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Objective Anti-ribosomal P antibodies (anti-P) are strongly associated with neuropsychiatric lupus. This study was designed to determine whether these antibodies are capable of causing electro-oscillogram (EOSG) and behavior alterations in rats. Methods IgG fraction anti-P positive and affinity-purified anti-P antibodies were injected intraventricularly in rats. Sequential cortical and subcortical EOSGs were analyzed during 30 days. IgG anti-Ro/SS-A and normal IgG were used as controls. Results All 13 animals injected with IgG anti-P demonstrated a high prevalence of polyspikes, diffusely distributed in hippocampal fields and cerebral cortex. These abnormalities persisted approximately a month. Remarkably, an identical electrical disturbance was observed with the inoculation of affinity-purified anti-P antibodies. The EOSG alterations were associated with behavioral disorders with varying degrees of severity in every animal injected with anti-P. In contrast, no changes in EOSG or behavioral disturbances were observed in the control group. Conclusion Our study indicates that anti-P antibodies can directly induce electrophysiological dysfunction in central nervous system particularly in hippocampus and cortex associated with behavior disturbances.
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Encéfalo/fisiopatología , Inmunoglobulina G/administración & dosificación , Ventrículos Laterales/inmunología , Lupus Eritematoso Sistémico/inmunología , Trastornos Mentales/inducido químicamente , Proteínas Ribosómicas/inmunología , Animales , Autoanticuerpos/administración & dosificación , Autoanticuerpos/efectos adversos , Encéfalo/efectos de los fármacos , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/fisiopatología , Modelos Animales de Enfermedad , Femenino , Hipocampo/efectos de los fármacos , Hipocampo/fisiopatología , Humanos , Inmunoglobulina G/efectos adversos , Inyecciones , Lupus Eritematoso Sistémico/fisiopatología , Masculino , Trastornos Mentales/fisiopatología , RatasRESUMEN
OBJECTIVES: To assess ovarian reserve markers and anti-corpus luteum antibodies (anti-CoL) in adult patients with childhood-onset systemic lupus erythematosus (c-SLE). METHOD: Fifty-seven adult c-SLE female patients and 21 healthy controls were evaluated for anti-CoL. Ovarian reserve was assessed by: follicle stimulating hormone (FSH), luteinizing hormone (LH), oestradiol, anti-Müllerian hormone (AMH), and antral follicle count (AFC). Demographic data, menstrual abnormalities, disease activity, damage, and treatment were also analysed. RESULTS: The median current age was similar in adult c-SLE patients and controls (27.7 vs. 27.7 years, p = 0.414). The medians of AMH (1.1 vs. 1.5 ng/mL, p = 0.037) and AFC (6 vs. 16, p < 0.001) were significantly reduced in SLE patients compared to controls without significant menstrual abnormalities. Anti-CoL were solely observed in c-SLE patients (16% vs. 0%, p = 0.103) and were not associated with demographic data, ovarian reserve parameters, disease activity/damage, and treatment. Further evaluation of c-SLE patients treated with cyclophosphamide revealed a higher median of FSH levels compared to c-SLE patients not treated with cyclophosphamide and controls (8.8 vs. 5.7 vs. 5.6 IU/L, p = 0.032) and lower median AMH (0.4 vs. 1.5 vs. 1.5 ng/mL, p = 0.004) and AFC (4.0 vs. 6.5 vs. 16 IU/L, p = 0.001) levels. Nineteen patients treated exclusively with methotrexate demonstrated a negative correlation between the cumulative dose and AMH levels (p = 0.027, r = -0.507). CONCLUSIONS: The present study demonstrated for the first time that a high cumulative methotrexate dose is a possible cause of subclinical ovarian dysfunction in adult c-SLE patients. Further studies are required to confirm this deleterious effect in other rheumatic diseases, particularly juvenile idiopathic arthritis and idiopathic inflammatory myopathy.
