RESUMO
Determination of anti-citrullinated peptide antibodies (ACPA) plays a relevant role in the diagnosis of rheumatoid arthritis (RA). To date, it is still unclear if the use of several tests for these autoantibodies in the same patient offers additional value as compared to performing only one test. Therefore, we evaluated the performance of using two assays for ACPA: second-generation anti-citrullinated cyclic peptides antibodies (anti-CCP2) and anti-mutated citrullinated vimentin (anti-MCV) antibodies for the diagnosis of RA. We compared three groups: RA (n = 142), chronic inflammatory disease (CIRD, n = 86), and clinically healthy subjects (CHS, n = 56) to evaluate sensitivity, specificity, predictive values, and likelihood ratios (LR) of these two assays for the presence of RA. A lower frequency of positivity for anti-CCP2 was found in RA (66.2%) as compared with anti-MCV (81.0%). When comparing RA versus other CIRD, sensitivity increased when both assays were performed. This strategy of testing both assays had high specificity and LR+. We conclude that adding the assay of anti-MCV antibodies to the determination of anti-CCP2 increases the sensitivity for detecting seropositive RA. Therefore, we propose the use of both assays in the initial screening of RA in longitudinal studies, including early onset of undifferentiated arthritis.
Assuntos
Anticorpos/isolamento & purificação , Artrite Reumatoide/diagnóstico , Febre Reumática/diagnóstico , Vimentina/imunologia , Adulto , Anticorpos/sangue , Anticorpos/imunologia , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Citrulina/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos Cíclicos/sangue , Peptídeos Cíclicos/imunologia , Febre Reumática/imunologia , Febre Reumática/patologiaRESUMO
Posttranslational modifications (PTMs) are defined as covalent modifications occurring in a specific protein amino acid in a time- and signal-dependent manner. Under physiological conditions, proteins are posttranslationally modified to carry out a large number of cellular events from cell signaling to DNA replication. However, an absence, deficiency, or excess in PTMs of a given protein can evolve into a target to trigger autoimmunity, since PTMs arise in the periphery and may not occur in the thymus; hence, proteins with PTMs never tolerize developing thymocytes. Consequently, when PTMs arise during cellular responses, such as inflammation, these modified self-antigens can be taken up and processed by the antigen-presenting cells (APCs). Autoreactive T cells, which recognize peptides presented by APCs, can then infiltrate into host tissue where the modified antigen serves to amplify the autoimmune response, eventually leading to autoimmune pathology. Furthermore, a PTM occurring in an amino acid residue can induce changes in the net charge of the protein, leading to conformational modifications in the tertiary and quaternary structure of the protein, especially interaction with human leukocyte antigen (HLA) molecules. Molecular mimicry (MM) was until now the prevailing hypothesis explaining generation of autoimmunity; nevertheless, experimental animal models need inflammation via infection or other immunogens to ensure autoimmunity; MM alone is not sufficient to develop autoimmunity. PTMs could arise as an additive factor to MM, which is required to start an autoimmune response. PTMs have been found to be present in different pathologic conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), antiphospholipid syndrome, and primary biliary cirrhosis. The aim of the present review is to expose protein posttranslational modifications and the evidence suggesting their role in the generation of autoimmunity.
Assuntos
Autoantígenos/metabolismo , Doenças Autoimunes/imunologia , Autoimunidade , Processamento de Proteína Pós-Traducional , Animais , Apresentação de Antígeno , Autoantígenos/imunologia , Modelos Animais de Doenças , Antígenos HLA/metabolismo , Humanos , Conformação MolecularRESUMO
We evaluated the association between anti-cyclic citrullinated peptide antibodies (anti-CCP) and anti-mutated citrullinated vimentin antibodies (anti-MCV) with the presence of extra-articular (ExRA) manifestations in 225 patients with rheumatoid arthritis (RA). Ninety-five patients had ExRA and 130 had no ExRA. There was no association of anti-CCP and anti-MCV levels with the presence of ExRA as total group (P = 0.40 and P = 0.91, resp.). Making an analysis of individual manifestations, rheumatoid nodules were associated with positivity for rheumatoid factor (RF); (P = 0.01), anti-CCP (P = 0.048), and anti-MCV (P = 0.02). Instead, RF, anti-CCP, or anti-MCV were not associated with SS, chronic anemia, or peripheral neuropathy. Levels of anti-CCP correlated with the score of the Health Assessment Questionnaire-Disability Index (HAQ-Di) (r = 0.154, P = 0.03), erythrocyte sedimentation rate (ESR); (r = 0.155, P = 0.03), and RF (P = 0.254, P < 0.001), whereas anti-MCV titres only correlated with RF (r = 0.169, P = 0.02). On adjusted analysis, ExRA was associated with longer age (P = 0.015), longer disease duration (P = 0.007), higher DAS-28 score (P = 0.002), and higher HAQ-DI score (P = 0.007), but serum levels of anti-CCP and anti-MCV were not associated. These findings show the need to strengthen the evaluation of the pathogenic mechanisms implied in each specific ExRA manifestation.
