Subject(s)
Heart Block/congenital , Sjogren's Syndrome/immunology , Adult , Autoantibodies , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , PrognosisSubject(s)
Antibodies, Antinuclear/immunology , Lupus Erythematosus, Systemic/immunology , Adult , Aged , Female , Humans , Male , Middle Aged , Remission, SpontaneousABSTRACT
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.
Subject(s)
Autoantibodies/blood , Autoantigens/immunology , Heart Block/diagnosis , RNA, Small Cytoplasmic , Ribonucleoproteins/immunology , Adolescent , Blotting, Western , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Female , Heart Block/congenital , Heart Block/immunology , Humans , Immunodiffusion , Infant , Male , Precipitin Tests , Prognosis , SS-B AntigenABSTRACT
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
Subject(s)
Humans , Autoantibodies/analysis , Granulomatosis with Polyangiitis/diagnosis , Diagnosis, Differential , Connective Tissue Diseases/diagnosis , Connective Tissue Diseases/blood , Granulomatosis with Polyangiitis/blood , Renal DialysisABSTRACT
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 (AU)
Subject(s)
Humans , Granulomatosis with Polyangiitis/diagnosis , Autoantibodies/analysis , Granulomatosis with Polyangiitis/blood , Connective Tissue Diseases/diagnosis , Connective Tissue Diseases/blood , Renal Dialysis , Diagnosis, DifferentialABSTRACT
Systemic vasculitis are an heterogeneous group of diseases characterized by inflammatory infiltration and necrosis of blood vessel walls. Antineutrophil cytoplasmic antibodies (ANCA) with different immunofluorescent patterns (C or P) have been described as serological markers of some of these diseases and some types of glomerulonephritis. The presence of ANCA by immunofluorescence on normal fixed polymorphonuclear neutrophils was investigated in 182 patients. Results are depicted in Table 1. ANCA was present in 16/17 (94%) patients with Wegener Granulomatosis (W.G.) (ACR criteria) (p < 0.001). In 14 out of the 16 (82%), the pattern was ANCA-C (associated in 10 with ANCA-P) and only ANCA-P was observed in the remaining two. The presence of ANCA was associated with active disease: 15/16 samples of active patients and 3/9 of inactive patients were ANCA positive (p < 0.01). Among the other groups, ANCA-C was detected in only one patient with isolated subglottal stenosis. The specificity of ANCA-C for W.G. was 99%. ANCA-P was also detected in 3/49 (6%) patients with connective tissue disorders and in 3/63 (5%) patients in chronic hemodialysis with exclusive or predominant renal disease of unknown etiology. Three additional ANCA positive patients with known diagnosis (2 W.G. and 1 Systemic Lupus Erythematosus) were also in hemodialysis in the same unit. Thus, an ANCA related mechanism may be involved in the pathogenesis of approximately 10% of cases undergoing this procedure. None of 45 sera submitted for the detection of antinuclear antibodies were ANCA positive. Detection of ANCA (especially C pattern) may be of help in the diagnosis of W.G. and in monitoring clinical activity of the disease.
Subject(s)
Autoantibodies/analysis , Autoimmune Diseases/immunology , Granulomatosis with Polyangiitis/immunology , Antibodies, Antineutrophil Cytoplasmic , Autoimmune Diseases/blood , Biomarkers/analysis , Connective Tissue Diseases/blood , Connective Tissue Diseases/immunology , Granulomatosis with Polyangiitis/blood , Humans , Renal DialysisABSTRACT
Systemic vasculitis are an heterogeneous group of diseases characterized by inflammatory infiltration and necrosis of blood vessel walls. Antineutrophil cytoplasmic antibodies (ANCA) with different immunofluorescent patterns (C or P) have been described as serological markers of some of these diseases and some types of glomerulonephritis. The presence of ANCA by immunofluorescence on normal fixed polymorphonuclear neutrophils was investigated in 182 patients. Results are depicted in Table 1. ANCA was present in 16/17 (94
) patients with Wegener Granulomatosis (W.G.) (ACR criteria) (p < 0.001). In 14 out of the 16 (82
), the pattern was ANCA-C (associated in 10 with ANCA-P) and only ANCA-P was observed in the remaining two. The presence of ANCA was associated with active disease: 15/16 samples of active patients and 3/9 of inactive patients were ANCA positive (p < 0.01). Among the other groups, ANCA-C was detected in only one patient with isolated subglottal stenosis. The specificity of ANCA-C for W.G. was 99
. ANCA-P was also detected in 3/49 (6
) patients with connective tissue disorders and in 3/63 (5
) patients in chronic hemodialysis with exclusive or predominant renal disease of unknown etiology. Three additional ANCA positive patients with known diagnosis (2 W.G. and 1 Systemic Lupus Erythematosus) were also in hemodialysis in the same unit. Thus, an ANCA related mechanism may be involved in the pathogenesis of approximately 10
of cases undergoing this procedure. None of 45 sera submitted for the detection of antinuclear antibodies were ANCA positive. Detection of ANCA (especially C pattern) may be of help in the diagnosis of W.G. and in monitoring clinical activity of the disease.
