Ativação do Complemento , Proteína Inibidora do Complemento C1/genética , Proteína de Ligação ao Complemento C4b/metabolismo , Fator H do Complemento/metabolismo , Cadeia Alimentar , Humanos , Evasão da Resposta Imune , Leptospiraceae/patogenicidade , Vacinas Atenuadas , Virulência , Vitronectina/metabolismo , ZoonosesRESUMO
Triatoma infestans is an important hematophagous vector of Chagas disease, a neglected chronic illness affecting approximately 6 million people in Latin America. Hematophagous insects possess several molecules in their saliva that counteract host defensive responses. Calreticulin (CRT), a multifunctional protein secreted in saliva, contributes to the feeding process in some insects. Human CRT (HuCRT) and Trypanosoma cruzi CRT (TcCRT) inhibit the classical pathway of complement activation, mainly by interacting through their central S domain with complement component C1. In previous studies, we have detected CRT in salivary gland extracts from T. infestans We have called this molecule TiCRT. Given that the S domain is responsible for C1 binding, we have tested its role in the classical pathway of complement activation in vertebrate blood. We have cloned and characterized the complete nucleotide sequence of CRT from T. infestans, and expressed its S domain. As expected, this S domain binds to human C1 and, as a consequence, it inhibits the classical pathway of complement, at its earliest stage of activation, namely the generation of C4b. Possibly, the presence of TiCRT in the salivary gland represents an evolutionary adaptation in hematophagous insects to control a potential activation of complement proteins, present in the massive blood meal that they ingest, with deleterious consequences at least on the anterior digestive tract of these insects.
Assuntos
Calreticulina/genética , Proteínas do Sistema Complemento/imunologia , Interações Hospedeiro-Parasita/genética , Triatoma/genética , Animais , Galinhas/parasitologia , Clonagem Molecular , Complemento C1/imunologia , Expressão Gênica , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
Blood-feeding insects inject potent salivary components including complement inhibitors into their host's skin to acquire a blood meal. Sand fly saliva was shown to inhibit the classical pathway of complement; however, the molecular identity of the inhibitor remains unknown. Here, we identified SALO as the classical pathway complement inhibitor. SALO, an 11 kDa protein, has no homology to proteins of any other organism apart from New World sand flies. rSALO anti-complement activity has the same chromatographic properties as the Lu. longipalpis salivary gland homogenate (SGH)counterparts and anti-rSALO antibodies blocked the classical pathway complement activity of rSALO and SGH. Both rSALO and SGH inhibited C4b deposition and cleavage of C4. rSALO, however, did not inhibit the protease activity of C1s nor the enzymatic activity of factor Xa, uPA, thrombin, kallikrein, trypsin and plasmin. Importantly, rSALO did not inhibit the alternative or the lectin pathway of complement. In conclusion our data shows that SALO is a specific classical pathway complement inhibitor present in the saliva of Lu. longipalpis. Importantly, due to its small size and specificity, SALO may offer a therapeutic alternative for complement classical pathway-mediated pathogenic effects in human diseases.
Assuntos
Inativadores do Complemento/farmacologia , Via Clássica do Complemento/efeitos dos fármacos , Proteínas de Insetos/farmacologia , Psychodidae/imunologia , Psychodidae/metabolismo , Saliva/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Ativação do Complemento/efeitos dos fármacos , Complemento C1/antagonistas & inibidores , Complemento C1/imunologia , Complemento C1/metabolismo , Complemento C4/antagonistas & inibidores , Complemento C4/imunologia , Complemento C4/metabolismo , Humanos , Proteínas Recombinantes/farmacologiaRESUMO
Schizophrenia (SZ) and bipolar disorder (BD) are severe psychiatric conditions with a neurodevelopmental component. Genetic findings indicate the existence of an overlap in genetic susceptibility across the disorders. Also, image studies provide evidence for a shared neurobiological basis, contributing to a dimensional diagnostic approach. This study aimed to identify the molecular mechanisms that differentiate SZ and BD patients from health controls but also that distinguish both from health individuals. Comparison of gene expression profiling in post-mortem brains of both disorders and health controls (30 cases), followed by a further comparison between 29 BD and 29 SZ revealed 28 differentially expressed genes. These genes were used in co-expression analysesthat revealed the pairs CCR1/SERPINA1, CCR5/HCST, C1QA/CD68, CCR5/S100A11 and SERPINA1/TLR1 as presenting the most significant difference in co-expression between SZ and BD. Next, a protein-protein interaction (PPI) network using the 28 differentially expressed genes as seeds revealed CASP4, TYROBP, CCR1, SERPINA1, CCR5 and C1QA as having a central role in the diseases manifestation. Both co-expression and network topological analyses pointed to genes related to microglia functions. Based on this data, we suggest that differences between SZ and BP are due to genes involved with response to stimulus, defense response, immune system process and response to stress biological processes, all having a role in the communication of environmental factors to the cells and associated to microglia.