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Lupus Eritematoso Sistémico/tratamiento farmacológico , Metotrexato/efectos adversos , Reserva Ovárica/efectos de los fármacos , Adolescente , Adulto , Hormona Antimülleriana/sangre , Cuerpo Lúteo/inmunología , Ciclofosfamida/uso terapéutico , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Lupus Eritematoso Sistémico/inmunologíaRESUMEN
Proteinuria is a major feature of lupus nephritis (LN) and reflects podocyte injury. Analysis of podocyte biomarkers was performed attempting to identify if podocyte phenotype is distinct in pure membranous and proliferative LN. Expression of synaptopodin, Wilms tumor protein 1 (WT1), glomerular epithelial protein 1 (GLEPP1) and nephrin was evaluated in 52 LN biopsies by immunohistochemistry. Preserved synaptopodin expression was observed in only 10 (19.2%) of all biopsies while 42 (80.8%) had reduced expression. Both groups had comparable proteinuria at the time of biopsy (p = 0.22); however, in the mean follow-up of four years there was a tendency toward lower mean levels of proteinuria in patients with preserved synaptopodin staining (0.26±0.23 vs. 0.84±0.90 g/24 h, p = 0.05) compared with those with diminished expression. Thirty-nine (75%) biopsies were classified as proliferative and 13 (25%) as pure membranous. Comparison of podocyte biomarkers demonstrated a predominance of preserved staining of synaptopodin (69.2%), WT1 (69.2%), GLEPP1 (53.9%) and nephrin (60%) in the pure membranous group whereas only <10% of the proliferative showed preserved expression. Our data suggest that in proliferative forms there seems to occur structural podocyte damage, whereas in the pure membranous the predominant preserved pattern suggests a dysfunctional podocyte lesion that may account for the better long-term prognosis of proteinuria outcome.
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Proliferación Celular , Glomerulonefritis Membranoproliferativa/etiología , Glomerulonefritis Membranosa/etiología , Nefritis Lúpica/etiología , Podocitos/patología , Proteinuria/etiología , Adulto , Biomarcadores/análisis , Biopsia , Femenino , Glomerulonefritis Membranoproliferativa/metabolismo , Glomerulonefritis Membranoproliferativa/patología , Glomerulonefritis Membranosa/metabolismo , Glomerulonefritis Membranosa/patología , Humanos , Inmunohistoquímica , Nefritis Lúpica/metabolismo , Nefritis Lúpica/patología , Masculino , Proteínas de la Membrana/análisis , Proteínas de Microfilamentos/análisis , Persona de Mediana Edad , Podocitos/química , Pronóstico , Proteinuria/metabolismo , Proteinuria/patología , Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores/análisis , Factores de Tiempo , Proteínas WT1/análisis , Adulto JovenRESUMEN
OBJECTIVES: To perform systematic assessment of ovarian reserve markers using a combination of tests in juvenile systemic lupus erythematosus (JSLE) patients without amenorrhoea. METHODS: Twenty-seven consecutive JSLE female patients and 13 healthy controls without amenorrhoea were evaluated for 6 months. Ovarian reserve was assessed during early follicular phase by serum levels of follicle stimulating hormone (FSH), luteinising hormone (LH), estradiol, inhibin A, inhibin B and anti-Mullerian hormone (AMH). Ovarian size was measured by abdominal ultrasonography. Demographic data, disease activity, damage and treatment were also analysed. RESULTS: The median of current age was similar in JSLE patients and controls (16.5 vs. 15years, p=0.31) with a significantly higher age at menarche (13 vs. 12years, p=0.03). A trend of lower median total antral follicle count was observed in JSLE compared to controls (9 vs. 14.5, p=0.062) with similar median of other ovarian reserve parameters (p>0.05). Further evaluation of patients treated with cyclophosphamide and those without this treatment revealed a higher median FSH levels (6.4 vs. 4.6 IU/L, p=0.023). Inhibin B, AMH levels and ovarian volume were also lower but did not reach statistical significance (10.8 vs. 27.6 pg/mL, p=0.175; 0.6 vs. 1.5 ng/mL, p=0.276; 3.4 vs. 5 cm3, p=0.133; respectively). LH (2.7 vs. 2.9 IU/L, p=0.43), estradiol (50 vs. 38 pg/mL, p=0.337) and inhibin A (1.1 vs. 0 pg/mL, p=0.489) levels were comparable in both groups. CONCLUSIONS: Our study suggests that ovarian reserve after cyclophosphamide treatment may be hampered in spite of the presence of menstrual cycles emphasising the relevance of gonadal protection during the use of this alkylating agent.
