RESUMO
Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by salivary and lacrimal gland dysfunction. Clinical observations and results from animal models of SS support the role of aberrant epithelial cell apoptosis and immune homeostasis loss in the glands as triggering factors for the autoimmune response. Vasoactive intestinal peptide (VIP) promotes potent anti-inflammatory effects in several inflammatory and autoimmune disease models, including the non-obese diabetic (NOD) mouse model of SS. With the knowledge that VIP modulates monocyte function through vasoactive intestinal peptide receptors (VPAC) and that immune homeostasis maintenance depends strongly upon a rapid and immunosuppressant apoptotic cell clearance by monocytes/macrophages, in this study we explored VPAC expression on monocytes from primary SS (pSS) patients and the ability of VIP to modulate apoptotic cell phagocytic function and cytokine profile. Monocytes isolated from individual pSS patients showed an increased expression of VPAC2 subtype of VIP receptors, absent in monocytes from control subjects, with no changes in VPAC1 expression. VPAC2 receptor expression could be induced further with lipopolysaccharide (LPS) in pSS monocytes and VIP inhibited the effect. Moreover, monocytes from pSS patients showed an impaired phagocytosis of apoptotic epithelial cells, as evidenced by reduced engulfment ability and the failure to promote an immunosuppressant cytokine profile. However, VIP neither modulated monocyte/macrophage phagocytic function nor did it reverse their inflammatory profile. We conclude that monocytes from pSS patients express high levels of VPAC2 and display a deficient clearance of apoptotic cells that is not modulated by VIP.
Assuntos
Apoptose , Citofagocitose/genética , Citofagocitose/imunologia , Monócitos/imunologia , Monócitos/metabolismo , Receptores Tipo II de Peptídeo Intestinal Vasoativo/genética , Síndrome de Sjogren/genética , Síndrome de Sjogren/imunologia , Adulto , Idoso , Estudos de Casos e Controles , Citofagocitose/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Lipopolissacarídeos/imunologia , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Receptores de Peptídeo Intestinal Vasoativo , Peptídeo Intestinal Vasoativo/farmacologia , Adulto JovemRESUMO
The audiovestibular system can be affected by an immunologic etiology. The immune-mediated inner ear disease (IMIED) is a syndrome that includes rapidly progressive sensorineural hearing loss, vertigo and tinnitus, which occurs as a primary disorder or complicates certain autoimmune systemic conditions. However, if treated promptly with immunosuppression, the audiological sequel of IMIED may be avoided. We present a 28 year old female patient, who after rhinitis and mioarthralgias developed a vestibular syndrome. A week later she experienced bilateral hearing loss that progressed to deafness in 72 hours. The examination revealed horizontal and torsional nystagmus, a disrupted vestibulo-ocular reflex and vertigo with the positional changes. Laboratory data were normal except for eritrosedimentation rate (75 mm/1 hour). The autoantibodies usually present in rheumatologic autoimmune systemic diseases were negative. The antibodies to the 68-kD antigen found in the inner ear were positive. The chest x-ray and sinus x-ray were normal. The head magnetic resonance imaging with gadolinium and ear computed tomography were normal. Cerebrospinal fluid studies showed normal findings. With the possible diagnosis of IMIED we started early treatment with corticosteroids, with improvement in auditory and vestibular function thereafter. We highlight the early recognition of IMIED as a differential diagnosis in patients with acute bilateral hearing loss, because prompt treatment with immunosuppression might have a positive effect on auditory function recovery.
