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Rheumatoid Arthritis (RA) is a multifactorial autoimmune disease. Currently, several genes play an important role in the development of the disease. The objective was to evaluate the association of the STAT4 rs7574865 and rs897200 gene variants with RA susceptibility, DAS28, RF, and anti-CCP in Western and Southern Mexico populations. Genotyping was performed on 476 samples (cases = 240; controls = 236) using the Taqman® system and qPCR probes. Disease activity was assessed using DAS28 and HAQ DI. CRP, ESR, RF, and anti-CCP were determined for clinical assessment. Our study showed there is a statistically significant association with susceptibility to RA for the rs7574865 variant in the Western population for the GT and TT genotypes. The same genotypes also showed a moderate-to-high activity according to DAS28 and positive anti-CCP compared to the control group. This association was not found in the Southern population. This work confirms the association of the rs7574865 variant with RA, as well as a moderate-to-high activity and positive anti-CCP in the Western population but not in the Southern population. No association of the rs897200 variant was found in any of the studied populations.
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Anticorpos Antiproteína Citrulinada , Artrite Reumatoide , Humanos , México , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Artrite Reumatoide/genética , Fator de Transcrição STAT4/genéticaRESUMO
We report clinical, serologic, and immunogenetic studies of a set of monozygotic male twin patients who develop autoimmune thyroiditis and vitiligo associated with the HLA-DRB1*04-DQB1*03:02 and HLA-DRB1*03-DQB1*0201 haplotypes. The patients had detectable anti-thyroid and anti-melanocyte autoantibodies. A critical review is presented regarding the role of MHC II molecules linked to clinical manifestations of various autoimmune diseases displayed in a single patient, as is the case in the twin patients reported here.
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The pathogenesis of Rheumatoid Arthritis (RA) is not fully understood, probably influenced by genetic and environmental factors. Interstitial Lung Disease (ILD) is an extra-articular manifestation of RA, which contributes significantly to morbidity and mortality. The identification of anti-HLA antibodies has been useful in the transplantation field; however, its contribution to autoimmune diseases as RA has not been fully studied. We aimed to determine the presence of anti-HLA antibodies in RA patients with and without ILD and its possible association with clinical and biochemical markers. One-hundred and forty-seven RA patients, of which 65 had ILD (RA-ILD group), were included. Sera samples for Anti-HLA Class II LABScreen panel-reactive antibodies (PRA) were analyzed. In both groups, women predominated, and lung function was worse in patients with ILD. The anti-CCP+ (UI/mL) was higher in the RA group in comparison to RA-ILD (p < 0.001). Expositional risk factors (tobacco smoking and biomass-burning smoke) were higher in RA-ILD patients. PRA+ was identified in ~25% RA-ILD patients, while ~29% in the RA group. The CRP levels have a positive correlation with the percentage of reactivity (%PRA, p = 0.02, r2 = 0.60) in the RA-ILD group. In conclusion, anti-HLA antibodies correlate with C-reactive protein levels in RA patients with ILD.
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Artrite Reumatoide/imunologia , Autoanticorpos/sangue , Proteína C-Reativa/biossíntese , Doenças Pulmonares Intersticiais/imunologia , Adulto , Artrite Reumatoide/complicações , Biomarcadores/sangue , Feminino , Humanos , Doenças Pulmonares Intersticiais/complicações , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial membrane damage and autoantibody production. RA is a heterogeneous disease, where cytokines such as IL-15, IL-21, and IFN-γ have been associated. However, their association with the autoantibodies has not been clearly described. The aim of this study was to evaluate the relationship between the cytokines IL-15, IL-21, and IFN-γ with the autoantibodies (RF, anti-CCP, anti-MCV, and anti-PADI4) in RA and disease activity. METHODOLOGY: This study included 153 RA patients and 80 control subjects (CS). The levels of IL-15, IL-21, IFN-γ, anti-CCP, anti-MCV, and anti-PADI4 were quantified by ELISA, whereas RF was quantified by turbidimetry. The disease activity was evaluated by the indices disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR), clinical disease activity index (CDAI), and simple disease activity index (SDAI). RESULTS: The serum levels of IL-15, IL-21, and IFN-γ, and autoantibodies were increased in RA patients, compared with CS (p < 0.05). A correlation was found between IL-21 and anti-CCP and anti-MCV (p < 0.05). According to RA evolution, RF, anti-CCP, and anti-MCV had higher levels in early RA. In addition, increased levels of IL-21 were observed in RA seropositive patients (RF/anti-CCP/anti-MCV). The higher levels of both cytokines and autoantibodies were observed in moderate activity, evaluated by the three indices. CONCLUSIONS: Our results suggest that the increased soluble levels of IL-15, IL-21, and IFN-γ are involved in the inflammatory network in RA. However, IL-21 serum levels are associated with higher titers of autoantibodies (RF, anti-CCP, and anti-MCV) and IL-15 with moderate activity. Key Points ⢠IL-15, IL-21, and IFN-y are associated with the immunopathology of RA, but not significantly with the evolution of the disease. ⢠RF, anti-CCP, and anti-MCV had higher levels in early than established RA. ⢠IL-21 has an association with RF, anti-CCP, and anti-MCVand, for this reason, could be proposed as a disease biomarker. ⢠Patients with activity moderate of disease showed higher levels of RF, anti-CCP, anti-MCV, and IL-15.