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Ciclofosfamida/efectos adversos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Enfermedades del Ovario/inducido químicamente , Ovario/efectos de los fármacos , Ovario/fisiología , Adolescente , Hormona Antimülleriana/sangre , Antirreumáticos/administración & dosificación , Antirreumáticos/efectos adversos , Niño , Ciclofosfamida/administración & dosificación , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Inhibinas/sangre , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/fisiopatología , Hormona Luteinizante/sangre , Menarquia/efectos de los fármacos , Menarquia/fisiología , Enfermedades del Ovario/sangre , Enfermedades del Ovario/fisiopatología , Adulto JovenRESUMEN
OBJECTIVES: To our knowledge, no study assessed simultaneously a variety of organ-specific autoantibodies and the prevalence of organ-specific autoimmune diseases in juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM). Therefore, the purpose of this study was to evaluate organ-specific autoantibodies and autoimmune diseases in JSLE and JDM patients. METHODS: Forty-one JSLE and 41 JDM patients were investigated for autoantibodies associated with autoimmune hepatitis, primary biliary cirrhosis, type 1 diabetes mellitus (T1DM), autoimmune thyroiditis (AT), autoimmune gastritis and coeliac disease (CD). Patients with positive antibodies were investigated for the respective organ-specific autoimmune diseases. RESULTS: Mean age at diagnosis was higher in JSLE compared to JDM patients (10.3±3.4 vs. 7.3±3.1years, p=0.0001). The frequencies of organ-specific autoantibodies were similar in JSLE and JDM patients (p>0.05). Of note, a high prevalence of T1DM and AT autoantibodies was observed in both groups (20% vs. 15%, p=0.77 and 24% vs. 15%, p=0.41; respectively). Higher frequencies of ANA (93% vs. 59%, p=0.0006), anti-dsDNA (61% vs. 2%, p<0.0001), anti-Ro, anti-Sm, anti-RNP, anti-La and IgG-aCL were observed in JSLE (p<0.05). Organ-specific autoimmune diseases were evidenced only in JSLE patients (24% vs. 0%, p=0.13). Two JSLE patients had T1DM associated with Hashimoto thyroiditis and another had subclinical thyroiditis. Another JSLE patient had CD diagnosis based on iron deficiency anaemia, anti-endomysial antibody, duodenal biopsy compatible to CD and response to a gluten-free diet. CONCLUSIONS: Organ-specific diseases were observed solely in JSLE patients and required specific therapy. The presence of these antibodies recommends the evaluation of organ-specific diseases and a rigorous follow-up.
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Autoanticuerpos/inmunología , Dermatomiositis/inmunología , Lupus Eritematoso Sistémico/inmunología , Adolescente , Enfermedades Autoinmunes/inmunología , Niño , Preescolar , Femenino , Humanos , MasculinoRESUMEN
The antichromatin antibody (aCT) has been described as a useful marker for lupus nephropathy. The relevance of its nephritogenic potential may be appropriately evaluated in the context of renal histopathology. Therefore, the present study investigated the relationship of aCT with a particular histopathologic class of lupus nephritis (LN). Seventy-eight consecutive patients with systemic lupus erythematosus (ACR criteria) and active nephritis who underwent renal biopsy from 1999 to 2004 and with available frozen serum sample obtained at the time of biopsy were selected. aCT was measured by ELISA, and anti-dsDNA was measured by indirect immunofluorescence (IIF) and by ELISA. All renal biopsies were revised in a blinded manner by the same expert renal pathologist. Charts were extensively reviewed for demographic and renal features obtained at the time of biopsy. The prevalence of aCT (>or=20 U) was 59% with a mean titer of 74.3 +/- 38.7 U. Both aCT-positive and aCT-negative groups of patients had similar age, gender distribution, duration of lupus, and duration of renal disease. Anti-dsDNA was detected by IIF in 29.5% and by ELISA in 42.3% of the patients. Concomitant presence of both antibodies was observed in 63% (29/46) [anti-dsDNA by ELISA] and 45.6% (21/46) [anti-dsDNA by IIF] of the patients. Lower serum levels of C3 (73% vs. 40%, P = 0.0058) and C4 (82% vs. 46.7%, P = 0.0021) were more commonly observed in aCT >or= 20 U patients compared to the aCT-negative group. It is important to note that the use of a higher cut-off value (>or=40 U) for aCT test revealed a predominance of class IV LN (58% vs. 33%, P = 0.039) in aCT >or= 40 U compared to aCT < 40 U group. The mean levels of proteinuria, serum albumin, and creatinine were markedly altered but were comparable in both groups (P >or= 0.05). One fourth (26.3%) of the 19 patients with class IV LN and aCT >or= 40 U had no detectable anti-dsDNA (ELISA). These data suggest that high-titer aCT seems to be a valuable biomarker for proliferative class IV of LN.