Assuntos
Doenças Autoimunes/complicações , Perda Auditiva Bilateral/etiologia , Perda Auditiva Neurossensorial/etiologia , Doenças do Labirinto/complicações , Doença Aguda , Adulto , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Diagnóstico Diferencial , Feminino , Perda Auditiva Bilateral/diagnóstico , Perda Auditiva Bilateral/imunologia , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/imunologia , Humanos , Doenças do Labirinto/diagnóstico , Doenças do Labirinto/imunologiaRESUMO
The audiovestibular system can be affected by an immunologic etiology. The immune-mediated inner ear disease (IMIED) is a syndrome that includes rapidly progressive sensorineural hearing loss, vertigo and tinnitus, which occurs as a primary disorder or complicates certain autoimmune systemic conditions. However, if treated promptly with immunosuppression, the audiological sequel of IMIED may be avoided. We present a 28 year old female patient, who after rhinitis and mioarthralgias developed a vestibular syndrome. A week later she experienced bilateral hearing loss that progressed to deafness in 72 hours. The examination revealed horizontal and torsional nystagmus, a disrupted vestibulo-ocular reflex and vertigo with the positional changes. Laboratory data were normal except for eritrosedimentation rate (75 mm/1 hour). The autoantibodies usually present in rheumatologic autoimmune systemic diseases were negative. The antibodies to the 68-kD antigen found in the inner ear were positive. The chest x-ray and sinus x-ray were normal. The head magnetic resonance imaging with gadolinium and ear computed tomography were normal. Cerebrospinal fluid studies showed normal findings. With the possible diagnosis of IMIED we started early treatment with corticosteroids, with improvement in auditory and vestibular function thereafter. We highlight the early recognition of IMIED as a differential diagnosis in patients with acute bilateral hearing loss, because prompt treatment with immunosuppression might have a positive effect on auditory function recovery.
RESUMO
Primary Sjögren Syndrome is a chronic autoimmune disease characterized by exocrine gland dysfunction. Here we present evidence of the activation of nitric oxide signaling cascade by circulating antibodies of patients with Sjögren Syndrome in rat submandibular glands. Constitutive nitric oxide synthase and cyclic GMP levels are modulated by Sjögren IgGs through the activation of muscarinic acetylcholine receptors on the glands. The effects are similar to those produced by the agonist carbachol and blocked by the antagonist atropine. The involvement of M1 subtype of muscarinic receptors is proposed since both a synthetic peptide homologous to an extracellular domain of M1 receptor and pirenzepine, a selective M1 antagonist, partially blocked the effects. We conclude that Sjögren Syndrome antibodies can activate nitric oxide signaling in submandibular glands by interacting with muscarinic acetylcholine receptors.
Assuntos
Autoanticorpos/farmacologia , Óxido Nítrico/metabolismo , Receptores Muscarínicos/imunologia , Receptores Muscarínicos/metabolismo , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/metabolismo , Glândula Submandibular/imunologia , Glândula Submandibular/metabolismo , Adulto , Sequência de Aminoácidos , Animais , Autoanticorpos/sangue , Autoantígenos/genética , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/farmacologia , Pessoa de Meia-Idade , Dados de Sequência Molecular , Ratos , Ratos Wistar , Receptor Muscarínico M1 , Receptores Muscarínicos/genética , Transdução de SinaisRESUMO
OBJECTIVES: To translate into Argentine Spanish and cross-culturally adapt the Childhood Health Assessment Questionnaire (CHAQ) and validate the adapted instrument in Argentine patients with juvenile rheumatoid arthritis (JRA). METHODS: Five bilingual Argentine pediatric rheumatologists translated into Argentine Spanish and cross-culturally adapted the United States English CHAQ. Pretesting was done in a sample of 23 parents using a probe question technique. Parents of 70 patients with JRA and 21 healthy children (controls) participated in the validation phase. All were from Argentina. RESULTS: The mean disability index (DI) scores for patients with systemic, polyarticular, or pauciarticular onset JRA were 0.64, 0.32, and 0.1, respectively. Healthy controls averaged 0.2. Intercomponent correlations were between 0.4 and 0.9, suggesting internal consistency, but also some redundancy. Test-retest reliability, studied at a 1-week interval, was moderate (mean DI 0.44 [in clinic] and 0.29 [one week later], Pearson's correlation = 0.82). We compared CHAQ scores from 15 parents with those of their children > 10 years of age. Significantly higher DI scores were given by patients than their respective parents (P > 0.019), but the pairwise scores (parent-patient) were highly correlated (r = 0.986). CONCLUSIONS: Cross-cultural adaptation of the US CHAQ to Argentina required few changes. Although DI scores for all patient subgroups were higher than for controls subjects, the scores were low, particularly for those with pauciarticular disease. Prospective studies designed to examine the sensitivity to change and predictive validity will help to assess further the usefulness of the adapted CHAQ in the Argentine population.
