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OBJECTIVE: To evaluate the performance of the Systemic Lupus Erythematosus Risk Probability Index (SLERPI) in Colombian patients with systemic lupus erythematosus (SLE). METHODS: The Colombian cohort included 435 SLE patients and 430 controls with other autoimmune diseases (ADs). Clinical and serological data were collected, and SLE was indicated by SLERPI scores > 7. The American College of Rheumatology (ACR)-1997, Systemic Lupus International Collaborating Clinics (SLICC)-2012, and European League Against Rheumatism (EULAR)/ACR-2019 criteria were used as reference standards. The impact of overt polyautoimmunity (PolyA) on SLERPI performance was assessed. Additionally, multivariate lineal regression analysis was performed to evaluate the contribution of SLERPI features to the overall SLERPI score. RESULTS: SLE patients had higher SLERPI scores (P < 0.0001), with almost 90% meeting "definite" lupus criteria. Main factors influencing SLERPI included immunological disorder (ß:44.75, P < 0.0001), malar/maculopapular rash (ß:18.43, P < 0.0001), and anti-nuclear antibody positivity (ß:15.65, P < 0.0001). In contrast, subacute cutaneous lupus erythematosus/discoid lupus erythematosus (ß:2.40, P > 0.05) and interstitial lung disease (ß:-21.58, P > 0.05) were not significant factors to the overall SLERPI score. SLERPI demonstrated high sensitivity for SLE, both for the overall SLE group and for those without overt PolyA (95.4% and 94.6%, respectively), but had relatively low specificity (92.8% and 93.7%, respectively). The model showed high sensitivity for hematological lupus (98.8%) and lupus nephritis (96.0%), but low sensitivity for neuropsychiatric lupus (93.2%). Compared to the ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria, SLERPI yielded the highest sensitivity and lowest specificity. CONCLUSION: SLERPI efficiently identified SLE patients in a Colombian cohort, showing high sensitivity but low specificity. The model effectively distinguishes SLE patients, even in the presence of concurrent overt PolyA. Key Points â¢SLERPI has a high sensitivity, but low specificity compared to ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria in the Colombian population. â¢Within the SLERPI score, immunological disorder, malar/maculopapular rash, and anti-nuclear antibody positivity are the strongest predictors of SLE. â¢SLERPI model can efficiently distinguish patients with SLE, regardless of concomitant overt PolyA. â¢SLERPI demonstrates high sensitivity in identifying hematological and nephritic subphenotypes of SLE.
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Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Femenino , Colombia/epidemiología , Adulto , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Estudios de Cohortes , Anticuerpos Antinucleares/sangre , Medición de Riesgo , Probabilidad , Estudios de Casos y Controles , Factores de Riesgo , Adulto JovenRESUMEN
Systemic Lupus Erythematosus (SLE) is an autoimmune disorder that causes a breakdown of immune tolerance. Current treatments mainly involve general immunosuppression, increasing the risk of infections. On the other hand, Bacillus Calmette-Guérin (BCG) has been investigated as a potential therapy for autoimmune diseases in recent years, prompting an ongoing investigation. This study aimed to evaluate the effect of BCG vaccination on early and late clinical presentation of SLE in a murine disease model. MRL/MPJ-Faslpr mice were immunized with BCG or treated with PBS as a control. The progress of the disease was evaluated at 27 days post-immunization (dpi) (early) and 56 dpi (late). Clinical parameters and proteinuria were monitored. Blood samples were collected for measurement of antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), and cytokine determination was performed using ELISA. Samples collected from mice were analyzed by flow cytometry and histopathology. We observed a clinical improvement in BCG-treated mice, reduced proteinuria in the latter stages of the disease, and decreased TNF-α. However, BCG did not elicit significant changes in ANAs, anti-dsDNA, histopathological scores, or immune cell infiltration. BCG was only partially beneficial in an SLE mouse model, and further research is needed to determine whether the immunity induced by this vaccine can counteract lupus's autoimmune response.
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Anticuerpos Antinucleares , Vacuna BCG , Modelos Animales de Enfermedad , Lupus Eritematoso Sistémico , Animales , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/tratamiento farmacológico , Ratones , Anticuerpos Antinucleares/sangre , Anticuerpos Antinucleares/inmunología , Vacuna BCG/inmunología , Femenino , Citocinas/metabolismo , Proteinuria/inmunología , Proteinuria/etiología , Vacunación , Ratones Endogámicos MRL lpr , Mycobacterium bovis/inmunología , Factor de Necrosis Tumoral alfa/sangreRESUMEN
BACKGROUND: In general, patients are referred for rheumatological evaluation due to isolated laboratory abnormalities, especially antinuclear antibody (ANA) positivity, with the risk of more severe patients remaining on the waiting list for longer than desired. The aim of this study was to analyze the demographic, clinical, and laboratory information of patients referred to a specialized rheumatological care unit because of positive antinuclear antibody. METHODS: This is a retrospective study of 99 out of 1670 patients seen by the same rheumatologist between 01/01/2011 and 01/01/2019. Patients whose referrals were exclusively due to the ANA test result and the specialist's final diagnosis being "abnormal finding of serum immunological test" (ICD-10 R769) were included. Sociodemographic, clinical, and laboratory information were extracted from the consulting rheumatologist's chart. Descriptive statistics were used for data analysis. RESULTS: A total of 99 patients were included, most of whom were female (84.8%) with a median age of 49 years. At the moment of specialist's appointment, 97 patients (97.9%) repeated the ANA test, and 77 patients remained positive. Of these, only 35 (35.35%) were in a high titer range (greater than or equal to 1:320). Complete blood count for cytopenia's investigation was not performed in a high percentage of patients (22.2%), as well as urinalysis (31.3%). In addition, more than 70% of patients score 0 to 1 classification criteria for Systemic Lupus Erythematosus, according to SLE - ACR 1987 (American College of Rheumatology) and SLICC 2012 (Systemic Lupus International Collaborating Clinics). CONCLUSIONS: Most patients are still referred for specialized evaluation due to the misinterpretation of laboratory tests that were inappropriately requested in patients without clinical evidence of autoimmune rheumatic disease.