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Anticuerpos Antinucleares/sangre , Riñón/patología , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/patología , Adulto , Biomarcadores/sangre , Estudios de Cohortes , Femenino , Humanos , Pruebas de Función Renal , Nefritis Lúpica/sangre , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
The aim of the present study was to verify the presence of anti-corpus luteum antibodies (anti-CoL) in systemic lupus erythematosus (SLE) and Hashimoto's thyroiditis (HT) patients, as well as establish its possible correlation with menstrual and/or hormonal disturbances in both populations and with SLE activity. Forty-six patients with SLE, 31 with HT, four with both SLE and HT, and 36 healthy women were studied. Out of these, seven (15.2%) patients with SLE, three (9.7%) with HT, three (75%) with both pathologies, and none of the healthy controls tested positive for anti-CoL. The presence of anti-CoL was not significantly correlated to menstrual disturbance (P = 0.083), changes in the level of follicle stimulating hormone (P = 1.0), luteinizing hormone (P = 0.284), estradiol (P = 0.316), prolactin (P = 1.0) or SLE activity measured by SLEDAI (P = 0.756) in SLE patients. There were not enough patients testing positive for anti-luteal antibodies among those with HT or both HT and SLE (three from each group) for a statistical analysis. In conclusion, we found no association between anti-CoL and menstrual or hormonal disturbance in patients with SLE. Also anti-CoL was not specific for SLE, and was not found to be a marker of ovarian failure in SLE.
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Anticuerpos/sangre , Cuerpo Lúteo/inmunología , Enfermedad de Hashimoto/sangre , Lupus Eritematoso Sistémico/sangre , Trastornos de la Menstruación/sangre , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Enfermedad de Hashimoto/complicaciones , Humanos , Lupus Eritematoso Sistémico/complicaciones , Trastornos de la Menstruación/etiología , Índice de Severidad de la EnfermedadRESUMEN
We have analysed in vitro the complement-fixing activity of anticardiolipin antibodies (C-fix aCL) from patients with persistent and moderate/high titres IgG aCL antibodies: 21 with thrombosis and 11 without thrombosis. Titre and C-fix ability of aCL were measured by ELISA. APS and non-APS patients were similar with regard to mean levels of IgG aCL (46 +/- 24 versus 51 +/- 30 GPL, P = 0.7), frequency of IgM aCL (P = 0.7) and a comparable predominance of IgG2 aCL reactivity on ELISA (95% versus 100%, respectively, P = 1.0). Remarkably, a high frequency of C-fix aCL (71% versus 92%, P = 0.35) was observed in both groups. Similarly, no difference was observed in the mean level of C-fix aCL in APS and non-APS patients (7 +/- 6 versus 9 +/- 8 SDunits, P = 0.3). Analysis of 10 primary and 11 secondary APS also revealed a comparable IgG aCL mean titre (57 +/- 29 versus 37 +/- 11, P = 0.06), frequency of IgM aCL (P = 0.6) and of C-fix aCL (70% versus 73%, P = 0.99). Among APS patients six had exclusive arterial events and seven exclusive venous events. The IgG aCL mean titre (36 +/- 10 versus 36 +/- 11 GPL, P = 0.9) and the frequency of IgM aCL antibodies (P = 0.56) in these subgroups of patients were comparable. There was a trend of higher frequency of C-fix aCL in patients with exclusive venous events (100%) compared to 50% of those with exclusive arterial events (p = 0.07). Importantly, C-fix aCL titre was higher in the former group compared to the later one (8 +/- 5 SDunits versus 2 +/- 2 SDunits, P = 0.016). Our data support the notion of a high frequency of C-fix aCL in APS. Although it does not discriminate those patients without thrombotic events with persistent moderate/high levels of aCL, this property seems to be more relevant in venous events and may provide the basis for further understanding the distinct pathogenic mechanisms underlying arterial and venous occlusive disorders of APS.