Assuntos
Transtorno Bipolar/imunologia , Expressão Gênica/genética , Imunidade Inata/genética , Esquizofrenia/imunologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Transtorno Bipolar/genética , Transtorno Bipolar/patologia , Encéfalo/metabolismo , Caspases Iniciadoras/genética , Complemento C1/genética , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes/genética , Humanos , Modelos Lineares , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Receptores CCR1/genética , Receptores CCR5/genética , Esquizofrenia/genética , Esquizofrenia/patologia , alfa 1-Antitripsina/genéticaRESUMO
In Trypanosoma cruzi, calreticulin (TcCRT) translocates from the endoplasmic reticulum (ER) to the area of flagellum emergence. We propose herein that the parasite uses this molecule to capture complement C1, in an infective apoptotic mimicry strategy. Thus, TcCRT/C1 interactions, besides inhibiting the classical pathway of complement activation as previously shown in our laboratories, will also promote infectivity. This fact correlates with significant increases in TcCRT mRNA levels during early infection stages of a VERO cell line. In vitro, the collagenous and globular C1q domains simultaneously bind TcCRT and antigen aggregated Igs, respectively. Accordingly, mouse immunizations with TcCRT induced humoral responses that, after challenge, correlated with increased parasitemia. Thus, on the parasite surface, whole Igs anti-TcCRT promote C1 deposits on trypomastigotes while, as expected, F(ab')2 fragments decrease it. Likewise, pretreatment of the parasites with whole anti-TcCRT antibodies augmented parasitemia and mortality in mice. In contrast, pretreatment with F(ab')2 fragments anti-TcCRT, devoid of their capacity to provide additional C1q binding sites, was protective. Most important, while pretreatment of trypomastigotes with C1q increased infectivity in the RAW murine cell line, as well as mice mortality and parasitemia, the F(ab')2 fragments significantly interfered with the C1q-dependent infectivity. Differently from other surface molecules involved in infectivity, TcCRT uses C1 as an adaptor molecule to recognize host cells. As expected, since TcCRT is one of several cell surface parasite molecules participating in infectivity, attempts to interfere with the C1/TcCRT interactions with F(ab')2 fragments, were moderately but significantly effective, both in vitro and in vivo.
Assuntos
Complemento C1/metabolismo , Macrófagos/metabolismo , Trypanosoma cruzi/fisiologia , Animais , Complexo Antígeno-Anticorpo/metabolismo , Antígenos de Protozoários/imunologia , Calreticulina/imunologia , Linhagem Celular , Doença de Chagas , Complemento C1/imunologia , Imunidade Humoral , Imunização , Macrófagos/imunologia , Macrófagos/parasitologia , Macrófagos/patologia , Camundongos , Parasitemia , Ligação Proteica/imunologia , Trypanosoma cruzi/patogenicidade , VirulênciaRESUMO
Hereditary (HAE) and acquired (AAE) angioedema are vascular reactions involving the sub mucosal tissues, representing localized edema caused by dilatation and increased permeability of the capillaries. HAE and AAE are clinical disorders characterized by angioedema that require prompt differentiation from other causes of angioedema in order to receive the most pertinent and effective therapeutic interventions. The aim of this report is to describe the clinical characteristics of patients with both HAE and AAE identified and followed at the Immunology Clinic of the University Hospital at the Puerto Rico Medical Center, their response and side effects to danazol therapy and their comparison with other series of similar patients reported in the literature. Overall, the patients in this sample presented a similar clinical profile compared to other reported series in the literature.