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Artrite Reumatoide/sangue , Autoanticorpos/sangue , Citocinas/sangue , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto JovemRESUMO
Rheumatoid arthritis is a clinical autoimmune syndrome that causes joint damage. The positive or negative anti-cyclic citrullinated protein (CCP) antibodies serodiagnosis differentiates two subsets of the disease, each with different genetic background. Previous studies have identified associations between KIR genes and rheumatoid arthritis but not with anti-CCP serodiagnosis. Therefore, we investigated the proportion of patients seropositive and seronegative to anti-CCP and its possible association with KIR (killer cell immunoglobulin-like receptor) genes. We included 100 patients with rheumatoid arthritis from western Mexico, who were determined for anti-CCP serodiagnosis by ELISA, and 16 KIR genes were genotyped by PCR-SSP. The proportion of seropositive anti-CCP patients was 83%, and they presented a higher frequency of KIR2DL2 genes than the seronegative group (73.6% vs. 46.2%, p = 0.044) which, in turn, presented a higher KIR2DL2-/KIR2DL3+ genotype frequency than the first ones (46.2% vs. 17.2%, p = 0.043). These results suggest different KIR genetic backgrounds for each subset of the disease according to anti-CCP serodiagnosis.
La artritis reumatoide es un síndrome clínico autoinmune que causa daño en las articulaciones. El serodiagnóstico positivo o negativo para anticuerpos proteicos anticíclicos citrulinados (CCP) diferencia dos subconjuntos de la enfermedad, cada uno con diferente fondo genético. Estudios previos han identificado asociaciones entre los genes killer cell immunoglobulin- like receptor (KIR) y la artritis reumatoide, pero no con el serodiagnóstico de anti-CCP. Por lo tanto, investigamos la proporción de seropositividad y seronegatividad anti-CCP y su posible asociación con genes KIR. Se incluyeron 100 pacientes con artritis reumatoide del occidente de México, a quienes se les determinó su serodiagnóstico anti-CCP por ELISA y también se les realizó genotipificación de 16 genes KIR por PCR-SSP. La proporción de pacientes seropositivos anti-CCP fue del 83% y presentaron una mayor frecuencia génica KIR2DL2 que el grupo seronegativo (73.6% vs. 46.2%, p = 0.044), estos últimos presentaron mayor frecuencia genotípica KIR2DL2-/KIR2DL3+ que los primeros (46.2% vs. 17.2%, p = 0.043). Los resultados sugieren diferente fondo genético KIR para cada subconjunto de la enfermedad, de acuerdo con el serodiagnóstico anti-CCP.
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Artrite Reumatoide/diagnóstico , Autoanticorpos/sangue , Receptores KIR2DL2/genética , Adulto , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/genética , Autoanticorpos/genética , Feminino , Genótipo , Humanos , Masculino , México , Pessoa de Meia-Idade , Fator Reumatoide/sangueRESUMO
Rheumatoid arthritis is a clinical autoimmune syndrome that causes joint damage. The positive or negative anti-cyclic citrullinated protein (CCP) antibodies serodiagnosis differentiates two subsets of the disease, each with different genetic background. Previous studies have identified associations between KIR genes and rheumatoid arthritis but not with anti-CCP serodiagnosis. Therefore, we investigated the proportion of patients seropositive and seronegative to anti-CCP and its possible association with KIR (killer cell immunoglobulin-like receptor) genes. We included 100 patients with rheumatoid arthritis from western Mexico, who were determined for anti-CCP serodiagnosis by ELISA, and 16 KIR genes were genotyped by PCR-SSP. The proportion of seropositive anti-CCP patients was 83%, and they presented a higher frequency of KIR2DL2 genes than the seronegative group (73.6% vs. 46.2%, p = 0.044) which, in turn, presented a higher KIR2DL2-/ KIR2DL3+ genotype frequency than the first ones (46.2% vs. 17.2%, p = 0.043). These results suggest different KIR genetic backgrounds for each subset of the disease according to anti-CCP serodiagnosis.
La artritis reumatoide es un síndrome clínico autoinmune que causa daño en las articulaciones. El serodiagnóstico positivo o negativo para anticuerpos proteicos anti-cíclicos citrulinados (CCP) diferencia dos subconjuntos de la enfermedad, cada uno con diferente fondo genético. Estudios previos han identificado asociaciones entre los genes killer cell immunoglobulin- like receptor (KIR) y la artritis reumatoide, pero no con el serodiagnóstico de anti-CCP. Por lo tanto, investigamos la proporción de seropositividad y seronegatividad anti-CCP y su posible asociación con genes KIR. Se incluyeron 100 pacientes con artritis reumatoide del occidente de México, a quienes se les determinó su serodiagnóstico anti-CCP por ELISA y también se les realizó genotipificación de 16 genes KIR por PCR-SSP. La proporción de pacientes seropositivos anti-CCP fue del 83% y presentaron una mayor frecuencia génica KIR2DL2 que el grupo seronegativo (73.6% vs. 46.2%, p = 0.044), estos últimos presentaron mayor frecuencia genotípica KIR2DL2-/KIR2DL3+ que los primeros (46.2% vs. 17.2%, p = 0.043). Los resultados sugieren diferente fondo genético KIR para cada subconjunto de la enfermedad, de acuerdo con el serodiagnóstico anti-CCP.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Artrite Reumatoide/diagnóstico , Autoanticorpos/sangue , Receptores KIR2DL2/genética , Artrite Reumatoide/genética , Artrite Reumatoide/sangue , Fator Reumatoide/sangue , Autoanticorpos/genética , Genótipo , MéxicoRESUMO
Rheumatoid arthritis (RA) is a chronic T cell-mediated autoimmune disease. Serum autoantibodies against cyclic citrullinated peptides (anti-CCP) are significant markers for diagnosis and prognosis of this disease. Induction of immune tolerance as therapeutic approach for RA constitutes a current research focal point. In this sense, we carried out a phase I clinical trial in RA patients with a new therapeutic candidate (called CIGB-814); which induced mechanisms associated with restoration of peripheral tolerance in preclinical studies. CIGB 814 is an altered peptide ligand (APL), derived from a CD4+ T cell epitope of human heat-shock protein 60 (HSP60), an autoantigen involved in the pathogenesis of RA. Twenty patients with moderate disease activity were included in this open label trial. Sequential dose-escalation of 1, 2.5 and 5 mg of CIGB-814 was studied. Consecutive groups of six, five, and nine patients received a subcutaneous dose weekly of the peptide during the first month and one dose monthly during the next 5 months. The peptide was well tolerated and reduced disease activity. Here, we reported the quantification of anti-CCP antibodies during the treatment with this APL and in the follow-up stage. Anti-CCP antibodies were quantified in the plasma from patients by a commercial enzyme immunoassay at baseline (T0) and at weeks 28 and 48. Results showed that CIGB-814 induced a significant reduction of anti-CCP antibodies. In addition, this decrease correlated with clinical improvement in patients assessed by Disease Activity Score in 28 joints (DAS28) criteria. These findings reinforce the therapeutic potential of CIGB-814.