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Anticuerpos Anticardiolipina/inmunología , Trombosis/inmunología , Adulto , Anticuerpos Anticardiolipina/análisis , Síndrome Antifosfolípido/inmunología , Pruebas de Fijación del Complemento , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunologíaRESUMEN
The aim of the present study was to analyse in rats the ability of C-ANCA-positive IgG fraction in triggering inflammatory response on pulmonary tissue. Wistar rats (n = 18) were injected via the the internal jugular vein with 20 mg of total C-ANCA-positive IgG fraction isolated from serum of three different Wegener's granulomatosis patients obtained before therapy. Similarly, control rats were treated with IgG fraction from two rheumatoid arthritis patients (n = 7), IgG from six normal human sera (n = 15) or saline (n = 18), respectively. Animals were sacrificed after 24h of injection for histological analysis of the lungs. Vasculitis and inflammatory infiltrate were consistently absent in rats injected with rheumatoid arthritis IgG or saline and in 14/15 of normal IgG treated animals. In contrast, marked vasculitis was observed in all 18 animals injected with C-ANCA-positive IgG fraction. The histological features were characterized by the presence of a perivascular pleomorphic cellular sheath, particularly around small vessels, endothelial adherence and diapedesis of polymorphonuclear leucocytes and presence of granuloma-like lesions. A dose-response relationship was observed between protein concentration of C-ANCA IgG sample and the intensity of the inflammatory response in the animals. In addition, IgG fraction with undetectable C-ANCA, obtained from one patient in remission after treatment, was not able to reproduce the pulmonary tissue alterations induced by its paired IgG that was positive for C-ANCA taken before therapy. The experimental model described herein may be useful to characterize more effectively the pathogenic mechanism of C-ANCA in Wegener's disease.
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Anticuerpos Anticitoplasma de Neutrófilos/toxicidad , Granulomatosis con Poliangitis/inmunología , Inmunoglobulina G/toxicidad , Isoanticuerpos/toxicidad , Enfermedades Pulmonares/etiología , Vasculitis/etiología , Adulto , Animales , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Artritis Reumatoide/sangre , Artritis Reumatoide/inmunología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta Inmunológica , Femenino , Granuloma/etiología , Granuloma/patología , Granulomatosis con Poliangitis/sangre , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Isoanticuerpos/inmunología , Pulmón/irrigación sanguínea , Enfermedades Pulmonares/inmunología , Enfermedades Pulmonares/patología , Ratas , Ratas Wistar , Organismos Libres de Patógenos Específicos , Vasculitis/inmunología , Vasculitis/patologíaRESUMEN
OBJECTIVE: To investigate the presence of autoantibodies directed to corpus luteum (CoL) in systemic lupus erythematosus (SLE) sera and its correlation with menstrual disturbances. METHODS: We evaluated 87 female patients with SLE, < 40 years old, and 23 women with normal menses as controls. Anti-corpus luteum antibody was detected by immunoblot technique. RESULTS: Reactivity to a bovine CoL antigen was found in 22% of SLE sera. Characterization of the target antigen revealed a 67 kDa glycoprotein highly enriched in corpus luteum, but nearly absent in total ovary extract. Similarly, target antigen was also weakly detectable in tissues that produce or metabolize steroids, such as testis, adrenal cortex, and liver, and it was absent in adrenal medulla or HEp-2 cells. Anti-CoL antibody was easily distinguished from other frequent reactivities of SLE sera, including anti-RNP, anti-Sm, anti-Ro/La, anti-dsDNA, or anticardiolipin. The observation of anti-67 kDa reactivity to human CoL suggests a possible pathogenic role in gonadal dysfunction. Indeed, we observed an inverse association of anti-CoL antibody with the duration of hypergonadotropic amenorrhea. Supporting this hypothesis, in patients with normal or irregular menses, the presence of this antibody was associated with elevated serum level of follicle stimulating hormone, an early and specific sign of ovarian lesion. CONCLUSION: Anti-CoL antibody seems to be associated with early stages of ovarian dysfunction in SLE. Moreover, since similar association of antiovarian antibodies has been observed in an experimental model of autoimmune oophoritis, our findings raise the possibility of autoimmune ovarian lesion in patients with SLE.