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Anticuerpos Antinucleares , Derivación y Consulta , Humanos , Anticuerpos Antinucleares/sangre , Femenino , Masculino , Persona de Mediana Edad , Estudios Transversales , Brasil , Estudios Retrospectivos , Adulto , Enfermedades Reumáticas/diagnóstico , Reumatología , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/inmunología , AncianoRESUMEN
TREX1 acts in the initial prevention of an autoimmune response, but it may contribute to the permissiveness of retrovirus infections. This study investigated the association between the levels of TREX1 gene expression with the polymorphisms TREX1 rs3135941 (T/C) and TREX1 rs3135945 (G/A), and the presence of antinuclear antibodies (ANA) in antiretroviral therapy (ART)-naïve individuals and after 1 year of treatment. Blood samples from 119 individuals with HIV-1 were subjected to genotyping of polymorphisms and quantification of TREX1 gene expression and HIV-1 viral load by qPCR. The concentration of IFN-α and the number of CD4+/CD8+ T lymphocytes were determined by ELISA and flow cytometry, respectively; ANA was investigated by immunofluorescence. A control group of 167 seronegative individuals was used for the comparison of genotypic frequencies. The frequency of the polymorphisms were not associated with HIV infection or with variations in the expression of TREX1 and IFN-α (p > 0.05). ART-naïve individuals exhibited higher TREX1 expression and lower IFN-α expression. After 1 year of ART, TREX1 levels were reduced, while IFN-α and CD4+ T lymphocytes were elevated (p < 0.05). Some individuals on ART presented ANA. These results suggest that ART-mediated restoration of immune competence is associated with a reduction in TREX1 expression, which may induce the development of ANA, regardless of the polymorphism investigated.
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Exodesoxirribonucleasas , Infecciones por VIH , VIH-1 , Reconstitución Inmune , Fosfoproteínas , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Antinucleares/sangre , Linfocitos T CD4-Positivos/inmunología , Exodesoxirribonucleasas/genética , Exodesoxirribonucleasas/metabolismo , Genotipo , Infecciones por VIH/inmunología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Infecciones por VIH/virología , VIH-1/inmunología , Reconstitución Inmune/genética , Reconstitución Inmune/inmunología , Interferón-alfa/sangre , Interferón-alfa/metabolismo , Fosfoproteínas/genética , Polimorfismo de Nucleótido Simple , Carga Viral , Antirretrovirales/efectos adversos , Antirretrovirales/uso terapéuticoRESUMEN
Introduction: The indirect immunofluorescence assay on HEp-2 cells (HEp-2/IFA) is used worldwide for screening for autoantibodies to cellular antigens. Cell culture and fixation methods influence the cell distribution of autoantigens and the preservation of epitopes. Therefore, discrepancy of results obtained using different HEp-2/IFA kits (interkit nonreproducibility) is a common phenomenon in the clinical laboratory routine. Objective: This study evaluated the interkit nonreproducibility of HEp-2/IFA results using samples from patients with systemic autoimmune disease (SAD), nonautoimmune diseases (NAD), and healthy blood donors (HBD). Methods: Serum from 275 SAD patients, 293 NAD patients, and 300 HBD were processed at 1:80 dilution using four HEp-2 kits according to the manufacturers' instructions. Interkit reproducibility was determined for positive/negative results and patterns. The agreement of positive/negative results among kits for each sample was determined as the reactivity agreement score (RAS). The pattern reproducibility score (PRS) in each sample was calculated as a function of the number of kits showing equivalent patterns. Qualitative variables and ordinal variables were analyzed by the Chi-square and Mann-Whitney U tests, respectively. Results: A total of 402 samples were nonreactive in all kits and were considered devoid of autoantibodies. Further analysis included the 466 reactive samples (238 SAD, 119 NAD, 109 HBD). Reactivity to the nucleus had the highest interkit reproducibility (RAS = 83.6), followed by the metaphase plate (RAS = 78.9), cytoplasm (RAS = 77.4), and nucleolus (RAS = 72.4). Interkit reproducibility was higher in SAD (RAS = 78.0) than in NAD (RAS = 70.6) and HBD (RAS = 71.3) groups. Samples with strong reactivity (++++/4 and +++/4) had higher interkit reproducibility than those with weak reactivity (+/4). In the SAD group, RAS for nuclear reactivity was 87.5% for strongly reactive samples as opposed to 4.4% for weakly reactive samples, and the same was observed for NAD and HBD samples. The most robust patterns were the centromere AC-3 (PRS = 78.4), multiple nuclear dots AC-6 (PRS = 73.6), nuclear coarse speckled AC-5 (PRS = 71.3), nuclear homogeneous AC-1 (PRS = 67.9), and the reticular cytoplasmic AC-21 (PRS = 68.6). Conclusion: Interkit nonreproducibility in HEp-2/IFA is prevalent and occurs with the highest frequency with weakly reactive samples. International initiatives with the engagement of in vitro diagnostic industry are encouraged to promote the harmonization of the properties and performance of HEp-2/IFA commercial kits.