Subject(s)
Autoantibodies , Blood Coagulation Disorders/immunology , Blood Coagulation Factors/immunology , Fetal Death/etiology , Lupus Erythematosus, Systemic/immunology , Pregnancy Complications/immunology , Female , Humans , Lupus Coagulation Inhibitor , Pregnancy , Pregnancy Complications, Hematologic/immunologyABSTRACT
Sera from 30 chronic chagasic patients together with 52 control samples (34 with other pathological conditions and 18 from normal individuals) were titrated by the indirect immunofluorescent technique (IFA) on Trypanosoma cruzi amastigotes. Acetone-fixed cryostat sections of skeletal muscle of Rockland mice 10 days post-infection with the RA isolate of T. cruzi were used as substrate. Results were compared with titres obtained by conventional IFA on epimastigotes. All 52 control sera had amastigote titres less than or equal to 2 double dilutions (dd) as compared with epimastigote values. Out of the 30 chagasic samples, differences were greater than or equal to 4 dd (less than or equal to 1 log) for 22, 3 dd for 5 and less than or equal to 2 dd for the remaining 3, when comparing amastigote and epimastigote titres. These results show that the use of amastigotes in cryostat sections of infected tissue for performing Chagas' serology in a simple, adequate and sensitive method.
Subject(s)
Chagas Disease/diagnosis , Trypanosoma cruzi/immunology , Antibodies/analysis , Fluorescent Antibody Technique , Humans , Muscles/immunologyABSTRACT
Hacen aproximadamente 12 años se demostró en el suero de individuos chagásicos la presencia de un anticuerpo que, por inmunofluorescencia indirecta, reacciona con endocardio, vasos sanguíneos e intersticio de músculo cardíaco (anticuerpo EVI). En los primeros trabajos, se expresó erróneamente que dicha reactividad tenía carácter de autoanticuerpo; más recientemente se determinó su naturaleza heterófila. El propósito del presente trabajo fue determinar qué sistema está involucrado en la respuesta autoinmune humoral contra tejido cardíaco en la enfermedad de Chagas, su prevalencia y especificidad. La presencia de anticuerpos que reaccionan con cortes por criostato de corazón humano grupo 0 fue investigada por la técnica de inmunofluorescencia indirecta en pacientes chagásicos y controles. Los resultados positivos fueron hallados con la siguiente prevalencia: cardiopatía chagásica crónica: 22/34 (64%); infectados asintomáticos: 16/42 (38%); infectados sin datos clínicos: 19/43 (44%); cardiopatías congénitas (pre-cirugía); 0/17 y post-cirugía: 3/5; valvulopatía reumática y cardiopatía isquémica: 7/24 (34%); lupus eritematoso sistémico: 6/15 (40%); artritis reumatoidea: 5/17 (29%); osteoartritis (pacientes en la 6ª y 7ª década de vida): 4/19 (21%); controles normales (ciudad de Buenos Aires): 2/29 (7%); controles normales (provincia de Jujuy): 3/16 (19%). La imagen observada fue intracelular siguiendo las estrías. Los experimentos de absorción con glóbulos rojos de cobayo y con proteínas purificadas de músculo demostraron que la reacción intracelular es independiente del anticuerpo EVI, y es removida con miosina. En un caso, la autorreactividad fue confirmada entre una biopsia de miocardio y el suero del mismo paciente. Los títulos de reactividad de los anticuerpos oscilaron entre 1:15 y 1:60. La IgG estuvo siempre involucrada y en algunos casos también la IgM. El anticuerpo no fija C3. El presente estudio demuestra la existencia de una verdadera reacción autoinmune con miocardio en la enfermedad de Chagas. Su significado debe ser aún demostrado, pero podría ser secundario al daño tisular
Subject(s)
Humans , Histocompatibility Antigens Class II/immunology , Chagas Cardiomyopathy/immunology , Fluorescent Antibody TechniqueABSTRACT