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Autoanticuerpos/inmunología , Cuerpo Lúteo/inmunología , Lupus Eritematoso Sistémico/inmunología , Trastornos de la Menstruación/inmunología , Adolescente , Adulto , Animales , Biomarcadores , Bovinos , Demografía , Femenino , Humanos , Immunoblotting , Inmunosupresores/inmunología , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/complicaciones , Trastornos de la Menstruación/etiología , Insuficiencia Ovárica Primaria/etiología , Insuficiencia Ovárica Primaria/inmunología , Esteroides/inmunología , Esteroides/uso terapéuticoRESUMEN
The ability of affinity purified anti-52 kDa Ro/SSA antibody from patients without obstetric history of neonatal lupus to cause heart block using an experimental model was investigated. IgG-enriched fractions from sera of 20 systemic lupus erythematosus (SLE) and one Sjögren's syndrome (SS) all positives for anti-Ro/SSA antibodies as detected by CIE, were perfused on isolated whole rabbit hearts. Only six (29%) samples induced A-V block, five of them presenting low anti-Ro/SSA titre. All of them recognized the 52 kDa isoform on ELISA whereas only one had a concomitant binding to the 60 kDa protein. Moreover, affinity purified antibodies from two sera previously known to induce A-V block were obtained by affinity chromatography using a column containing the full-length 52 kDa Ro/SSA fusion protein. Paired eluate and effluent devoid of anti-52 kDa activity from the same patient were individually perfused in whole hearts. The ability to cause cardiac blockade was restricted to the affinity anti-52 kDa eluates. In addition, anti-52 kDa eluates from three IgG fractions that primarily failed to induce blockade remained ineffective. The present study has added to our knowledge that affinity anti-52 kDa Ro/SSA antibodies from mothers with healthy infants are capable of causing in vitro cardiac conduction disturbances. A prospective follow up of these patients will better delineate the clinical usefulness of this experimental model.
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Anticuerpos Antinucleares/efectos adversos , Bloqueo Cardíaco/inducido químicamente , Lupus Eritematoso Sistémico/congénito , Madres , ARN Citoplasmático Pequeño , Anticuerpos Antinucleares/química , Anticuerpos Antinucleares/aislamiento & purificación , Antirreumáticos/efectos adversos , Autoantígenos/inmunología , Contrainmunoelectroforesis , Ensayo de Inmunoadsorción Enzimática , Femenino , Sistema de Conducción Cardíaco/efectos de los fármacos , Humanos , Técnicas In Vitro , Recién Nacido , Lupus Eritematoso Sistémico/inmunología , Pruebas de Precipitina , Ribonucleoproteínas/inmunología , Antígeno SS-BRESUMEN
Sera from 102 patients with chronic Chagas' disease were studied for the presence of autoantibodies to intracellular proteins and nucleic acids by three different methods. Only four sera had autoantibodies detected by indirect immunofluorescence on HEp-2 cells. All of the sera were negative for anti-dsDNA, anti-Ro/SSA, anti-La/SSB, anti-Sm and anti-RNP autoantibodies but 12 (12%) of the sera had low to moderate levels of anti-histone antibodies. When Chagas sera were tested for autoantibodies to a total HeLa cell extract by Western blotting, weak reactivity was observed in 31 sera. Despite significant heterogeneity in the protein Ag targeted by these sera, seven recognized a 23-kDa protein. Strong binding to this 23 kDa protein was observed in one-third of the sera when isolated ribosomes were used as source of Ag. In contrast, no autoreactivity was detected with ribosomal proteins P0, P1, and P2. These findings confirm the presence of autoantibodies in chronic Chagas' disease and indicate a remarkable restricted humoral immune response to human ribosomal proteins. Furthermore, affinity-isolated anti-23-kDa antibody cross-reacted with a Trypanosoma cruzi ribosomal protein of similar molecular weight. This molecular mimicry may be responsible for the apparent breakdown of self-tolerance resulting in tissue damage. Indeed, experiments demonstrating that immunization of mice and rabbit with T. cruzi ribosomes have been reported to induce myocarditis.