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Artrite Reumatoide/tratamento farmacológico , Chaperonina 60/química , Proteínas Mitocondriais/química , Peptídeos/administração & dosagem , Adulto , Anticorpos Antiproteína Citrulinada/imunologia , Artrite Reumatoide/imunologia , Artrite Reumatoide/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos/uso terapêutico , Peptídeos Cíclicos/imunologia , Resultado do TratamentoRESUMO
Introducción: La artritis reumatoide es una enfermedad autoinmune caracterizada por la presencia de anticuerpos contra péptidos citrulinados, que constituyen indicadores para el diagnóstico de la enfermedad. Es necesario determinar la utilidad de diferentes métodos de determinación de estos anticuerpos para el diagnóstico de pacientes cubanos con artritis reumatoide. Objetivo: Determinar la eficacia de los ensayos de determinación de anticuerpos anti-CCP2 y anti-CCP3 para el diagnóstico de pacientes cubanos con artritis reumatoide. Material y método: Participaron 101 pacientes con artritis reumatoide, 58 pacientes con otras enfermedades reumáticas e inflamatorias y 43 individuos sanos. Se determinó la eficacia diagnóstica de los anticuerpos factor reumatoideo (FR), anti-CCP2 y anti-CCP3 medidos mediante ELISA, con el cálculo de la sensibilidad, especificidad, valores predictivos positivos y negativos. Resultados: El ensayo anti-CCP2 mostró un mejor balance sensibilidad (48,5 por ciento) y especificidad (98,0 por ciento). Cuando se fijó la especificidad a 98 por ciento, se observó la menor sensibilidad para el FR (40,3 por ciento). Utilizar los ensayos anti-CCP2 y FR aumentó la especificidad a 100 por ciento. Todos los autoanticuerpos mostraron asociación con la proteína C reactiva y correlación con la velocidad de sedimentación globular. Solamente los anticuerpos anti-CCP2 no mostraron correlación con el indicador clínico de actividad DAS 28. Conclusiones: Los anticuerpos anti-CCP2 son los de mayor eficacia para el diagnóstico de pacientes cubanos con artritis reumatoide. La determinación de FR permite identificar pacientes con artritis reumatoide seronegativos de anticuerpos anti-CCP2, por lo que la combinación de ambos inmunoensayos produce una mejoría en la eficacia diagnóstica(AU)
Introduction: Rheumatoid arthritis is an autoimmune disease characterized by the presence of antibodies against citrullinated peptides, which are one of the indicators for the diagnosis of a disease. The usefulness of different methods for the determination of these antibodies in the diagnosis of Cuban patients with rheumatoid arthritis is necessary to be established. Objective: To establish the diagnostic effectiveness of the second (anti-CCP2) and third (anti-CCP3) generation assays for the determination these antibodies against citrullinated peptides in Cuban patients with rheumatoid arthritis. Material and method: 101 patients with rheumatoid arthritis, 58 patients with other rheumatic and inflammatory diseases, and 43 healthy persons participated in the study. The diagnostic efficiency of rheumatoid factor (RF), anti-CCP2 and anti-CCP3 antibodies were determined using ELISA test, by calculating sensitivity, specificity, and positive and negative predictive values. Results: The anti-CCP2 assay showed a better balance of sensitivity (48.5 percent) and specificity (98.0 percent). The lower sensibility was observed for RF (40.3 percent) when the specificity was set at 98 percent. Specificity increased to 100 percent when anti-CCP2 and RF assays were used. All autoantibodies showed association with C-reactive protein and correlation with erythrocyte sedimentation rate. Only anti-CCP2 antibodies showed no correlation with the DAS28 clinical indicator. Conclusions: Anti-CCP2 antibodies are the ones of greater effectiveness in the diagnosis of Cuban patients with rheumatoid arthritis. RF identification allows to identify seronegative anti-CCP2 patients; therefore, the combination of both immunoassays leads to an improvement in the diagnostic effectiveness(AU)
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Humanos , Masculino , Feminino , Artrite Reumatoide/diagnóstico , Técnicas e Procedimentos Diagnósticos/normas , Anticorpos Antiproteína Citrulinada/imunologia , Estudos de Casos e Controles , Anticorpos Antiproteína Citrulinada/uso terapêutico , AnticorposRESUMO
La enfermedad de Still del adulto (ESA) es un proceso inflamatorio sistémico, de etiología desconocida, que se caracteriza por fiebre, artritis y eritema evanescente, además de valores elevados de ferritina sérica. Sin embargo, hasta la fecha, no hay una prueba definitiva de laboratorio o de imagen disponible para su diagnóstico, por lo tanto la ESA es un diagnóstico de exclusión. Presentamos el caso de una mujer de 44 años con manifestación cutánea atípica de ESA y cuadro clínico de 1 año de evolución caracterizado por fiebre de 40°C, linfadenopatía, hiperferritinemia, y que en la sistemática de estudio presentó positividad para anti-CCP (anticuerpo antipéptido cíclico citrulinado).