Assuntos
Angioedema , Adolescente , Adulto , Idoso , Angioedema/diagnóstico , Angioedema/tratamento farmacológico , Angioedema/genética , Angioedema/imunologia , Criança , Complemento C1/análise , Complemento C1q/análise , Complemento C4/análise , Proteínas Inativadoras do Complemento/análise , Danazol/administração & dosagem , Danazol/efeitos adversos , Danazol/uso terapêutico , Interpretação Estatística de Dados , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Antagonistas de Estrogênios/administração & dosagem , Antagonistas de Estrogênios/efeitos adversos , Antagonistas de Estrogênios/uso terapêutico , Feminino , Humanos , Imunodifusão , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
Dermatan sulfate (DS) is a member of the family of structurally complex, sulfated, linear heteropolysaccharides called glycosaminoglycans (GAGs). It has a similar structure to heparin and heparan sulfate (HS), but with acetylgalactosamine replacing glucosamine, and the uronic acid moiety, mainly iduronic, joined 1-->3 to the hexosamine. We are studying the relationships between structure and activities of dermatan sulfate, in particular those associated with the thrombin inhibition mediated by heparin cofactor II (HCII). As we have demonstrated with heparin, a small fraction of dermatan sulfate was isolated by precipitation with the first component of the complement system, under very specific conditions of low ionic strength, and the presence of calcium ions. The sulfate content and the anticoagulant activity of the dermatan sulfate fraction isolated in the precipitate were three and four times greater respectively than the starting material. Our in vivo studies showed that this fraction has threefold higher thrombolytic activity than the DS. All these results suggest that this fraction could be used as a therapeutic agent for thrombi dissolution.
Assuntos
Anticoagulantes/química , Anticoagulantes/farmacologia , Complemento C1/metabolismo , Dermatan Sulfato/química , Dermatan Sulfato/farmacologia , Acetilgalactosamina/química , Animais , Anticoagulantes/isolamento & purificação , Anticoagulantes/metabolismo , Cálcio/química , Precipitação Química , Complemento C1/química , Complemento C1/isolamento & purificação , Dermatan Sulfato/isolamento & purificação , Dermatan Sulfato/metabolismo , Fibrinolíticos/farmacologia , Hexosaminas/química , Ácido Idurônico/química , Masculino , Concentração Osmolar , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Sulfatos/químicaRESUMO
Hereditary (HAE) and acquired (AAE) angioedema are vascular reactions involving the sub mucosal tissues, representing localized edema caused by dilatation and increased permeability of the capillaries. HAE and AAE are clinical disorders characterized by angioedema that require prompt differentiation from other causes of angioedema in order to receive the most pertinent and effective therapeutic interventions. The aim of this report is to describe the clinical characteristics of patients with both HAE and AAE identified and followed at the Immunology Clinic of the University Hospital at the Puerto Rico Medical Center, their response and side effects to danazol therapy and their comparison with other series of similar patients reported in the literature. Overall, the patients in this sample presented a similar clinical profile compared to other reported series in the literature.
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Angioedema , Antagonistas de Estrogênios/administração & dosagem , Antagonistas de Estrogênios/efeitos adversos , Antagonistas de Estrogênios/uso terapêutico , Complemento C1 , Complemento C1q , Complemento C4 , Interpretação Estatística de Dados , Diagnóstico Diferencial , Danazol/administração & dosagem , Danazol/efeitos adversos , Danazol/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Imunodifusão , Inativadores do Complemento/análise , Fatores de TempoRESUMO