Assuntos
Atividades Cotidianas , Artrite Juvenil/etnologia , Artrite Juvenil/fisiopatologia , Pessoas com Deficiência/classificação , Nível de Saúde , Inquéritos e Questionários/normas , Tradução , Adolescente , Argentina , Estudos de Casos e Controles , Criança , Pré-Escolar , Comparação Transcultural , Humanos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Estados UnidosRESUMO
PURPOSE: The authors demonstrated that immunoglobulin G, present in the sera of patients with primary Sjögren syndrome (pSS), could recognize and activate muscarinic acetylcholine receptors (mAChRs) of rat exorbital acrimal gland. METHODS: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting, and radioligand binding and biologic assays were used to demonstrate autoantibodies against mAChRs. RESULTS: These autoantibodies recognized by means of SDS-PAGE and immunoblotting assay a band of approximately 70 kDa expressed on lacrimal gland membranes that comigrated with the peak of labeled mAChRs. Moreover, pSS IgG were able to inhibit, in an irreversible manner, the binding of [3H]quinuclidinyl benzilate to mAChRs of rat exorbital lacrimal glands and to simulate the biologic effect of mAChR agonists, because they trigger the activation of phosphoinositide turnover. Atropine and 4-diphenylacetoxy-N-methylpiperidine methiodide blocked the effect and carbachol mimicked it, confirming that the M3 subtype mAChRs mediated pSS IgG action. As control, IgG from sera of women without pSS gave negative results on immunoblotting, binding, and biologic assays, thus demonstrating the specificity of the reaction. CONCLUSIONS: Autoantibodies against mAChRs may be considered among the serum factors implicated in the pathophysiology of the development of pSS dry eyes.
Assuntos
Autoanticorpos/análise , Aparelho Lacrimal/imunologia , Receptores Muscarínicos/imunologia , Síndrome de Sjogren/imunologia , Adulto , Animais , Ligação Competitiva/efeitos dos fármacos , Relação Dose-Resposta a Droga , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Immunoblotting , Imunoglobulina G/análise , Aparelho Lacrimal/efeitos dos fármacos , Antagonistas Muscarínicos/metabolismo , Antagonistas Muscarínicos/farmacologia , Fosfatidilinositóis/metabolismo , Quinuclidinil Benzilato/metabolismo , Ensaio Radioligante , Ratos , Ratos Wistar , Receptor Muscarínico M3 , Receptores Muscarínicos/metabolismoRESUMO
A young girl born to a mother with systemic lupus erythematosus (SLE) had congenital heart block and developed symptoms of a connective tissue disorder at the age of 13 y. When first seen at the age of 15 y she was found to have an unclassified connective tissue disorder and to be seropositive for anti Ro/SSA and U1 RNP. This constellation of clinical/serological features has not been described among the reported handful of patients with congenital heart block and subsequent development of a connective tissue disorder.
Assuntos
Anticorpos Antinucleares/imunologia , Doenças Autoimunes/genética , Doenças do Tecido Conjuntivo/genética , Bloqueio Cardíaco/congênito , RNA Citoplasmático Pequeno , Adolescente , Adulto , Anticorpos Antinucleares/sangue , Autoantígenos/imunologia , Doenças Autoimunes/imunologia , Doenças do Tecido Conjuntivo/imunologia , Feminino , Antígenos HLA/análise , Bloqueio Cardíaco/imunologia , Humanos , Imunidade Materno-Adquirida , Lúpus Eritematoso Sistêmico/genética , Gravidez , Complicações na Gravidez/imunologia , Doença de Raynaud/etiologia , Ribonucleoproteína Nuclear Pequena U1/imunologia , Ribonucleoproteínas/imunologia , Esclerodermia Localizada/etiologiaRESUMO
An 8-year-old girl with juvenile dermatomyositis (DM) developed dystrophic calcifications 26 months after diagnosis. She also had severe steroid induced bone loss (osteoporosis). The calcifications turned into generalized heterotopic calcinosis with an exoskeleton-like pattern, despite successful treatment of her myopathy with methylprednisolone and immunosuppressive drugs. She was subsequently treated with oral diltiazem (5 mg/kg/day) to control calcinosis and oral pamidronate (4 mg/kg/day) in addition to calcium and vitamin D supplementation, which she had been taking for 3 years. After 21 months of treatment, clinical and radiological examination revealed dramatic regression of the calcinosis. Bone mass reached normal levels, as determined by bone absorptiometry. Diltiazem alone or in combination with other drugs could be a useful therapy in patients with juvenile DM and pronounced calcifications.