Adult Still's disease (ASD) is a systemic inflammatory process, of unknown etiology, characterized by fever, arthritis and evanescent erythema, in addition to elevated serum ferritin values. However, to date, there is no definitive laboratory or imaging test available to diagnose it, therefore ASD is a diagnosis of exclusion. We present the case of a 44-year-old woman with atypical cutaneous manifestation of ESA and positivity of ACPA (anti-cyclic citrullinated peptide antibody).
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Doença de Still de Início Tardio , Ferritinas , Anticorpos Antiproteína CitrulinadaRESUMO
ABSTRACT Objectives: To evaluate the frequency of four serum biomarkers in RA patients and their relatives and identify possible associations with clinical findings of the disease. Methods: This was a transversal analytical study. Anti-cyclic citrullinated peptide (anti-CCP), anti-mutated citrullinated vimentin (anti-MCV) and IgA-rheumatoid factor (RF) were determined by ELISA and IgM-RF by latex agglutination in 210 RA patients, 198 relatives and 92 healthy controls from Southern Brazil. Clinical and demographic data were obtained through charts review and questionnaires. Results: A higher positivity for all antibodies was observed in RA patients when compared to relatives and controls (p < 0.0001). IgA-RF was more frequent in relatives compared to controls (14.6% vs. 5.4%, p = 0.03, OR = 2.98; 95% CI = 1.11-7.98) whereas anti-CCP was the most common biomarker among RA patients (75.6%). Concomitant positivity for the four biomarkers was more common in patients (46.2%, p < 0.0001). Relatives and controls were mostly positive for just one biomarker (20.2%, p < 0.0001 and 15.2%, p = 0.016, respectively). No association was observed between the number of positive biomarkers and age of disease onset, functional class or tobacco exposure. In seronegative patients predominate absence of extra articular manifestations (EAMs) (p = 0.01; OR = 3.25; 95% CI = 1.16-10.66). Arthralgia was present in positive relatives, regardless the type of biomarker. Conclusions: A higher number of biomarkers was present in RA patients with EAMs. Positivity of biomarkers was related to arthralgia in relatives. These findings reinforce the link between distinct biomarkers and the pathophysiologic mechanisms of AR.
RESUMO Objetivos: Avaliar a frequência de quatro marcadores sorológicos em pacientes com AR e seus familiares e identificar possíveis associações com achados clínicos da doença. Métodos: Estudo analítico transversal. Determinaram-se os níveis de anticorpos antipeptídeo citrulinado cíclico (anti-CCP), anticorpos antivimentina citrulinada-mutada (anti-MCV) e fator reumatoide (FR) IgA por Elisa e de FR-IgM por aglutinação em látex em 210 pacientes com AR, 198 familiares e 92 controles saudáveis do sul do Brasil. Coletaram-se dados clínicos e demográficos por meio da revisão de prontuários e questionários. Resultados: Observou-se maior positividade para todos os anticorpos em pacientes com AR em comparação com os familiares e controles (p < 0,0001). O FR-IgA era mais frequente em familiares quando comparados com os controles (14,6% versus 5,4%, p = 0,03, OR = 2,98; IC95% = 1,11 a 7,98). O anti-CCP foi o biomarcador mais comum entre pacientes com AR (75,6%). A positividade concomitante para os quatro biomarcadores foi mais comum nos pacientes (46,2%, p < 0,0001). Familiares e controles eram positivos em sua maioria para apenas um biomarcador (20,2%, p < 0,0001 e 15,2%, p = 0,016, respectivamente). Não foi observada associação entre o número de biomarcadores positivos e a idade de início da doença, classe funcional ou exposição ao fumo. Em pacientes soronegativos, predominou a ausência de manifestações extra-articulares (MEA) (p = 0,01; OR = 3,25; IC95% = 1,16 a 10,66). A artralgia estava presente em familiares positivos, independentemente do tipo de biomarcador. Conclusões: Um maior número de biomarcadores estava presente em pacientes com AR com MEA. A positividade dos biomarcadores estava relacionada com a artralgia em familiares. Esses achados reforçam a ligação entre os diferentes biomarcadores e os mecanismos fisiopatológicos da AR.
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Humanos , Masculino , Feminino , Adulto , Artrite Reumatoide/sangue , Fator Reumatoide/sangue , Vimentina/sangue , Anticorpos Antiproteína Citrulinada/sangue , Artrite Reumatoide/classificação , Artrite Reumatoide/complicações , Ensaio de Imunoadsorção Enzimática , Biomarcadores/sangue , Estudos de Casos e Controles , Artralgia/etiologia , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: To evaluate the frequency of four serum biomarkers in RA patients and their relatives and identify possible associations with clinical findings of the disease. METHODS: This was a transversal analytical study. Anti-cyclic citrullinated peptide (anti-CCP), anti-mutated citrullinated vimentin (anti-MCV) and IgA-rheumatoid factor (RF) were determined by ELISA and IgM-RF by latex agglutination in 210 RA patients, 198 relatives and 92 healthy controls from Southern Brazil. Clinical and demographic data were obtained through charts review and questionnaires. RESULTS: A higher positivity for all antibodies was observed in RA patients when compared to relatives and controls (p<0.0001). IgA-RF was more frequent in relatives compared to controls (14.6% vs. 5.4%, p=0.03, OR=2.98; 95% CI=1.11-7.98) whereas anti-CCP was the most common biomarker among RA patients (75.6%). Concomitant positivity for the four biomarkers was more common in patients (46.2%, p<0.0001). Relatives and controls were mostly positive for just one biomarker (20.2%, p<0.0001 and 15.2%, p=0.016, respectively). No association was observed between the number of positive biomarkers and age of disease onset, functional class or tobacco exposure. In seronegative patients predominate absence of extra articular manifestations (EAMs) (p=0.01; OR=3.25; 95% CI=1.16-10.66). Arthralgia was present in positive relatives, regardless the type of biomarker. CONCLUSIONS: A higher number of biomarkers was present in RA patients with EAMs. Positivity of biomarkers was related to arthralgia in relatives. These findings reinforce the link between distinct biomarkers and the pathophysiologic mechanisms of AR.