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Anticuerpos Antinucleares/inmunología , Autoanticuerpos/inmunología , Enfermedades Autoinmunes/inmunología , Técnica del Anticuerpo Fluorescente Indirecta/métodos , Juego de Reactivos para Diagnóstico/normas , Anticuerpos Antinucleares/sangre , Autoanticuerpos/sangre , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/diagnóstico , Línea Celular Tumoral , Humanos , Juego de Reactivos para Diagnóstico/clasificación , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
OBJECTIVES: We aim to describe a rare case of a young patient with a catastrophic antiphospholipid syndrome (cAPS) who evolved to systemic lupus erythematosus (SLE).Methodology: Case report description. CASE REPORT: A 15 years old girl came to the emergency department with acute peritonitis secondary to ischemic perforation of the sigmoid. Angiotomography was suggestive of a thrombotic occlusion of the upper mesenteric artery. Laboratory tests revealed a positive lupus anticoagulant and antinuclear antibodies. A cAPS diagnosis was determined based on more than three different sites of thrombosis (lung, kidney, spleen and sigmoid) in less than one week with a lupus anticoagulant. She was treated with intravenous methylprednisolone 1 mg/kg/day associated with intravenous heparin followed by intravenous immunoglobulin. She had a very good outcome with a total improvement and was discharged from the hospital after 2 months. After 12 weeks, the lupus anticoagulant remained positive. After two months, a systemic lupus erythematosus was diagnosed. She was treated with increasing dose of prednisone and azathioprine 100 mg/day and hydroxychloroquine were added to the treatment. After 2 weeks, she was asymptomatic. She is currently well, asymptomatic using hydroxychloroquine, azathioprine and warfarin. CONCLUSION: This article reports a very unusual presentation which is rarely reported and clinicians should be alert to the possibility that CAPS may be the presenting event for SLE patients, condition known in adults and should also be remembered in pediatric scenario.
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Síndrome Antifosfolípido/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Peritonitis/complicaciones , Trombosis/etiología , Adolescente , Anticuerpos Antinucleares/sangre , Síndrome Antifosfolípido/diagnóstico , Enfermedad Catastrófica , Femenino , Heparina/uso terapéutico , Humanos , Hidroxicloroquina/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéutico , Inhibidor de Coagulación del Lupus/sangre , Lupus Eritematoso Sistémico/diagnóstico , Metilprednisolona/uso terapéutico , Resultado del TratamientoRESUMEN
Background The objective of the study was to determine whether the staining pattern and titer of indirect immunofluorescence assay on HEp-2 cells (HEp-2 IFA) are associated with systemic lupus erythematosus (SLE) disease activity. Methods A total of 269 consecutive patients meeting the ACR and SLICC criteria for SLE were classified into three groups according to the SLE Disease Activity Index 2000 (SLEDAI2K): Remission (SLEDAI2K = 0; n = 47); Intermediate (SLEDAI2K = 1-5; n = 111); Active (SLEDAI2K ≥ 6; n = 111). All subjects were assessed for HEp-2 IFA titer and staining pattern and nine traditional parameters of SLE disease activity. After a 6 to 12-month interval, 101 of the 269 patients were reassessed. Results HEp-2 IFA homogeneous nuclear pattern (AC-1) occurred more frequently in the Active Group compared to the Remission Group (p < 0.001). Fine speckled nuclear pattern (AC-4) tended to occur more frequently in the Remission Group compared to the Active Group (p = 0.054). Subjects with AC-1 pattern had higher SLEDAI (8.8 ± 7.6) than those with AC-4 (4.8 ± 5.2) (p < 0.001). HEp-2 IFA titer and anti-nuclear antibody by enzyme-linked immunosorbent assay (ANA-ELISA) values were lower in the Remission Group compared to the other two groups (p < 0.001). Multivariate analyses identified only ELISA anti-dsDNA as an independent variable associated with disease activity. In follow-up analysis, HEp-2 IFA titer decreased significantly in the 33 subjects with decreased disease activity (p = 0.002). Receiver operator characteristic (ROC) curve analysis for determination of disease activity showed equivalent areas under the curve (AUC) for HEp-2 IFA titer and traditional disease activity parameters. Conclusions HEp-2 IFA pattern and titer can reflect SLE disease activity and may be considered in conjunction with other laboratory and clinical parameters in the assessment of SLE disease activity.