Assuntos
Calcinose/tratamento farmacológico , Dermatomiosite/complicações , Diltiazem/uso terapêutico , Calcinose/diagnóstico por imagem , Calcinose/etiologia , Criança , Feminino , Humanos , Radiografia , Indução de RemissãoRESUMO
OBJECTIVE: Adult onset Still's disease (AOSD) is an inflammatory disorder with elevated serum acute phase proteins. Interleukin-6 is a major contributor to the acute phase response. We therefore examined the serum levels of CRP, SAA and interleukin-6 in active and inactive AOSD. RESULTS: Active patients had significantly elevated CRP, SAA, and interleukin-6 values. After steroid treatment a marked reduction was observed in all three parameters. There was a close kinetics on the fluctuations of CRP and SAA, but not on IL-6. CONCLUSION: Acute phase proteins and IL-6 are useful markers of disease activity in AOSD.
Assuntos
Biomarcadores/sangue , Interleucina-6/sangue , Doença de Still de Início Tardio/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Apolipoproteínas/metabolismo , Proteína C-Reativa/metabolismo , Ensaio de Imunoadsorção Enzimática , Humanos , Pessoa de Meia-Idade , Proteína Amiloide A Sérica/metabolismoRESUMO
Isolated congenital heart block may be associated with Primary Sjögren's Syndrome. In this work we demonstrated that IgG present in the sera of patients with Primary Sjögren's Syndrome (PSS) could bind and activate muscarinic acetylcholine receptors of rat neonatal atria. These antibodies were able to inhibit in a irreversible manner the binding of 3H-QNB to muscarinic cholinergic receptors of purified rat atria membranes. Moreover, IgG from PSS individuals could modify biological effects mediated by muscarinic cholinoceptors activation, i.e. decrease contractility and cAMP and increase phosphoinositide turnover and cGMP. Atropine blocked all of these effects and carbachol mimicked them; confirming muscarinic cholinergic receptors-mediated PSS IgG action. Neither binding nor biological effect were obtained using adult instead of neonatal rat atria. IgG from sera of normal women were not effective in the studied system. The prevalence of cholinergic antibody was 100% in PSS and was independent of Ro/SS-A and La/SS-B antibodies. It could be concluded that antibody against muscarinic cholinergic receptors may be another serum factor to be considered in the pathophysiology of the development of congenital heart block.
Assuntos
Receptores Muscarínicos/imunologia , Síndrome de Sjogren/imunologia , Adulto , Animais , Ligação Competitiva , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Feminino , Humanos , Fosfatidilinositóis/metabolismo , Quinuclidinil Benzilato/metabolismo , RatosRESUMO
In this study we demonstrate that IgG present in the sera of patients with primary Sjögren's syndrome (PSS) could bind and activate muscarinic acetylcholine receptors (mAChRs) of rat parotid gland. These antibodies were able to inhibit in a non-competitive manner the binding of 3H-quinuclidinyl benzilate (QNB) to mAChRs of purified rat parotid gland membranes. Moreover, IgG from PSS could modify biological effects mediated by mAChR activation; i.e. decrease cAMP, increase phosphoinositide turnover without affecting cGMP. Atropine and 4-DAMP blocked all of these effects, and carbachol mimicked them, confirming the M3 subtype mAChRs mediated PSS IgG action. Neither binding nor biological effect were obtained with IgG from sera of normal women. The prevalence of cholinergic antibody was 100% in PSS, and was independent of Ro/SS-A and La/SS-B antibodies. It could be concluded that antibody against mAChRs may be another serum factor to be considered in the pathophysiology of the development of PSS.