Assuntos
Anticorpos Antiproteína Citrulinada/sangue , Artrite Reumatoide/sangue , Fator Reumatoide/sangue , Vimentina/sangue , Adulto , Artralgia/etiologia , Artrite Reumatoide/classificação , Artrite Reumatoide/complicações , Biomarcadores/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The peptidyl arginine deiminase type IV (PADI4) gene has been associated with RA susceptibility in several populations. We addressed the relationship between three exonic PADI4 gene single nucleotide polymorphisms (SNPs) PADI4_89 (rs11203366), PADI4_90 (rs11203367) and PADI4_92 (rs874881) and related haplotypes with RA in a population from Southern México. This study included 200 RA patients and 200 control subjects. The SNPs were evaluated using the polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) technique, and antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). In this population, the minor alleles of PADI4_89∗G, PADI4_90∗T and PADI4_92∗G gene polymorphisms were associated with RA susceptibility (OR=1.34, p=0.04; OR=1.35, p=0.03; OR=1.34, p=0.04; respectively). The GTG haplotype was also significantly associated with RA (OR=2.27 95%CI=1.18-4.41; p=0.008), but did not show association with levels of anti-CCP antibodies and clinical parameters. In conclusion, our replication study in a Southern Mexican population suggests that PADI4 individual polymorphisms and the related susceptibility haplotype (GTG) are also genetic risk markers for RA.
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Artrite Reumatoide/genética , Marcadores Genéticos/genética , Genótipo , Desiminases de Arginina em Proteínas/genética , Adulto , Idoso , Anticorpos Antiproteína Citrulinada/sangue , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , México , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Proteína-Arginina Desiminase do Tipo 4RESUMO
INTRODUCTION: The presence of anti-CCP is an important prognostic tool of rheumatoid arthritis (RA). But research is still ongoing on its relationship with disease activity and functional capacity. OBJECTIVES: To study the relationship between anti-CCP and disease activity, functional capacity and structural damage indexes, by means of conventional radiography (CR) and magnetic resonance imaging (MRI), in cases of established RA. METHODS: Cross-sectional study with RA patients with 1-10 disease duration. Participants underwent clinical evaluation with anti-CCP. Disease activity was assessed using the Clinical Disease Activity Index (CDAI), and functional capacity through the Health Assessment Questionnaire (HAQ). CR analysis was carried out by the Sharp van der Heijde index (SvdH), and MRI analysis by RAMRIS (Rheumatoid Arthritis Magnetic Resonance Image Scoring). RESULTS: We evaluated 56 patients, with a median (IqR) age of 55 (47.5-60) years; 50 (89.3%) participants were female and 37 (66.1%) were positive for anti-CCP. Medians (IqR) of CDAI, HAQ, SvdH and RAMRIS were 14.75 (5.42-24.97) 1.06 (0.28-1.75), 2 (0-8) and 15 (7-35), respectively. There was no association between anti-CCP and CDAI, HAQ and SvdH and RAMRIS scores. CONCLUSION: Our results have not established an association of anti-CCP with the severity of disease. To date, we cannot corroborate anti-CCP as a prognostic tool in patients with established RA.
Assuntos
Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Imageamento por Ressonância Magnética , Peptídeos Cíclicos/imunologia , Artrite Reumatoide/sangue , Artrite Reumatoide/fisiopatologia , Autoanticorpos/sangue , Biomarcadores/sangue , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos Cíclicos/sangue , Valor Preditivo dos Testes , Prognóstico , Fator Reumatoide/sangue , Índice de Gravidade de DoençaRESUMO
ABSTRACT Introduction: The presence of anti-CCP is an important prognostic tool of rheumatoid arthritis (RA). But research is still ongoing on its relationship with disease activity and functional capacity. Objectives: To study the relationship between anti-CCP and disease activity, functional capacity and structural damage indexes, by means of conventional radiography (CR) and magnetic resonance imaging (MRI), in cases of established RA. Methods: Cross-sectional study with RA patients with 1–10 disease duration. Participants underwent clinical evaluation with anti-CCP. Disease activity was assessed using the Clinical Disease Activity Index (CDAI), and functional capacity through the Health Assessment Questionnaire (HAQ). CR analysis was carried out by the Sharp van der Heijde index (SvdH), and MRI analysis by RAMRIS (Rheumatoid Arthritis Magnetic Resonance Image Scoring). Results: We evaluated 56 patients, with a median (IqR) age of 55 (47.5–60) years; 50 (89.3%) participants were female and 37 (66.1%) were positive for anti-CCP. Medians (IqR) of CDAI, HAQ, SvdH and RAMRIS were 14.75 (5.42–24.97) 1.06 (0.28–1.75), 2 (0–8) and 15 (7–35), respectively. There was no association between anti-CCP and CDAI, HAQ and SvdH and RAMRIS scores. Conclusion: Our results have not established an association of anti-CCP with the severity of disease. To date, we cannot corroborate anti-CCP as a prognostic tool in patients with established RA.