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Anticuerpos Antinucleares/sangre , Ensayo de Inmunoadsorción Enzimática/métodos , Lupus Eritematoso Sistémico/inmunología , Adulto , Línea Celular , ADN/inmunología , Femenino , Humanos , Lupus Eritematoso Sistémico/sangre , Masculino , Persona de Mediana Edad , Nucleosomas/inmunología , Estudios ProspectivosRESUMEN
Anti-rods and rings (anti-RR) antibody induction is related to the combination of interferon and ribavirin in the treatment of hepatitis C virus (HCV) infection. If the main factor leading to this autoimmune reaction is the combination of these drugs, is not well known, but in vitro studies shows that ribavirin alone can induce rods and rings structures. New direct-acting antivirals (DAAs) permit HCV treatment without needing interferon but may be associated with ribavirin in the most difficult-to-treat patients. The aim of this study is to evaluate the occurrence of anti-RR in patients with chronic HCV infection, before and after 12 weeks of treatment with DAAs, with and without ribavirin. From Jun 2016 to Oct 2017, 52 HCV-infected patients were screened for anti-RR before and after DAA therapy, including sofosbuvir, daclatasvir, simeprevir, and ribavirin. Serum samples were analyzed using indirect immunofluorescence. The anti-RR was present in 11 (21%) of the 52 patients (51.9% male and mean age of 59.1 years) before using DAAs. All of them had been previously treated and previous exposed to interferon/ribavirin, with exposure time to ribavirin associated with the presence of anti-RR. After 12 weeks of DAA treatment, 3 patients (5.7%) developed the antibody in low titers, and two of them (66%) were interferon/ribavirin experienced. Only one of the 29 naïve patients (3.44%) developed anti-RR during the current treatment. Anti-RR was present in patients previously treated with interferon/ribavirin and can emerge after DAA treatment probably at a lower frequency than after interferon/ribavirin treatment.
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Anticuerpos Antinucleares/sangre , Antivirales/administración & dosificación , Hepacivirus/inmunología , Hepatitis C Crónica/inmunología , Anciano , Anticuerpos Antinucleares/inmunología , Carbamatos/administración & dosificación , Quimioterapia Combinada/métodos , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Hepatitis C Crónica/sangre , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Humanos , Imidazoles/administración & dosificación , Interferón-alfa/administración & dosificación , Masculino , Persona de Mediana Edad , Pirrolidinas/administración & dosificación , Ribavirina/administración & dosificación , Simeprevir/administración & dosificación , Sofosbuvir/administración & dosificación , Respuesta Virológica Sostenida , Valina/administración & dosificación , Valina/análogos & derivadosRESUMEN
Angiotensin II type 1 receptor agonist antibodies (AT1R-AAs) have been associated with hypertension, atherosclerosis and vascular inflammation in human diseases. The aim of the study was to evaluate the prevalence of AT1R-AAs in active lupus nephritis (LN) patients and their association with vascular damage. One hundred and seven active LN patients underwent a complete clinical examination, measurement of AT1R-AAs, ambulatory blood pressure monitoring, carotid intima-media thickness measurement and morphometric analysis of subintimal fibrosis and medial hyperplasia of the vessels in the kidney tissue. Plasma AT1R-AAs were positive in 58 (54.2%) patients. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, complement C3 and C4 levels and titers of anti-dsDNA antibodies were higher in the group with positive AT1R-AAs compared with those with negative AT1R-AAs. The AT1R-AA titers correlated with anti-dsDNA antibody titers and with complement C3 and C4 serum levels. In the kidney biopsy, the percentage of subintimal fibrosis and the area of medial hyperplasia were greater in the AT1R-AA-positive patients. No differences in arterial pressure, carotid intima-media thickness and response to therapy were detected. In conclusion, AT1R-AAs are prevalent in active LN patients and are associated with histologic features of microvascular damage.
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Autoanticuerpos/sangre , Riñón/irrigación sanguínea , Nefritis Lúpica/inmunología , Receptor de Angiotensina Tipo 1/agonistas , Adulto , Anticuerpos Antinucleares/sangre , Monitoreo Ambulatorio de la Presión Arterial/métodos , Grosor Intima-Media Carotídeo , Estudios de Casos y Controles , Complemento C3/análisis , Complemento C4/análisis , Femenino , Fibrosis/patología , Humanos , Hiperplasia/patología , Inmunosupresores/uso terapéutico , Riñón/patología , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/patología , Masculino , Microvasos/patología , PrevalenciaRESUMEN
INTRODUCTION/OBJECTIVES: Anti-dense fine speckled 70 (DFS70) autoantibodies were reported to be more prevalent in healthy individuals than those with autoimmune diseases such as systemic lupus erythematosus (SLE). We determined anti-DFS70 autoantibody prevalence in a Latin American cohort of patients with SLE and healthy individuals. METHODS: This study included 127 individuals with anti-nuclear antibodies (ANAs; > 1:160) suggesting the presence of anti-DFS70, including 64 patients with SLE and 63 healthy controls. The anti-DFS70 autoantibodies were determined by immunoadsorption using NOVA Lite® HEp-2 Select kit with DAPI. Negative fluorescence after adsorption with the DFS70 antigen indicated anti-DFS70 autoantibody positivity. RESULTS: The presence of anti-DFS70 autoantibodies was confirmed by indirect immunofluorescence in 21 (33.3%) healthy controls and 8 (12.5%) patients with SLE (p = 0.005). Among the anti-DFS70-positive patients with SLE, the most frequent compromise was renal involvement in six cases (75%), 4 patients (37.5%) were positive for anti-Sm, which was the most frequently associated antibody, and one patient (12.5%) was positive for anti-DNA. CONCLUSIONS: Anti-DFS70 autoantibodies might be considered a biomarker to differentiate patients with SLE from ANA-positive individuals without autoimmune diseases. KEY POINTS: ⢠In a Latin American cohort, the anti-DFS70 was higher in individuals without autoimmune diseases compared with that in patients with SLE.⢠The anti-DFS70 might have utility as a biomarker of exclusion in patients with non-specific clinical signs of AARDs.