La heparina inhibe la coagulación uniéndose a la antitrombina y aumentando miles de veces la velocidad con que esa glicoproteína inhibe la trombina. Otra de las importantes actividades biológicas de la heparina es inhibir el sistema del complemento humano. Los resultados obtenidos por distintos autores indican que estas dos actividades, anticoagulante y anticomplementaria, residen en distintos segmentos de la heparina. El objetivo de esta investigacion fue estudiar como pueden reconocerse las macromoléculas tan diferentes que intervienen en ambos procesos. Se utilizó un sistema sencillo constituido por la heparina y la lectina Concanavalina A. Se logró precipitar de la heparina la fracción activa que posee alta afinidad por la antitrombina y gran actividad anticoagulante. Fueron imprescindibles condiciones experimentales muy específicas de baja fuerza iónica y la presencia de iones calcio. Los experimentos se extendieron a un sistema fisiológico reemplazando la Concanavalina A por el primer componente del sistema del complemento humano, el complejo proteico C1. Se comprobó que manteniendo las condiciones experimentales anteriores se aislaba en el precipitado de la interacción con el C1 una subpoblación de la heparina con gran afinidad por la antitrombina y muy alta actividad anticoagulante. Se concluye que el complejo proteico C1 reconoció en la heparina la fracción activa de la misma donde se encuentra el segmento de gran afinidad por la antitrombina
Assuntos
Humanos , Antitrombinas , Complemento C1 , Concanavalina A , Glicosaminoglicanos , Heparina , Técnicas In Vitro , Anticoagulantes , Técnicas de Laboratório Clínico , Proteínas do Sistema Complemento , Heparina , Heparina de Baixo Peso Molecular , Modelos MolecularesRESUMO
La heparina inhibe la coagulación uniéndose a la antitrombina y aumentando miles de veces la velocidad con que esa glicoproteína inhibe la trombina. Otra de las importantes actividades biológicas de la heparina es inhibir el sistema del complemento humano. Los resultados obtenidos por distintos autores indican que estas dos actividades, anticoagulante y anticomplementaria, residen en distintos segmentos de la heparina. El objetivo de esta investigacion fue estudiar como pueden reconocerse las macromoléculas tan diferentes que intervienen en ambos procesos. Se utilizó un sistema sencillo constituido por la heparina y la lectina Concanavalina A. Se logró precipitar de la heparina la fracción activa que posee alta afinidad por la antitrombina y gran actividad anticoagulante. Fueron imprescindibles condiciones experimentales muy específicas de baja fuerza iónica y la presencia de iones calcio. Los experimentos se extendieron a un sistema fisiológico reemplazando la Concanavalina A por el primer componente del sistema del complemento humano, el complejo proteico C1. Se comprobó que manteniendo las condiciones experimentales anteriores se aislaba en el precipitado de la interacción con el C1 una subpoblación de la heparina con gran afinidad por la antitrombina y muy alta actividad anticoagulante. Se concluye que el complejo proteico C1 reconoció en la heparina la fracción activa de la misma donde se encuentra el segmento de gran afinidad por la antitrombina (AU)
Assuntos
Humanos , Técnicas In Vitro , Heparina/fisiologia , Antitrombinas/fisiologia , Complemento C1/fisiologia , Concanavalina A , Glicosaminoglicanos , Heparina/isolamento & purificação , Proteínas do Sistema Complemento , Técnicas de Laboratório Clínico , Heparina de Baixo Peso Molecular , Anticoagulantes , Modelos MolecularesRESUMO
Antithrombin (AT) high affinity of unfractionated heparin (UFH) resides in a specific pentasaccharide sequence. Heparin also regulates complement activity on the classical and the alternative pathways. Most experimental pieces of evidence accumulated show that these important activities reside in different segments of the heparin molecule. We demonstrated in previous papers that a low ionic strength and the presence of calcium ions are essential to detect specific interactions between glycosaminoglycans and proteins. Then these very strict conditions were used, and we demonstrated that the first protein complex of the human complement cascade recognizes in the UFH a fraction with very high anticoagulant activity. After isolation from the precipitate of the interaction, this fraction of heparin also contained the pentasaccharide sequence responsible for the great affinity with AT: in fact, it was strongly bound to a resin of AT agarose, and to detach it, an ionic strength of 0.6 M sodium chloride was required. In this way, the heparin regions responsible for the anticoagulant activity and also for the effects over the complement system were identified on the same short segment of the heparin molecule, which includes the active fraction of the glycosaminoglycan. The differences with early results could be explained by our experimental conditions of low ionic strength and the presence of calcium ions used for the interaction of the protein and the glycosaminoglycan.