Assuntos
Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Peptídeos Cíclicos/imunologia , Vimentina/imunologia , Adulto , Idoso , Artrite Reumatoide/complicações , Autoanticorpos/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
The use of biomarkers as tools to evaluate genotoxicity is increasing recently. Methods that have been used previously to evaluate genomic instability are frequently expensive, complicated, and invasive. The micronuclei (MN) and nuclear abnormalities (NA) technique in buccal cells offers a great opportunity to evaluate in a clear and precise way the appearance of genetic damage whether it is present as a consequence of occupational or environmental risk. This technique is reliable, fast, relatively simple, cheap, and minimally invasive and causes no pain. So, it is well accepted by patients; it can also be used to assess the genotoxic effect derived from drug use or as a result of having a chronic disease. Furthermore the beneficial effects derived from changes in life style or taking additional supplements can also be evaluated. In the present paper, we aim to focus on the explanation of MN test and its usefulness as a biomarker; we further give details about procedures to perform and interpret the results of the test and review some factors that could have an influence on the results of the technique.
Assuntos
Dano ao DNA , Micronúcleos com Defeito Cromossômico , Mucosa Bucal/patologia , Animais , Biomarcadores , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/patologia , Núcleo Celular/efeitos da radiação , Citodiagnóstico , Humanos , Testes para MicronúcleosRESUMO
Peptidyl arginine deiminase IV (PAD 4) is the responsible enzyme for a posttranslational modification called citrullination, originating the antigenic determinant recognized by anti-cyclic citrullinated peptide antibodies (ACPA). Four SNPs (single nucleotide polymorphisms) have been described in PADI4 gene to form a susceptibility haplotype for rheumatoid arthritis (RA); nevertheless, results in association studies appear contradictory in different populations. The aim of the study was to analyze if the presence of three SNPs in PADI4 gene susceptibility haplotype (GTG) is associated with ACPA positivity in patients with RA. This was a cross-sectional study that included 86 RA patients and 98 healthy controls. Polymorphisms PADI4_89, PADI4_90, and PADI4_92 in the PADI4 gene were genotyped. The susceptibility haplotype (GTG) was more frequent in RA patients; interestingly, we found a new haplotype associated with RA with a higher frequency (GTC). There were no associations between polymorphisms and high scores in Spanish HAQ-DI and DAS-28, but we did find an association between RARBIS index and PADI4_89, PADI4_90 polymorphisms. We could not confirm an association between susceptibility haplotype presence and ACPA positivity. Further evidence about proteomic expression of this gene will determine its participation in antigenic generation and autoimmunity.