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Proteínas Adaptadoras Transductoras de Señales/inmunología , Anticuerpos Antinucleares/sangre , Lupus Eritematoso Sistémico/sangre , Factores de Transcripción/inmunología , Adulto , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/inmunología , Biomarcadores/sangre , Estudios de Casos y Controles , Colombia , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/inmunología , Masculino , Prevalencia , Estudios Prospectivos , Estudios Seroepidemiológicos , Adulto JovenAsunto(s)
Anemia Ferropénica , Anticuerpos Antinucleares/sangre , Ciclofosfamida/uso terapéutico , Ectasia Vascular Antral Gástrica , Hemorragia Gastrointestinal , Gastroscopía/métodos , Esclerodermia Sistémica , Factores de Edad , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/etiología , Anemia Ferropénica/terapia , Antirreumáticos/uso terapéutico , Coagulación con Plasma de Argón/métodos , Coagulación con Plasma de Argón/estadística & datos numéricos , Brasil/epidemiología , Femenino , Ectasia Vascular Antral Gástrica/epidemiología , Ectasia Vascular Antral Gástrica/etiología , Ectasia Vascular Antral Gástrica/inmunología , Ectasia Vascular Antral Gástrica/terapia , Hemorragia Gastrointestinal/epidemiología , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Humanos , Terapia por Láser/métodos , Terapia por Láser/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/fisiopatología , Factores SexualesRESUMEN
OBJECTIVE: African-Brazilians comprise a group of blacks and "pardos." As racial differences can be associated with distinct presentations, we evaluated the clinical and serological associations of African-Brazilians with systemic sclerosis (SSc). METHODS: Sera from 260 adult SSc patients (203 whites and 57 African-Brazilians) were evaluated. Patients with overlap syndromes were excluded. Clinical and demographic data were obtained from an electronic register database. Laboratory analysis included the following: anti-CENP-A/CENP-B, Scl70, RNA polymerase III, Ku, fibrillarin, Th/To, PM-Scl75, and PM-Scl100 by line immunoassay and anti-nuclear antibodies (ANA) by indirect immunofluorescence (IIF) on HEp-2 cells. RESULTS: African-Brazilian SSc patients presented shorter disease duration (12.8 ± 6.5 vs. 15.9 ± 8.1 years, p = 0.009), higher frequency of nucleolar ANA pattern (28% vs. 13%, p = 0.008), and lower frequencies of centromeric ANA pattern (14% vs. 29%, p = 0.026) and CENP-B (18% vs. 34%, p = 0.017), as well as an association with severe interstitial lung disease (58% vs. 43%; p = 0.044). Further comparison of ethnic groups according to subsets revealed that diffuse SSc African-Brazilian patients presented higher frequency of pulmonary hypertension (p = 0.017), heart involvement (p = 0.037), nucleolar ANA pattern (p = 0.036), anti-fibrillarin antibodies (p = 0.037), and higher mortality (48% vs. 19%; p = 0.009). A different pattern was observed for the limited subset with solely a lower frequency of esophageal involvement (p = 0.050) and centromeric ANA pattern (p = 0.049). Survival analysis showed that African-Brazilians had a higher mortality, when adjusted for age, gender, and clinical subset (RR 2.06, CI 95% 1.10-3.83, p = 0.023). CONCLUSION: African-Brazilians have distinct characteristics according to clinical subset and an overall more severe SSc than whites, similar to the blacks from other countries.Key Points ⢠African-Brazilian SSc patients were associated with severe interstitial lung disease and nucleolar ANA pattern when compared to white SSc patients. ⢠When disease subsets were considered, African-Brazilian patients with diffuse SSc presented association with pulmonary hypertension, heart involvement, nucleolar ANA pattern, and anti-fibrillarin antibodies. ⢠White SSc patients were associated with centromeric ANA pattern. ⢠Survival analysis at 5, 10, 15, and 20 years, adjusted for age, gender, and disease subset, was significantly worse in African-Brazilian SSc patients.
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Anticuerpos Antinucleares/sangre , Población Negra , Enfermedades Pulmonares Intersticiales/epidemiología , Esclerodermia Sistémica/etnología , Esclerodermia Sistémica/inmunología , Adulto , Brasil/epidemiología , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Inmunoensayo , Masculino , Persona de Mediana Edad , Esclerodermia Sistémica/mortalidad , Análisis de Supervivencia , Población BlancaRESUMEN
INTRODUCTION AND OBJECTIVES: Connective tissue diseases are inflammatory, autoimmune diseases and threaten quality of life. To determine the relationship between staining patterns of antinuclear antibodies and antibodies against extractable nuclear antigens in patients with connective tissue disease. MATERIALS AND METHODS: Observational, basic, analytical and transversal study. Study conducted in the Immunology Service of the Arzobispo Loayza National Hospital between January 2017 and June 2017. We analyzed 291 samples of patients with CTD and for the detection of anti-nuclear antibody staining patterns, the immunological kit and observation with microscope of at 40X Immunofluorescence and for the detection of the antibodies against extractable nuclear antigens. The Immunoblot method was employed. Statistical analyses were carried out with the statistical package SPSS version 21 for Windows. We used the Pearson Chi-square test for the categorical variables, a value of p<0.05 was considered significant. RESULTS: There was a significant relationship p<0.05 of the homogeneous pattern, the mottled pattern with Anti-histones (p=0.000), Anti-nucleosomes (p=0.000), Anti-Ro 52 (p=0.000), Anti-SSA (p=0.001), Anti-SSB (p=0.003), Anti-dsDNA (p=0.000) with the Pearson Chi-square test. There was a significant relationship of p<0.05 of the centromeric pattern with Anti-Cenp B (p=0.000) with Fisherâ¿¿s exact statistic. CONCLUSIONS: There was a significant relationship between the anti-nuclear antibody staining patterns and the antibodies to the core extractable antigens in patients with systemic lupus erythematosus, Sjögrenâ¿¿s syndrome, Calcinosis, Raynaudâ¿¿s phenomenon, esophageal Dysmotility, sclerodactyly and Telangiectasia (CREST), Scleroderma and Polymyositis.