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Antígenos de Protozoos/inmunología , Autoanticuerpos/análisis , Enfermedad de Chagas/inmunología , Proteínas Protozoarias/inmunología , Proteínas Ribosómicas/inmunología , Trypanosoma cruzi/inmunología , Animales , Antígenos de Protozoos/análisis , Western Blotting , Reacciones Cruzadas , Humanos , Proteínas Protozoarias/análisis , Proteínas Ribosómicas/análisisRESUMEN
1. We describe new autoantibodies which recognize two cytoplasmic proteins of 30 and 26 kDa. They were detected by Western blot analysis in the sera of 6 of 79 randomly selected systemic lupus erythematosus (SLE) patients and are denoted anti-JA antibodies. This antibody specificity is different from the previously described lupus autoantibodies, anti-P and anti-S10. 2. The targeted autoantigens are trypsin sensitive, and resistant to RNase and DNase treatment. The binding to the antigens was not modified when reticulocyte ribosomes were prepared with protease inhibitors indicating that these are primary antigens and not degradation products. Several lines of evidence suggest that these proteins are almost certainly part of the ribosome. 3. Anti-JA reactivity was not observed in the sera from 60 patients with other autoimmune diseases or from normal individuals. In contrast, 55% of lupus sera selected for a high titer of anti-dsDNA (double stranded DNA) and LE cells were also anti-JA positive. 4. Anti-JA antibodies may be useful as a specific serological marker for disease activity in SLE. The strong association with anti-dsDNA antibodies and LE cell in the sera of SLE patients requires further study.
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Autoanticuerpos/sangre , Autoantígenos/inmunología , Enfermedades Autoinmunes/diagnóstico , Citoplasma/inmunología , Lupus Eritematoso Sistémico/diagnóstico , Ribosomas/inmunología , Especificidad de Anticuerpos , Autoantígenos/sangre , Enfermedades Autoinmunes/epidemiología , Biomarcadores/sangre , Western Blotting , Distribución de Chi-Cuadrado , Técnica del Anticuerpo Fluorescente , Humanos , Lupus Eritematoso Sistémico/epidemiología , Peso Molecular , Estudios RetrospectivosRESUMEN
We describe new autoantibodies which recognize two cytoplasmic proteins of 30 and 26 kDa. They were detected by Western blot analysis in the sera of 6 of 79 randomly selected systemic lupus erithematosus (SLE) patients and are denoted anti-JA antibodies. This antibody specificity is different from the previously described lupus autoantibodies, anti-P and anti-S10. The targeted autoantigens are trypsin sensitive, and resistant to RNase and DNase treatment. The binding to the antigens was not modified when reticulocyte ribosomes were prepared with protease inhibitors indicating that these are primary antigen and not degradation products. Several lines of evidence suggest that these proteins are almost certainly part of the ribosome. Anti-JA reactivity was not observed in the sera from 60 patients with other autoimmune diseases or from normal individulas. In contrast, 55% of lupus sera selected for a high titer of anti-ds DNA (double stranded DNA) and LE cells were also anti-JA positive. Anti-JA antibodies may be useful as a specific serological marker for disease activity in SLE. The strong association with anbti-ds-DNA antibodies and LE cell in the sera of SLE patients requires further study
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Autoanticuerpos , Autoinmunidad , Western Blotting , Lupus Eritematoso SistémicoRESUMEN
Isoniazid (INH) is one among many drugs capable of inducing autoantibodies and, in some cases, a lupus-like syndrome (LE). A longitudinal study was performed in 24 tuberculosis patients treated with INH to detect antibodies (A-AH) to total histones and fractions. Antinuclear antibodies were observed in two patients after treatment. Higher frequency of IgM-AH was also observed. IgM-AH binding to all fractions were observed in those serum samples exhibiting stronger ELISA reactivity. Conversely, binding to only H1 occurred when lower IgM-AH activity was tested. Correlations with clinical expressions of LE were not observed in the present study.