Assuntos
Antitrombina III/metabolismo , Complemento C1/metabolismo , Heparina/metabolismo , Anticoagulantes/isolamento & purificação , Anticoagulantes/metabolismo , Anticoagulantes/farmacologia , Sítios de Ligação , Cálcio , Precipitação Química , Cromatografia de Afinidade , Heparina/isolamento & purificação , Heparina/farmacologia , Humanos , Concentração Osmolar , Ligação ProteicaRESUMO
Heparin is a natural glycosaminoglycan with chains consisting of alternating 1-4 linked residues of sulphated uronic acids (L-iduronic in great proportion) and D- glucosamine attached to a serine-glycine linear protein core. In our previous experiments with a low molecular weight heparin (Mr = 4.000 to 6.000) obtained by partial chemical degradation of the original heparin we could concentrate its anticoagulant activity by precipitation with the first component of the human complement system. In order to confirm these results with a more physiological unfractionated heparin we used commercial heparin from porcine intestinal mucose with a high molecular weight (9.000-15.000) and a specific activity of 179 U/mg. An heparin fraction with high anticoagulant activity was isolated from the precipitate of the interaction between this high molecular weight heparin isolated from a natural source, and the first component of the human complement system. Our results confirmed, in opposition to almost all early literature, that under very strict conditions of pH 6.0, calcium chloride concentration (2 mM), and very low ionic strength (25 mM), the first component of the human complement cascade recognize heparin fractions "enriched" in the high affinity sequence for the antithrombin III.
Assuntos
Complemento C1/metabolismo , Heparina/metabolismo , Animais , Antitrombina III/metabolismo , Cálcio/metabolismo , Heparina/química , Heparina/isolamento & purificação , Humanos , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Mucosa Intestinal/química , Peso Molecular , SuínosRESUMO
We investigated the in vitro action of the bile pigments, unconjugated bilirubin (UB) and bilirubin monoglucuronide (BMG) on complement (C) cascade reaction. Both UB and BMG inhibited hemolysis in the classical pathway (CP) in a dose-dependent manner at low micromolar concentrations, UB showing a stronger effect than BMG. The analysis of the action of UB on the hemolytic activity of the C1, C4, C2 and C-EDTA components of the C cascade revealed that the C1 step was the most inhibited. An enzyme immunoassay was developed to evaluate the effect of UB on the binding of C1q, one of the subcomponents of C1, to human IgM and IgG. The study demonstrated that the unconjugated pigment interferes both the C1q-IgM and -IgG interactions, thus tentatively explaining the inhibitory action of UB on hemolytic activity of C1. We conclude that the anti-complement effect of UB is mainly exerted on the C1 component, the recognition unit of CP. The potential clinical implication of the reported effects in hyperbilirubinemia is discussed.
Assuntos
Bilirrubina/farmacologia , Proteínas Inativadoras do Complemento/farmacologia , Proteínas do Sistema Complemento/imunologia , Hemólise/efeitos dos fármacos , Animais , Bilirrubina/análogos & derivados , Células Cultivadas , Complemento C1/imunologia , Complemento C1q/imunologia , Eritrócitos/efeitos dos fármacos , Humanos , Técnicas Imunoenzimáticas , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , OvinosRESUMO
A low molecular weight heparin fraction with high anticoagulant activity was isolated from the precipitate of the interaction with the first component of the human complement system. Our results confirmed the predictions: under very strict conditions of pH (6.3), CaCl2 concentration (2 mM), ionic strength (25 mM) and protein/heparin ratio (1/1), the first component of the complement recognizes the high antithrombin III affinity fraction of heparin, and allows a concentration of the biological activity of the original low molecular weight-heparin.
Assuntos
Complemento C1/metabolismo , Heparina de Baixo Peso Molecular/metabolismo , Anticoagulantes/metabolismo , Antitrombina III/metabolismo , Complemento C1/química , Complemento C1/isolamento & purificação , Heparina de Baixo Peso Molecular/química , Humanos , Concentração de Íons de Hidrogênio , Modelos Químicos , Concentração OsmolarRESUMO
Allele frequencies for the orosomucoid 1 (ORM1), orosomucoid 2 (ORM2), alpha-2-HS-glycoprotein (AHSG) and complement component I (IF) loci were studied in 393 individuals of three Brazilian Indian tribes. In the ORM1 locus only two alleles were observed among the Urubu-Kaapor, while five were found among the Pacaás Novos. The frequency of ORM1*1 was similar in these two tribes (0.734 and 0.715, respectively) but departed more markedly among the Parakanã (0.870). Variation for ORM2 locus was found among the Pacaás Novos only, with ORM2*3 being observed in just three individuals. A new variant (AHSG*PN) was found in the AHSG system. Frequency for AHSG*1 was unexpectedly low in the three tribes, especially, among the Pacaás Novos, where the prevalence (0.145) is the lowest considering other data reported thus far. For IF locus, variability was also restricted to only one trible (Urubu-Kaapor) and attributed to a new polymorphic allele, IF* A3.