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Anticuerpos Antinucleares/sangre , Autoanticuerpos/sangre , Enfermedades del Tejido Conjuntivo/inmunología , Adulto , Antígenos Nucleares/inmunología , Enfermedades Autoinmunes/inmunología , Estudios Transversales , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Immunoblotting , Masculino , Persona de Mediana Edad , Perú/epidemiologíaRESUMEN
Electrochemical biosensors have shown great promise as useful point-of-care tests since they operate on electronic circuits which can be miniaturized and whose readout process can be easily automated. Here, we describe a method for the electrochemical sensing of antibodies directed against double-stranded DNA (α-dsDNA), which are often present at higher-than-normal levels in the sera of autoimmune disease patients. The method can be easily implemented in any lab and requires little investment in equipment, namely a potentiostat. An artificial reference serum sample containing known amounts of spiked-in α-dsDNA antibodies enables reporting results in absolute scale rather than titer. Once electrodes are modified with DNA and the calibration curves are made (i.e., after the biosensor construction phase), individual measurements in test samples can be obtained in as low as 35 min.
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Anticuerpos Antinucleares/sangre , Técnicas Biosensibles/métodos , ADN/inmunología , Técnicas Electroquímicas/métodos , Anticuerpos Antinucleares/inmunología , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/inmunología , Electrodos , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Pruebas en el Punto de Atención , Potenciometría/métodosRESUMEN
PURPOSE: Immune checkpoint inhibitors (ICIs) show promising clinical activity in advanced cancers. However, the safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies (ANA) are unclear. METHODS: 191 patients treated with nivolumab, pembrolizumab, atezolizumab, or durvalumab for unresectable advanced cancers between September 2014 and December 2018 were identified retrospectively. Patients were divided into positive (ANA titers ≥ 1:160) and negative ANA groups (ANA titers < 1:160). Development of immune-related adverse events (irAEs), the overall response rate (ORR), and disease control rate (DCR) were monitored. RESULTS: Positive ANA titers were seen in 9 out of 191 patients. Four patients in the positive ANA group and 69 patients in the negative group developed irAEs of any grade without a significant difference between the groups. The development of endocrine, pulmonary, and cutaneous irAEs was not significant, whereas positive ANA was significantly higher in patients who developed colitis (2/9) than in patients who did not (3/182, P = 0.0002). DCR in the positive and negative ANA group was 37.5% and 67.5%, respectively, and was not statistically significant, but had better efficacy in patients without ANA (P = 0.08). ANA-related autoimmune diseases such as SLE, Sjögren's syndrome, MCTD, scleroderma, dermatomyositis, and polymyositis was not induced in either group. However, one patient with preexisting dermatomyositis had a flare up after initiation of atezolizumab. CONCLUSION: Further studies to identify predictive factors for the development of irAEs are required to provide relevant patient care and maximize the therapeutic benefits of ICIs.
Asunto(s)
Anticuerpos Antinucleares/sangre , Antineoplásicos Inmunológicos/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/antagonistas & inhibidores , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/sangre , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
To assess the presence of persistent serological activity and its association with clinical outcomes in primary Sjögren's syndrome. Clinical charts of 275 patients were reviewed retrospectively. Persistent serological activity was defined as an increase IgG ≥ 1.6 mg/dL or globulins > 3.7 g/dL or diminished C3 < 52 mg/dL or C4 < 12 mg/dL at least during two consecutive visits during a year (index period). The ClinESSDAI at the index period and the cumulative ClinESSDAI and the SSDDI at the last medical appointment were scored. A total of 159 patients with complete serological data were included mostly women and median disease duration of 10.2 years. Persistent serological activity was identified in 85 patients (53.1%). Only 13 patients changed their status to serological inactivity though the follow-up. Comparison of patients with (n = 85) versus without persistent serological activity (n = 74) showed that the first group had a higher frequency of impaired non-stimulated salivary flow, anti-La/SSB antibody, and RF, as well as higher ClinESSDAI scores. The most affected domains were the constitutional, glandular, cutaneous, renal, and hematological domains. On logistic regression analysis, the RF (OR 6.4, 95% CI 1.8-22, p = 0.003), the renal (OR 12.8, 95% CI 1.7-92, p = 0.01), and the hematological involvement (OR 4.7, 95% CI 1.6-13.4, p = 0.004) remained associated. Half of the patients studied had persistent serological activity, being this status constant through the follow-up. Persistent serological activity was associated with positive RF and higher ESSDAI scores due to hematological and renal activity. Scoring serological activity is an important issue in SS patients.