Asunto(s)
Anticuerpos Antinucleares/análisis , Histonas/inmunología , Inmunoglobulina M/análisis , Isoniazida/inmunología , Tuberculosis Pulmonar/inmunología , Adolescente , Adulto , Anciano , Western Blotting , Niño , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Isoniazida/uso terapéutico , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Tuberculosis/inmunología , Tuberculosis Pulmonar/tratamiento farmacológicoRESUMEN
1. An enzyme-linked immunosorbent assay was used to determine the phospholipid specificity of antibodies present in sera from 35 syphilis patients. 2. Based on the cross-reaction obtained against a mixture of cardiolipin, phosphatidylcholine and cholesterol that is standard for flocculation tests according to the Venereal Disease Research Laboratory (CECON, São Paulo, Brazil), all 35 patients tested positive for antibodies of the IgG class whereas 13 (37%) also had IgM antibodies for the same mixture of lipids. IgG antibodies to cardiolipin were demonstrated in 2 patients (6%) and IgM antibodies in 5 (15%). Significant levels of IgG anti-phosphatidylcholine were detected in 3 patients (9%) and IgM antibodies in 4 (11%). IgG anti-phosphatidylethanolamine antibodies were found in 1 patient (3%) and IgM antibodies in 3 (9%). Antibody binding to cardiolipin plus cholesterol or cardiolipin plus phosphatidylcholine was as effective as when the standard mixture of all 3 lipids was used. 3. A comparison with serum from systemic lupus erythematosus patients and inhibition studies using liposomes of cardiolipin or the mixture of 3 lipids suggests that there are at least 3 groups of anticardiolipin antibodies.
Asunto(s)
Anticuerpos Antiidiotipos/análisis , Fosfolípidos/inmunología , Sífilis/inmunología , Especificidad de Anticuerpos , Cardiolipinas/inmunología , Ensayo de Inmunoadsorción Enzimática , Pruebas de Floculación , Humanos , Inmunoglobulina G/análisis , Inmunoglobulina M/análisis , Serodiagnóstico de la SífilisRESUMEN
1. An enzyme-linked immunosorbent assay was used to determine the phospholipid specificity of antibodies in sera from 35 syphilis patients. 2. Based on the cross-reaction obtained aginst a mixture of cardiolipin, phosphatidylcholine and holesterol that is standard for flocculation tests according to the Venereal Disease Research Laboratory (CECON, Säo Paulo, Brazil), all 35 patients tested positive for antibodies of the IgG class whereas 13 (37%) also had IgM antibodies for the same mixture of lipids. IgG antibodies to cardiolipin were demonstrated in 2 patients (6%) and IgM antibodies in 5 (15%). Significant levels of IgG anti-phosphatidylcholine were detected in 3 patients (9%) and IgM antibodies in 4(11%). IgG anti-phosphatidylethanolamine antibodies were found in 1 patient (3%) and IgM antibodies in 3(9%). Antibody binding to cardiolipin plus cholesterol or cardiolipin plus phosphatidycholine was as effective as when the standard mixture of all 3 lipids was used. 3. A comparison with serum from systemic lupus erythematosus patients and inhibition studies using liposomes o cardiolipin or the mixture of 3 lipids suggests that there are at least 3 groups of anticardiolipin antibodies
Asunto(s)
Humanos , Anticuerpos Antiidiotipos/análisis , Ensayo de Inmunoadsorción Enzimática , Pruebas de Floculación , Fosfolípidos/inmunología , Sífilis/inmunología , Especificidad de Anticuerpos , Cardiolipinas/inmunología , Inmunoglobulina G/análisis , Inmunoglobulina M/análisisRESUMEN
Recent studies have shown that anti-DNA and anticardiolipin antibodies in patients with SLE may cross-react. Using an ELISA for determination of these antibodies, a strong association between IgG anti-denatured DNA and IgG anticardiolipin antibodies was found. Eight sera samples with the highest levels of both antibodies were selected to determine the possibility of a cross-reaction. The levels of anticardiolipin were not affected by denatured DNA in concentrations adequate to inhibit the anti-DNA binding. These data did not confirm previous studies using monoclonal antibodies showing cross reactivity between the two groups of antibodies. Nevertheless, a population of antibodies that may cross-reacts, in some special cases, cannot be ruled out.