RESUMO Introdução: A presença do anti-CCP constitui importante ferramenta prognóstica da artrite reumatoide (AR), mas ainda se investiga sua relação com a atividade da doença e a a capacidade funcional. Objetivos: Estudar a relação do anti-CCP com os índices de atividade da doença, de capacidade funcional e de dano estrutural, por meio de radiografia convencional (RC) e de ressonância magnética (RM), em AR estabelecida. Métodos: Estudo transversal com pacientes com AR, com um a 10 anos de doença. Os participantes foram submetidos à avaliação clínica com pesquisa do anti-CCP. A atividade de doença foi avaliada por meio do Clinical Disease Activity Index (CDAI) e a capacidade funcional por meio do Health Assessment Questionnaire (HAQ). A análise da RC foi feita pelo índice de Sharp van der Heijde (SmvH) e da RM pelo Sistema de Pontuação de Imagem por Ressonância Magnética na Artrite Reumatoide (RAMRIS, Rheumatoid Arthritis Magnetic Resonance Image Scoring). Resultados: Foram avaliados 56 pacientes, com mediana (IIq) de 55 (47,5-60,0) anos, 50 (89,3%) do sexo feminino e 37 (66,1%) anti-CCP positivos. As medianas (IIq) do CDAI, do HAQ, de SmvH e do RAMRIS foram de 14,75 (5,42-24,97), 1,06 (0,28-1,75), 2 (0-8) e 15 (7-35), respectivamente. Não houve associação do anti-CCP com o CDAI, com o HAQ e com os escores SmvH e RAMRIS. Conclusão: Nossos resultados não estabeleceram a associação do anti-CCP com a gravidade da doença. Até o momento, não podemos corroborar o anti-CCP como uma ferramenta prognóstica em AR estabelecida.
Assuntos
Humanos , Masculino , Peptídeos Cíclicos/imunologia , Artrite Reumatoide/imunologia , Artrite Reumatoide/diagnóstico por imagem , Autoanticorpos/imunologia , Imageamento por Ressonância Magnética , Peptídeos Cíclicos/sangue , Artrite Reumatoide/fisiopatologia , Artrite Reumatoide/sangue , Prognóstico , Fator Reumatoide/sangue , Autoanticorpos/sangue , Índice de Gravidade de Doença , Biomarcadores/sangue , Estudos Transversais , Valor Preditivo dos Testes , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Leprosy patients may present several osteoarticular complaints, which require further evaluation of inflammatory diseases, such as rheumatoid arthritis (RA). Therefore, an adequate clinical assessment in addition to testing for rheumatoid factors (RF) and anticyclic citrullinated peptide antibodies (anti-CCP), can be useful in order to establish the correct diagnosis. METHOD: In this study, the relation of RF and anti-CCP with rheumatological manifestations was evaluated in 97 leprosy patients from Southern Brazil. The results were compared to RA patients and healthy controls from the same geographical area and ethnic background. RESULTS: Neuropathy was observed in 71.1% and arthritis in 35.1% of the leprosy patients. A high frequency of RF positivity was observed among the leprosy patients (41.2%, 40/97), with RF immunoglobulin A (IgA) significantly associated with arthritis (OR = 7.9, 95% CI = 1.5-40.6 P = 0.008). Anti-CCP was observed in 9.3% (9/97) of the patients, with anti-CCP2 being the most frequent subtype. Only 4.1% (4/97) of the patients were RF and anti-CCP concomitantly positive. RF IgM showed a significant association with leprosy when compared to healthy controls (P < 0.0001) whereas for anti-CCP2 no significant results were observed (P = 0.0585). However, both biomarkers showed a strong association with RA when compared to leprosy in patients from the same geographical area and ethnic background (anti-CCP2 OR = 38.6; 95% CI = 16.49-90.26; P < 0.0001 and RF IgM OR = 4.51; 95% CI = 2.62-7.77; P < 0.0001). CONCLUSION: Due to the similarity of some rheumatological manifestations in leprosy with other inflammatory diseases, such as RA, clinical and laboratorial evaluation of affected patients must be carefully assessed in order to achieve proper diagnosis and treatment.
Assuntos
Artrite Reumatoide/imunologia , Imunoglobulina M/sangue , Hanseníase/imunologia , Peptídeos Cíclicos/imunologia , Fator Reumatoide/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/etnologia , Biomarcadores/sangue , Brasil/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Hanseníase/sangue , Hanseníase/diagnóstico , Hanseníase/etnologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Fatores de Risco , Adulto JovemRESUMO
INTRODUCTION: The presence of anti-CCP is an important prognostic tool of rheumatoid arthritis (RA). But research is still ongoing on its relationship with disease activity and functional capacity. OBJECTIVES: To study the relationship between anti-CCP and disease activity, functional capacity and structural damage indexes, by means of conventional radiography (CR) and magnetic resonance imaging (MRI), in cases of established RA. METHODS: Cross-sectional study with RA patients with 1-10 years of disease duration. Participants underwent clinical evaluation with anti-CCP. Disease activity was assessed using the Clinical Disease Activity Index (CDAI), and functional capacity through the Health Assessment Questionnaire (HAQ). CR analysis was carried out by the Sharp van der Heijde index (SvdH), and MRI analysis by RAMRIS (Rheumatoid Arthritis Magnetic Resonance Image Scoring). RESULTS: We evaluated 56 patients, with a median (IqR) age of 55 (47.5-60.0) years; 50 (89.3%) participants were female and 37 (66.1%) were positive for anti-CCP. Medians (IqR) of CDAI, HAQ, SvdH and RAMRIS were 14.75 (5.42-24.97) 1.06 (0.28-1.75), 2 (0-8) and 15 (7-35), respectively. There was no association between anti-CCP and CDAI, HAQ and SvdH and RAMRIS scores. CONCLUSION: Our results have not established an association of anti-CCP with the severity of disease. To date, we cannot corroborate anti-CCP as a prognostic tool in patients with established RA.