Asunto(s)
Anticuerpos Antinucleares/sangre , Índice de Severidad de la Enfermedad , Síndrome de Sjögren/diagnóstico , Adulto , Anciano , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Síndrome de Sjögren/sangreRESUMEN
Background: Diabetes mellitus type 1 (T1DM) is one of the childhood diseases with growing prevalence. Various accompanying autoimmune diseases were seen with type 1 diabetes. The most common autoimmune diseases with T1DM are autoimmune thyroiditis and celiac disease. In some reports, autoimmune hepatitis has been reported in association with DM-1. Objectives: The aim of this study was to evaluate autoimmune hepatitis autoantibodies in children with T1DM. Materials and methods: In this crosssectional study, 202 children with T1DM were evaluated (47.5% were males and 52.5% were girls). Liver enzymes, autoimmune hepatitis related autoantibodies such as anti-nuclear antibodies (ANA), anti-smooth muscle (ASMA) and anti liver and kidney microsomal antibodies (LKM-1) were measured. Liver ultrasound was done for participants and biopsy of liver was taken for children with increased echogenicity of the liver, hepatomegaly or elevated liver enzymes. Results analyzed by statistical software spss-16, Descriptive statistics and chi-square test, paired T-TEST. Level of less than 5% was considered statistically significant. Results: In 6 patients ANA and in 4 patients (2%) ASMA was positive,1 patient was ASMA positive but ANA negative. None of the patients were Anti LKM-1 positive. 3 patients had positive ANA and ASMA, and increased liver echogenicity on ultrasound simultaneously. Histological evaluation was showed that 2 patients had findings in favor of autoimmune hepatitis. Conclusion: Auto antibodies were positive in 10 cases. ANA was positive in 6 (2.97%) of all cases. ASMA was positive in 4 (1.98%) cases. Increased echogenicity was found in 3 cases. Histological evaluation showed 2 patients had biopsy confirmed autoimmune hepatitis. AIH-2 was not seen among our cases.
Antecedentes: La diabetes mellitus tipo 1 (DM1) es una de las enfermedades infantiles con mayor prevalencia. Se observaron varias enfermedades autoinmunes acompañantes con diabetes tipo 1. Las enfermedades autoinmunes más comunes con DM1 son la tiroiditis autoinmune y la enfermedad celíaca. En algunos reportes, se ha encontrado hepatitis autoinmune en asociación con DM-1. Objetivos: El objetivo de este estudio fue evaluar los autoanticuerpos de hepatitis autoinmunes en niños con DM1. Materiales y métodos: En este estudio transversal, se evaluaron 202 niños con DM1 (47,5% eran hombres y 52,5% eran niñas). Se midieron las enzimas hepáticas, los autoanticuerpos autoinmunes relacionados con la hepatitis, como los anticuerpos antinucleares (ANA), el músculo liso (ASMA) y los anticuerpos microsomales hepáticos y renales (LKM-1). Se realizó una ecografía hepática para los participantes y se tomó una biopsia del hígado para niños con mayor ecogenicidad del hígado, hepatomegalia o enzimas hepáticas elevadas. Los resultados fueron analizados por el software estadístico spss-16 usando estadística descriptiva y prueba de chi-cuadrado, T-TEST pareado. Se consideró estadísticamente significativo un nivel menor del 5%. Resultados: En 6 pacientes con ANA y en 4 pacientes (2%) ASMA fue positiva, 1 paciente fue ASMA positiva pero ANA negativa. Ninguno de los pacientes fue anti LKM-1 positivo. 3 pacientes tuvieron ANA y ASMA positivas, y aumentaron la ecogenicidad hepática en la ecografía simultáneamente. La evaluación histológica mostró que 2 pacientes tenían hallazgos a favor de la hepatitis autoinmune. Conclusión: Los autoanticuerpos fueron positivos en 10 casos. ANA fue positivo en 6 (2,97%) de todos los casos. La ASMA fue positiva en 4 (1,98%) casos. Se encontró mayor ecogenicidad en 3 casos. La evaluación histológica mostró que 2 pacientes tenían biopsia confirmada de hepatitis autoinmune. AIH-2 no fue visto entre nuestros casos.
Asunto(s)
Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Adulto Joven , Autoanticuerpos/sangre , Hepatitis Autoinmune/inmunología , Diabetes Mellitus Tipo 1/inmunología , Aspartato Aminotransferasas/sangre , Microsomas Hepáticos/inmunología , Anticuerpos Antinucleares/sangre , Estudios Transversales , Alanina Transaminasa/sangre , Riñón/inmunología , Microsomas/inmunología , Músculo Liso/inmunologíaRESUMEN
Current treatments for systemic autoimmune diseases partially improve the health of patients displaying low pharmacological efficacy and systemic immunosuppression. Here, the therapeutic potential of transferring tolerogenic dendritic cells (tolDCs) generated with heme-oxygenase inductor cobalt (III) protoporphyrin IX (CoPP), dexamethasone and rosiglitazone for the treatment of systemic autoimmunity was evaluated in two murine models of systemic lupus erythematosus (SLE), MRL-Faslpr and NZM2410 mice. Dendritic cells treated ex vivo with these drugs showed a stable tolerogenic profile after lipopolysaccharide stimulation. Regular doses of tolDCs were administered to anti-nuclear antibody-positive mice throughout 60-70 days, and the clinical score was evaluated. Long-term treatment with these tolDCs was well tolerated and effective to improve the clinical score on MRL-Faslpr lupus-prone mice. Additionally, decreased levels of anti-nuclear antibodies in NZM2410 mice were observed. Although tolDC treatment increased regulatory T cells, no significant reduction of renal damage or glomerulonephritis could be found. In conclusion, these results suggest that the transfer of histone-loaded tolDCs could improve only some SLE symptoms and reduced anti-nuclear antibodies. This is the first study to evaluate antigen-specific tolDC administration to treat SLE. Our report strengthens the clinical relevance of tolDC generation with CoPP, dexamethasone and rosiglitazone and the use of these modified cells as a therapy for systemic autoimmunity.