Assuntos
Imunoglobulina G/imunologia , Glândula Parótida/imunologia , Fenilcarbamatos , Receptores Muscarínicos/imunologia , Síndrome de Sjogren/imunologia , Adolescente , Agonistas Adrenérgicos beta/farmacologia , Adulto , Animais , Anticorpos Bloqueadores/imunologia , Atropina/farmacologia , Carbacol/farmacologia , Carbamatos/farmacologia , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Feminino , Humanos , Imunoglobulina G/análise , Isoproterenol/farmacologia , Antagonistas Muscarínicos/imunologia , Antagonistas Muscarínicos/farmacologia , Parassimpatolíticos/farmacologia , Fosfatidilinositóis/metabolismo , Piperidinas/farmacologia , Pirenzepina/análogos & derivados , Pirenzepina/farmacologia , Inibidores de Proteases/farmacologia , Quinuclidinil Benzilato/imunologia , Ratos , Ratos Wistar , Síndrome de Sjogren/sangueAssuntos
Bloqueio Cardíaco/congênito , Síndrome de Sjogren/imunologia , Adulto , Autoanticorpos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , PrognósticoRESUMO
OBJECTIVE: To study the association of maternal antibodies to Ro(SSA) and/or La(SSB) with isolated complete congenital heart block (CCHB) in children according to the child's age at detection. METHODS: Sera from 17 mothers of 18 children with CCHB of unidentified cause were studied. Autoantibodies were measured by double immunodiffusion, enzyme linked immunosorbent assay (ELISA), Western blot, and immunoprecipitation from cell extracts. Statistical analysis used the chi 2 test with Yates' correction. RESULTS: CCHB was diagnosed in 12 children of 11 mothers before the age of 3 mo (Group A) and in 6 children of 6 mothers after the age of 17 mo (Group B). Seven Group A mothers and no Group B mother had connective tissue disorders; autoantibodies were found in 9/11 Group A and in 1/6 Group B mothers (p < 0.01). Eight Group A children needed a pacemaker and one other died of cardiac insufficiency, whereas only one of the 6 Group B children needed a pacemaker. Interestingly, this latter child was the only one from Group B whose mother's serum contained autoantibodies. Irrespective of their age at diagnosis, the children with CCHB who needed a pacemaker and the one who died were born to mothers with autoantibodies (p < 0.001). CONCLUSION: CCHB detected before the age of 3 mo is highly associated with the presence of anti-Ro(SSA)/La(SSB) in the mothers, while CCHB diagnosed later is generally not. For epidemiological studies, the former type should be considered early onset as opposed to late onset CCHB in the latter type. Establishing this clinicoserological distinction is also important for the children, since it alerts the clinician to a more severe prognosis (necessity of a pacemaker), even in the rare occurrence of late diagnosed CCHB.
Assuntos
Autoanticorpos/sangue , Autoantígenos/imunologia , Bloqueio Cardíaco/diagnóstico , RNA Citoplasmático Pequeno , Ribonucleoproteínas/imunologia , Adolescente , Western Blotting , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Bloqueio Cardíaco/congênito , Bloqueio Cardíaco/imunologia , Humanos , Imunodifusão , Lactente , Masculino , Testes de Precipitina , Prognóstico , Antígeno SS-BRESUMO
In this work we demonstrated that IgG present in the sera of patients with congenital heart block (CHB) and their mothers could bind and activate beta adrenoceptors and muscarinic cholinergic receptors of neonatal heart. These antibodies were able to inhibit in a noncompetitive manner the binding of [3H]QNB and [3H]CGP to muscarinic cholinergic and beta adrenoceptors of purified neonatal rat myocardial membranes, respectively. Moreover, IgG from children with CHB and their mothers could modify biological effects mediated by these neurotransmitter receptors, i.e., heart contractility and cAMP production. Neither binding nor biological effects were obtained using adult instead of neonatal rat atria. Both reactivities (adrenergic and cholinergic) were independent of Ro/SS-A and La/SS-B antibodies and were absent in the sera of normal women of childbearing age and of normal children. It could be concluded that antibodies against cardiac neurotransmitter receptors may be another serum factor (or factors) to be considered in the pathophysiology of the development of CHB.