RESUMO
Peptidyl arginine deiminase IV (PADI4) enzyme catalyzes the citrullination of proteins, which are recognized by anti-cyclic citrullinated peptide antibodies (anti-CCP) in rheumatoid arthritis (RA) patients. Here, we determined the association between PADI4 gene polymorphisms and haplotypes with RA susceptibility and clinical characteristics in a western Mexican population. The relationship of PADI4 polymorphisms with anti-CCP and PADI4 mRNA expression was also evaluated. PADI4_89, PADI4_90 and PADI4_92 polymorphisms were individually associated with RA susceptibility. The GTG haplotype was significantly associated with: RA susceptibility; disease onset at ≤ 40 years and anti-CCP antibodies. PADI4 expression was three fold higher in RA patients carrying the susceptibility haplotype (GTG) than in non-susceptibility haplotype carriers (ACC). In conclusion, polymorphisms and functional haplotype (GTG) in PADI4 are associated with RA susceptibility as well as anti-CCP antibodies in a Mexican population. This supports the role of PADI4 early in RA pathogenesis by promoting the generation of citrullinated autoantigens.
Assuntos
Artrite Reumatoide/genética , Predisposição Genética para Doença/genética , Haplótipos , Hidrolases/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Feminino , Regulação Enzimológica da Expressão Gênica , Frequência do Gene , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , México , Pessoa de Meia-Idade , Peptídeos Cíclicos/imunologia , Proteína-Arginina Desiminase do Tipo 4 , Desiminases de Arginina em Proteínas , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease of unclear etiology that is manifested in by a progressive and destructive polyarthritis in association with serological evidence of autoreactivity. Its diagnosis is based on the classification criteria that involve four parameters: joint involvement, serology (rheumatoid factor and anti-cyclic citrullinated peptide--anti-CCP), levels of acute phase reactants and the duration of the symptoms Aletaha, et al. [1]. This classification simplifies the categorization of the patients with early RA; however, the diagnosis requires highly trained specialists who are able to differentiate early symptoms of RA from other pathologies.
Assuntos
Artrite Reumatoide/classificação , Artrite Reumatoide/diagnóstico , Artralgia/classificação , Artralgia/diagnóstico , Artralgia/imunologia , Artrite Reumatoide/imunologia , Biomarcadores/sangue , Doença Crônica , Comorbidade/tendências , Progressão da Doença , Diagnóstico Precoce , Humanos , Inflamação/sangue , Inflamação/classificação , Inflamação/diagnóstico , Peptídeos Cíclicos/efeitos adversos , Peptídeos Cíclicos/sangue , Peptídeos Cíclicos/imunologia , Fator Reumatoide/efeitos adversos , Fator Reumatoide/sangue , Sinovite/classificação , Sinovite/diagnóstico , Sinovite/imunologiaRESUMO
Introducción: la esclerodermia es una alteración autoinmune caracterizada por induración y engrosamiento de la piel. Durante el curso de la enfermedad los pacientes pueden padecer síntomas de afectación musculoesquelética que incluyen artralgias, artritis, pérdida de función articular y discapacidad consecuente. Objetivos: se estudió la relación de las manifestaciones osteo-articulares clínicas y radiológicas con los anticuerpos anti-péptido citrulinado en una cohorte de pacientes con esclerodermia. Materiales y métodos: se evaluó la historia clínica de pacientes con esclerodermia buscando datos con características de la enfermedad, afectación de órgano blanco y síntomas osteo-articulares. A todos los pacientes se les realizó anticuerpos anti-péptido citrulinado de tercera generación y se les tomó radiografía de manos y pies. Resultados: se incluyeron en forma consecutiva 123 pacientes y se analizaron los datos de 100 pacientes. Ochenta y cuatro pacientes con esclerodermia limitada y 16 con esclerodermia difusa. El promedio de edad fue de 55,5 años y la mediana del tiempo de diagnóstico correspondió a 6,9 años. Catorce pacientes presentaron anticuerpos anti-péptido citrulinado positivos (14%), 4 pacientes con esclerodermia difusa y 9 pacientes con esclerodermia limitada. Dieciocho pacientes (18%) presentaron el factor reumatoide IgM positivo y no se observó relación entre la afectación de órgano blanco con los anticuerpos. El 72% de los pacientes presentaron síntomas osteo-articulares, 17 de ellos presentaron artralgias (23,6%). La combinación de artralgias y artritis se observó en 25 (34,7%) de los pacientes. Artralgias, artritis y contracturas en 10 (13,9%) pacientes. Dos pacientes presentaron artritis (2,8%), 3 contracturas (4,2%) y 5 calcinosis (6,9%). Analizando la asociación entre los anticuerpos antiCCP y la afectación clínica articular, no se encontró asociación estadísticamente significativa (p= 0,095). En el análisis radiológico se observó: En las manos con mayor frecuencia resorción ósea u osteolisis (72%). También se observó calcinosis (54%), aumento de tejidos blandos (49%) y contracturas en flexión (31%). En los pies se observó con mayor frecuencia resorción falángica u osteolisis (13%). Además calcinosis (10%), disminución del espacio articular (6%). Se evidenció una asociación de calcinosis con los antiCCP positivos. Conclusión: los hallazgos articulares fueron frecuentes en esta cohorte de pacientes con esclerodermia. La prevalencia de los anticuerpos antiCCP y factor reumatoide fueron de alrededor del 15%. Se observó más alteraciones radiológicas en las manos que los pies probablemente por factores mecánicos. Se observó una asociación de calcinosis en las manos con los antiCCP.