Assuntos
Proteínas Sanguíneas/genética , Complemento C1/genética , Variação Genética , Indígenas Sul-Americanos/genética , Orosomucoide/genética , Alelos , Brasil , Frequência do Gene , Humanos , Focalização Isoelétrica , Polimorfismo Genético , alfa-2-Glicoproteína-HSRESUMO
Sobre 51 pacientes diagnosticados con AEH, se tomaron cuatro pacientes que no hubieron tenido tratamiento androgénico anterior, lo que determino una población heterogénea. Se evaluó el C4, CH50, C1NH funcional y antigénico, CIC (complejos inmunes circulantes), el día uno o basal. Se indica 400 mg/día de Ladogal (Danazol) y se extrae muestra de sangre los días 4, 7, 10, 14, y se mide cada uno de los parámetros iniciales, para valorar los efectos de la droga sobre cada uno de ellos. Al día 14, desaparecen los CIC, se incrementa el C4 y CH50, mientras que el C1NH, antigénico y funcional no varía en forma significativa. Por ello, consideramos que el Ladogal, actúa incrementando el C4 y CH50, aclarando el plasma de CIC y/o enzimas activantes del C1 y Factor Hageman. Simultaneamente estimula la síntesis del C1NH, que no se pone en evidencia, hasta que no desaparezca la activación. Proponemos el esquema de 14 días de 400 mg/día de Ladogal, seguidos de cúatro días de descanso, en pacientes Tipo I y II de AEH
Assuntos
Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , História do Século XX , Angioedema/tratamento farmacológico , Danazol/uso terapêutico , Complexo Antígeno-Anticorpo/imunologia , Complemento C1/efeitos dos fármacos , Complemento C4/efeitos dos fármacosRESUMO
Circulating immune complexes were evaluated in 25 patients (age range 10 to 46 years) who had undergone splenectomy for non-malignant conditions by studying a polyethylene glycol insoluble serum fraction. Although the extent of binding to Clq was within normal limits, these patients had increased concentrations of factor B in the immune complex serum fraction. These findings indicate that an unusual type of circulating immune complex may be detected after splenectomy, suggesting a possible role for the spleen in the removal of circulating immune complexes.
Assuntos
Complexo Antígeno-Anticorpo/metabolismo , Esplenectomia , Adolescente , Adulto , Criança , Enzimas Ativadoras do Complemento/metabolismo , Complemento C1/metabolismo , Complemento C1q , Complemento C3b/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Precipitina , Baço/imunologia , Fatores de TempoRESUMO
Although subcomponents C1r and C1s of the first complement component, C1, have been established to be in the same linkage group as the proline-rich protein gene cluster on chromosome 12p13.2, no direct analysis of linkage between the C1R and C1S structural gene loci has been available. We have detected through a population screening study 5 families which are heterozygous at the structural loci for both C1R and C1S. Three of the 5 families, 21 individuals, were informative for linkage. A maximum lod score of 1.505 at theta = 0.00 was found in a two-point analysis between C1R and C1S. Ten populations were screened for structural variation at the C1S locus. Only US Whites and a Kodiak Island Eskimo group expressed heterogeneity. The frequencies of the designated alleles, C1S*1 and C1S*2, were 0.992 and 0.007, respectively, in the US White population and 0.998 and 0.002, respectively, in the Kodiak Island Eskimo population. In addition, the product of a putative new allele, designated C1S*4, was observed in a single US White individual but segregation of this variant was not observed in the limited family data available.
Assuntos
Proteínas Sanguíneas/genética , Enzimas Ativadoras do Complemento/genética , Complemento C1s/genética , Ligação Genética , Genética Populacional , Complemento C1/genética , Complemento C1r , Feminino , Frequência do Gene , Humanos , Masculino , Linhagem , Fenótipo , Grupos Raciais , Estados UnidosRESUMO
A serum fraction from patients with sickle cell-betao thalassemia prepared by treatment with polyethyleneglycol showed increased amounts of C1q-precipitable immune complexes, i.e., 216 microng/dl (range, 141-266 microng/d) vs 181 microng/dl (range, 152-228 microng/dl) for controls (P<0.05), as well as increased amounts of protein. Levels of IgG, IgA, IgM, C3, C4 and factor B in the same fraction were within the normal range