Assuntos
Autoanticorpos/sangue , Bloqueio Cardíaco/imunologia , Receptores Adrenérgicos beta/imunologia , Receptores Muscarínicos/imunologia , Adulto , Animais , Feminino , Átrios do Coração/fisiopatologia , Bloqueio Cardíaco/congênito , Humanos , Imunoglobulina G/metabolismo , Técnicas In Vitro , Lactente , Mães , Contração Miocárdica , Miocárdio/metabolismo , RatosRESUMO
To determine whether antibodies against beta adrenergic activity interact with neonatal cardiac cell receptors and alter their physiological behaviour. An "in vitro" experimental model measuring the frequency of contraction, the production of cAMP and binding assay on neonatal and adult rat atria was employed. Sera and IgG fraction from mothers of infants with congenital heart block (CHB) interact with neonatal rat atria increasing the frequency of contraction and cAMP production. These effects were abolished by propranolol, pointing to a beta adrenergic participation. IgG also competed with 3H-CGP to beta adrenergic receptors on neonatal cardiac membranes. Neither the contractile nor the cAMP effects or binding assay were obtained using adult instead of neonatal rat atria. Reactivity against cardiac neurotransmitter receptors may be another serum factor(s) to be considered in the pathophysiology of the development of CHB.
Assuntos
Autoanticorpos/fisiologia , Bloqueio Cardíaco/congênito , Receptores Adrenérgicos beta/imunologia , Animais , Distribuição de Qui-Quadrado , AMP Cíclico/biossíntese , Feminino , Coração/efeitos dos fármacos , Átrios do Coração/fisiopatologia , Bloqueio Cardíaco/imunologia , Humanos , Imunoglobulina G/fisiologia , Técnicas In Vitro , Recém-Nascido , Mães , Contração Miocárdica/efeitos dos fármacos , Propranolol/farmacologia , RatosRESUMO
En este trabajo se empleó un modelo experimental "in vitro" en el cual se midió la frecuencia de las contracciones, la producción de AMPc y la la unión de ligandos específicos al receptor ß adrenérgicos en las aurículas de ratas neonatales y adultas; a fin de, determinar si anticuerpos con actividad ß adrenérgica interactuaban con receptores ß adrenérgicos cardíacos y alteraban su compartimiento fisiológico. Los sueros y la fracción IgG de madres de infantes con bloqueo cardíaco neonatal congénito incrementaron la frecuencia de las contracciones y la producciín de AMPc en el miocardio auricular neonato. Este efecto fue inhibido por propranolol, puntalizando una participación ß adrenérgica. La IgG también compitió con el radiologando específico por los receptores ß adrenérgicos (3H-CGP) en las membranas purificadas de miocardio neonatal. Ni los efectos biológicos ni los ensayos de unión específica fueron modificados cuando se usó miocardio de rata adulta. La reactividad contra adrenoreceptores cardíacos por parte de anticuerpos provenientes de madres de niños con bloqueo neonatal congénito, podría ser otro factor sérico que debería considerarse en la patofisiología del desarrollo del bloqueo neonatal congénito
Assuntos
Humanos , Animais , Feminino , Recém-Nascido , Ratos , Autoanticorpos/fisiologia , Bloqueio Cardíaco/congênito , Receptores Adrenérgicos beta/imunologia , AMP Cíclico/biossíntese , Bloqueio Cardíaco/imunologia , Distribuição de Qui-Quadrado , Cromatografia DEAE-Celulose , Contração Miocárdica , Átrios do Coração/fisiopatologia , Imunoglobulina G/fisiologia , Mães , Propranolol/farmacologiaRESUMO