Introduction: scleroderma is an autoimmune disease characterized by induration and thickening of skin. Patients may suffer from musculoskeletal symptoms which include arthralgias, arthritis, loss of articular function and disability. Objectives: we sought to assess any association between radiographic features, osteoarticular manifestations, and anti-CCP antibodies in a cohort of scleroderma patients. Materials and methods: we evaluated the clinical features of patients searching for demographic characteristics, organ system involvement and osteoarticular symptoms. The presence of anti-CCP IgG was evaluated in all patients. Standard radiographs of hands and feet were taken and analyzed. Results: one hundred twenty three consecutive patients were included and 100 patients were analyzed in the present study. Eighty four patients had limited scleroderma and 16 patients had diffuse scleroderma. The mean age was 55.5 years and the median time of diagnostic was 6.9 years. Fourteen patients were positive for presence of anti-CCP (14%), 4 patient for diffuse form and 9 patients for limited form. Eighteen patients were positive for IgM rheumatoid factor test (18%). It was not seen an association between organ involvement and antibodies. Seventy two percent of patients showed osteoarticular symptoms, 17 of them had arthralgias (23.6%), 25 had arthralgias and arthritis (34.7%), and 10 had arhtralgias, arthritis and contractures (13.9%). Two patients showed arthritis (2.8%), three contractures (4.2%) and 5 calcinosis (6.9%). There was no association between the presence of anti-CCP antibodies and osteoarticular manifestations (p= 0.095). Radiographic features seen on hands were osteolysis (72%), calcinosis (54%), increasing of soft tissues (49%) and flexion contractures (31%). On feet was seen osteolysis (13%), calcinosis (10%) and decreasing of articular space (6%). There was association between calcinosis and anti-CCP antibodies. Conclusion: the articular findings were frequently seen in this scleroderma cohort. Prevalence of anti-CCP antibodies and rheumatoid factor was around 15% positive. Hands showed more alterations than feet, probably for mechanistic factors. It was seen an association between hand calcinosis and anti-CCP antibodies.
Assuntos
Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antiproteína Citrulinada , Anticorpos , Pacientes , Doenças Autoimunes , ArtropatiasRESUMO
INTRODUÇÃO/OBJETIVO: Caracterizar uma população de pacientes com artrite reumatoide (AR) inicial quanto aos aspectos laboratoriais, comparando-a com outras coortes similares. PACIENTES E MÉTODOS: Os dados apresentados fazem parte de um estudo prospectivo de coorte incidente, em que foram avaliados 65 pacientes com AR inicial, acompanhados por 36 meses a partir do diagnóstico, na Clínica de Artrite Reumatoide Inicial do Hospital Universitário de Brasília (HUB). Foram registrados os dados demográficos, clínicos e laboratoriais pertinentes à avaliação inicial da coorte, incluindo hematimetria, provas de atividade inflamatória e presença de autoanticorpos (fator reumatoide - FR, anticorpos antipeptídeos citrulinados cíclicos - anti-CCP e antivimentina citrulinada - anti-Sa). RESULTADOS: Houve predomínio de mulheres (86 por cento), com média de idade de 45,6 anos. Doze pacientes (18,46 por cento) tiveram o diagnóstico laboratorial de anemia (hemoglobina < 12 g/dL). Velocidade de hemossedimentação (VHS) e proteína C reativa (PCR) encontravam-se acima do valor de referência em 51 (78,46 por cento) e 46 (70,76 por cento) pacientes, respectivamente. Trinta e dois indivíduos (49,23 por cento) foram positivos para pelo menos um dos isotipos de FR, sendo que 28 pacientes (43,07 por cento) foram positivos para FR IgA, 19 (29,23 por cento) para FR IgG e 32 (49,23 por cento) para FR IgM, respectivamente; 34 pacientes (52,30 por cento do total) foram positivos para pelo menos uma das técnicas utilizadas na averiguação de anti-CCP (CCP2, CCP3 ou CCP3.1), enquanto 9 (13,85 por cento) o foram para anti-Sa. CONCLUSÕES: As características laboratoriais dos pacientes acompanhados nessa coorte brasileira se assemelham em vários aspectos a coortes norte-americanas, europeias e latino-americanas anteriormente publicadas.
INTRODUCTION/OBJECTIVE: To characterize a population of patients with early rheumatoid arthritis (RA) according to laboratory aspects, comparing it with other similar cohorts. METHODS: Data presented are part of a prospective incident cohort study that evaluated 65 patients with early RA, followed for 36 months from the diagnosis at Early Rheumatoid Arthritis Clinic of Hospital Universitário de Brasília (HUB). We recorded demographics, clinical, and laboratory data relevant to the cohort initial assessment, including red blood cells, evidence of inflammatory activity, and presence of autoantibodies (rheumatoid factor (RF)), cyclic citrullinated peptide antibodies (anti-CCP), and antivimentin citrullinated (anti-Sa). RESULTS: There was a preponderance of female (86 percent) with mean age of 45.6 years. Twelve patients (18.46 percent) had laboratory diagnosis of anemia (hemoglobin < 12 g / dL). Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were above the reference value for 51 (78.46 percent) and 46 (70.76 percent) patients, respectively. Thirty-two patients (49.23 percent) were positive for at least one of the RF isotypes, and 28 patients (43.07 percent) were positive for IgA RF, 19 (29.23 percent) for IgG, and 32 ( 49.23 percent) for IgM RF, respectively; 34 patients (52.30 percent) were positive for at least one of the techniques used in investigation of anti-CCP (CCP2, or CCP3, or CCP3.1), while 9 (13,85 percent) were positive for anti-Sa. CONCLUSIONS: The laboratory characteristics of patients enrolled in this Brazilian cohort are similar in many respects to those of North-American, European, and Latin-American cohorts previously published.