Asunto(s)
Células Dendríticas/inmunología , Inmunoterapia Adoptiva/métodos , Riñón/patología , Lupus Eritematoso Sistémico/terapia , Linfocitos T Reguladores/inmunología , Animales , Anticuerpos Antinucleares/sangre , Diferenciación Celular , Células Cultivadas , Células Dendríticas/trasplante , Dexametasona/metabolismo , Modelos Animales de Enfermedad , Humanos , Tolerancia Inmunológica , Lupus Eritematoso Sistémico/inmunología , Activación de Linfocitos , Ratones , Ratones Endogámicos MRL lpr , Pirazinas/metabolismo , Pirroles/metabolismo , Rosiglitazona/metabolismoRESUMEN
Abstract Objective: This large study with a long-term follow-up aimed to evaluate the clinical presentation, laboratory findings, histological profile, treatments, and outcomes of children and adolescents with autoimmune hepatitis. Methods: The medical records of 828 children and adolescents with autoimmune hepatitis were reviewed. A questionnaire was used to collect anonymous data on clinical presentation, biochemical and histological findings, and treatments. Results: Of all patients, 89.6% had autoimmune hepatitis-1 and 10.4% had autoimmune hepatitis-2. The female sex was predominant in both groups. The median age at symptom onset was 111.5 (6; 210) and 53.5 (8; 165) months in the patients with autoimmune hepatitis 1 and autoimmune hepatitis-2, respectively. Acute clinical onset was observed in 56.1% and 58.8% and insidious symptoms in 43.9% and 41.2% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively. The risk of hepatic failure was 1.6-fold higher for autoimmune hepatitis-2. Fulminant hepatic failure occurred in 3.6% and 10.6% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively; the risk was 3.1-fold higher for autoimmune hepatitis-2. The gamma globulin and immunoglobulin G levels were significantly higher in autoimmune hepatitis-1, while the immunoglobulin A and C3 levels were lower in autoimmune hepatitis-2. Cirrhosis was observed in 22.4% of the patients; biochemical remission was achieved in 76.2%. The actuarial survival rate was 93.0%. A total of 4.6% underwent liver transplantation, and 6.9% died (autoimmune hepatitis-1: 7.5%; autoimmune hepatitis-2: 2.4%). Conclusions: In this large clinical series of Brazilian children and adolescents, autoimmune hepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higher disease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death.
Resumo Objetivo: Este estudo com acompanhamento de longo prazo visou a avaliar o quadro clínico, os achados laboratoriais, o perfil histológico, os tratamentos e os resultados de crianças e adolescentes com hepatite autoimune. Métodos: Foram analisados os prontuários médicos de 828 crianças e adolescentes com HAI. Foi usado um questionário para coletar os dados anônimos sobre o quadro clínico, os achados bioquímicos e histológicos e os tratamentos. Resultados: De todos os pacientes, 89,6% tinham hepatite autoimune-1 e 10,4% hepatite autoimune-2. O sexo feminino foi predominante nos dois grupos. A idade média no início dos sintomas foi 111,5 (6; 210) e 53,5 (8; 165) meses nos pacientes com hepatite autoimune-1 e hepatite autoimune-2, respectivamente. Foi observado início clínico agudo em 56,1% e 58,8% e sintomas insidiosos em 43,9% e 41,2% dos pacientes com hepatite autoimune-1 e hepatite autoimune-2, respectivamente. A probabilidade de insuficiência hepática foi 1,6 vezes maior para hepatite autoimune-2; 3,6% e 10,6% dos pacientes com hepatite autoimune-1 e hepatite autoimune-2, respectivamente, apresentaram insuficiência hepática fulminante; o risco foi 3,1 vezes maior para hepatite autoimune-2. Os níveis de gamaglobulina e imunoglobulina G foram significativamente maiores nos pacientes com hepatite autoimune-1, ao passo que os níveis de imunoglobulina A e C3 foram menores em pacientes com hepatite autoimune-2; 22,4% dos pacientes apresentaram cirrose e a remissão bioquímica foi atingida em 76,2%. A taxa de sobrevida atuarial foi de 93,0%. Um total de 4,6% pacientes foram submetidos a transplante de fígado e 6,9% morreram (hepatite autoimune-1: 7,5%; hepatite autoimune-2: 2,4%). Conclusões: Nesta grande série clínica de crianças e adolescentes brasileiros, a hepatite autoimune-1 foi mais frequente e os pacientes com hepatite autoimune-2 mostraram maiores taxas de remissão da doença com respostas mais rápidas aos tratamentos. Os pacientes com hepatite autoimune-1 apresentaram maior risco de óbito.