En este trabajo se empleó un modelo experimental "in vitro" en el cual se midió la frecuencia de las contracciones, la producción de AMPc y la la unión de ligandos específicos al receptor ß adrenérgicos en las aurículas de ratas neonatales y adultas; a fin de, determinar si anticuerpos con actividad ß adrenérgica interactuaban con receptores ß adrenérgicos cardíacos y alteraban su compartimiento fisiológico. Los sueros y la fracción IgG de madres de infantes con bloqueo cardíaco neonatal congénito incrementaron la frecuencia de las contracciones y la producciín de AMPc en el miocardio auricular neonato. Este efecto fue inhibido por propranolol, puntalizando una participación ß adrenérgica. La IgG también compitió con el radiologando específico por los receptores ß adrenérgicos (3H-CGP) en las membranas purificadas de miocardio neonatal. Ni los efectos biológicos ni los ensayos de unión específica fueron modificados cuando se usó miocardio de rata adulta. La reactividad contra adrenoreceptores cardíacos por parte de anticuerpos provenientes de madres de niños con bloqueo neonatal congénito, podría ser otro factor sérico que debería considerarse en la patofisiología del desarrollo del bloqueo neonatal congénito (AU)
Assuntos
Humanos , Animais , Feminino , Estudo Comparativo , Recém-Nascido , Ratos , Receptores Adrenérgicos beta/imunologia , Autoanticorpos/fisiologia , Bloqueio Cardíaco/congênito , Bloqueio Cardíaco/imunologia , AMP Cíclico/biossíntese , Propranolol/farmacologia , Imunoglobulina G/fisiologia , Contração Miocárdica/efeitos dos fármacos , Átrios do Coração/fisiopatologia , Cromatografia DEAE-Celulose , Mães , Distribuição de Qui-QuadradoRESUMO
To determine whether antibodies against beta adrenergic activity interact with neonatal cardiac cell receptors and alter their physiological behaviour. An [quot ]in vitro[quot ] experimental model measuring the frequency of contraction, the production of cAMP and binding assay on neonatal and adult rat atria was employed. Sera and IgG fraction from mothers of infants with congenital heart block (CHB) interact with neonatal rat atria increasing the frequency of contraction and cAMP production. These effects were abolished by propranolol, pointing to a beta adrenergic participation. IgG also competed with 3H-CGP to beta adrenergic receptors on neonatal cardiac membranes. Neither the contractile nor the cAMP effects or binding assay were obtained using adult instead of neonatal rat atria. Reactivity against cardiac neurotransmitter receptors may be another serum factor(s) to be considered in the pathophysiology of the development of CHB.
RESUMO
Las vasculitis sistémicas son un grupo heterogénio de enfermedades caracterizadas por infiltración inflamatoria y necrosis de la pared vascular. Anticuerpos contra citoplasma de polimorfonuclear neutrófilo (ANCA-C y ANCA-P) fueron descriptos como marcadores serológicos de algunas de estas afecciones y de ciertos tipos de glomerulonefritis. La presencia de ANCA se investigó en el suero de 182 pacientes. En 16/17 con Granulomatosis de Wegener (G.W.) (critérios ACR) se encontró ANCA, 14 de ellos con imagen C (en 10 asociada a imagem P) y en los dos restantes, imagem P solamente (p < 0,001, comparando con los otros grupos estudiados). La presencia de estos anticorpos se asoció con la atividad clínica de la enfermedad (p, 0,01). El único paciente ANCA-C positivo fuera de este grupo tenía estonosis subglótica como única manifestación clínica con histología inespecífica, ANCA-P se encontró, además, en 6 por ciento de los casos con Enfermedades del Tejido Conectivo estudiados, y en 6/66 de la Unidad de Diálisis, lo cual sugiere que un mecanismo relacionado al ANCA puede ser el responsable de la nefropatía en aproximadamente el 10//de los pacientes en hemodiálisis crónica. Los resultados obtenidos indican que la investigación de ANCA puede ser un elemento de ayuda útil para el diagnóstico y monitoreo de la actividad clínica en la G.W