Hacen aproximadamente 12 años se demostró en el suero de individuos chagásicos la presencia de un anticuerpo que, por inmunofluorescencia indirecta, reacciona con endocardio, vasos sanguíneos e intersticio de músculo cardíaco (anticuerpo EVI). En los primeros trabajos, se expresó erróneamente que dicha reactividad tenía carácter de autoanticuerpo; más recientemente se determinó su naturaleza heterófila. El propósito del presente trabajo fue determinar qué sistema está involucrado en la respuesta autoinmune humoral contra tejido cardíaco en la enfermedad de Chagas, su prevalencia y especificidad. La presencia de anticuerpos que reaccionan con cortes por criostato de corazón humano grupo 0 fue investigada por la técnica de inmunofluorescencia indirecta en pacientes chagásicos y controles. Los resultados positivos fueron hallados con la siguiente prevalencia: cardiopatía chagásica crónica: 22/34 (64%); infectados asintomáticos: 16/42 (38%); infectados sin datos clínicos: 19/43 (44%); cardiopatías congénitas (pre-cirugía); 0/17 y post-cirugía: 3/5; valvulopatía reumática y cardiopatía isquémica: 7/24 (34%); lupus eritematoso sistémico: 6/15 (40%); artritis reumatoidea: 5/17 (29%); osteoartritis (pacientes en la 6¬ y 7¬ década de vida): 4/19 (21%); controles normales (ciudad de Buenos Aires): 2/29 (7%); controles normales (provincia de Jujuy): 3/16 (19%). La imagen observada fue intracelular siguiendo las estrías. Los experimentos de absorción con glóbulos rojos de cobayo y con proteínas purificadas de músculo demostraron que la reacción intracelular es independiente del anticuerpo EVI, y es removida con miosina. En un caso, la autorreactividad fue confirmada entre una biopsia de miocardio y el suero del mismo paciente. Los títulos de reactividad de los anticuerpos oscilaron entre 1:15 y 1:60. La IgG estuvo siempre involucrada y en algunos casos también la IgM. El anticuerpo no fija C3. El presente estudio demuestra la existencia de una verdadera reacción autoinmune con miocardio en la enfermedad de Chagas. Su significado debe ser aún demostrado, pero podría ser secundario al daño tisular (AU)
Subject(s)
Humans , Histocompatibility Antigens Class II/immunology , Chagas Cardiomyopathy/immunology , Fluorescent Antibody TechniqueABSTRACT
A patient with fatal acute pulmonary vasculitis complicating systemic lupus erythematosus (SLE) of ten years duration is described. The patient died seven days after an uneventful pregnancy and delivery. Pathologic examination demonstrated acute necrotizing changes as well as organized lesions in pulmonary arteries. Acute pulmonary arteritis is rare in SLE and may develop as one of the major complications of the disease in the potentially dangerous post-partum period.
Subject(s)
Arteritis/pathology , Lupus Erythematosus, Systemic/pathology , Puerperal Disorders/pathology , Pulmonary Artery/pathology , Adult , Arteritis/etiology , Female , Humans , Lupus Erythematosus, Systemic/complications , PregnancyABSTRACT
The Swiss mouse is considered a satisfactory model for experimental chronic chagasic myocarditis and there is some evidence of an immunopathologic mechanism in the development of this disease. To further support this conjecture, 45-day-old albino Swiss mice (40 animals) were immunized with homologous heart in complete Freund's adjuvant. As controls, 20 animals were likewise inoculated with allogeneic testis, as "non-related" antigen. Three mice from the former group died suddenly at 19-21 days postinoculation while the survivors were sacrificed at 60 days for serum samples, and histologic analysis of the heart and skeletal muscle. Electrocardiographic records were taken at Days 0, 30, and 60 postinoculation. Of myocardium-inoculated animals and testis-inoculated mice 33/37 (89%) and 1/20 (5%), respectively, exhibited myocarditis (P less than 0.001). Histologic lesions were highly reminiscent of those observed in chronic experimental Chagas' disease of Swiss mice. Antimuscle antibodies were seen, by indirect immunofluorescence employing cryostat sections, in 30/33 (91%) of the former group and in 3/20 (15%) of the latter (P less than 0.001), some of which recognized a surface antigen of primary cultured fetal rat myocardiocytes. Mice inoculated with myocardium also exhibited electrocardiographic abnormalities consisting in QRS interval widening. Results show that following an autoimmune experimental design the main features of chronic chagasic myocarditis may be reproduced in the Swiss mouse. This agrees with the likely role of an immunopathologic mechanism in heart damage due to Trypanosoma cruzi infection.