Assuntos
Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Predisposição Genética para Doença , Haplótipos , Hidrolases/genética , Adulto , Alelos , Artrite Reumatoide/tratamento farmacológico , Autoanticorpos/sangue , Autoanticorpos/imunologia , Estudos de Casos e Controles , Estudos Transversais , Frequência do Gene , Genótipo , Humanos , México , Pessoa de Meia-Idade , Peptídeos Cíclicos/imunologia , Polimorfismo de Nucleotídeo Único , Proteína-Arginina Desiminase do Tipo 4 , Desiminases de Arginina em Proteínas , Fatores de RiscoRESUMO
Leprosy offers a broad spectrum of altered immunological sceneries, ranging from strong cell-mediated immune responses seen in tuberculoid leprosy (TT), through borderline leprosy (BB), to the virtual absence of T cell responses characteristic in lepromatous leprosy (LL). The exact mechanism of autoantibodies production remains unknown in leprosy and other chronic inflammatory diseases and also the contribution of these antibodies to the pathogenesis of the disease. The aim of this study is to evaluate the frequency and profiles of serum anti-cyclic citrullinated peptide antibodies (a-CCP), rheumatoid factor (RF) and its relationship with leprosy spectrum. Serum samples from 67 leprosy patients (54 LL, 5 TT and 8 BB) and 46 clinically healthy subjects (CHS) from the same endemic region were investigated. The clinical chart and questionnaire were used to obtain clinical information. Anti-cyclic citrullinated peptide antibodies (a-CCP) were measured by enzyme-linked immunosorbent assay, whereas the rheumatoid factor (RF) levels were measured by nephelometric method. The mean age of patients was 51.5 ± 13 years. Sera levels of a-CCP where higher in leprosy patients than in CHS (5.9 ± 11.6 vs. 0.3 ± 0.29) (P < 0.0001); the same pattern was found for RF sera titers without reaching statistical significance (16.8 ± 22.5 vs. 9.9 ± 3) (P = NS). We did not find a correlation between a-CCP and RF Rho =0.02786 (IC 95%) P = 0.8229. However, LL patients had higher a-CCP and RF levels than TT patients. Although an absence in correlation was observed, the serum levels of a-CCP antibodies and RF appeared to be useful in distinguishing LL from TT patients with a limited significance in detecting reactional leprosy patients.
Assuntos
Artrite Reumatoide/diagnóstico , Autoanticorpos/sangue , Hanseníase/imunologia , Peptídeos Cíclicos/imunologia , Fator Reumatoide/sangue , Adulto , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Estudos Transversais , Feminino , Humanos , Hanseníase/sangue , Masculino , México , Pessoa de Meia-Idade , Estudos Retrospectivos , Fator Reumatoide/imunologiaRESUMO
BACKGROUND: The prevalence of vertebral fractures in systemic lupus erythematosus (SLE) ranges between 20% and 21.4%, and patients with these fractures have impaired walking and activities of daily living. Moreover, clinical and radiological vertebral fractures have been associated with increased mortality. OBJECTIVES: To compare the quality of life of patients with SLE with and without vertebral fractures. METHODS: The study group comprised 140 women with SLE undergoing screening for vertebral fractures using a standardized method. SLE disease activity and organ damage were measured by the Mexican Systemic Lupus Erythematosus Disease Activity Index (MEX-SLEDAI) and the Systemic International Collaborating Clinics/American College of Rheumatology damage index (SLICC), respectively. The QUALEFFO and Center for Epidemiologic Studies Depression Scale were used to measure health-related quality of life and depression, respectively. RESULTS: The median age of the 140 patients was 43 years (range 18-76); disease duration was 72 months (range 6-432); 49.7% were menopausal. Thirty-four patients (24.8%) had vertebral fractures (> or = 1), mostly in the thoracic spine. Patients with vertebral fractures had a higher mean age (49.5 +/- 13.4 vs. 41 - 13.2 years, P= 0.001) and disease damage (57.1% vs. 34.4%, P = 0.001). The global QUALEFFO score was not different between the vertebral fractures group and the non-vertebral group. The only significant difference in the QUALEFFO items was in physical function (P = 0.04). A significant correlation was found between the severity of vertebral fractures and the QUALEFFO pain (r = 0.27, P = 0.001) and physical function (r = 0.37, P = 0.02) scores. The number of vertebral fractures correlated only with physical function (r = 0.01). CONCLUSIONS: The HRQOL of women with SLE is low, regardless of whether they have vertebral fractures or not, but patients with vertebral fractures have worse physical function compared to those without. Strategies to improve the HRQOL of patients with SLE with or without vertebral fractures are necessary.
Assuntos
Vértebras Lombares/lesões , Lúpus Eritematoso Sistêmico/psicologia , Qualidade de Vida , Fraturas da Coluna Vertebral/psicologia , Vértebras Torácicas/lesões , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Vértebras Lombares/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/complicações , México/epidemiologia , Pessoa de Meia-Idade , Prevalência , Radiografia , Estudos Retrospectivos , Fatores de Risco , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Taxa de Sobrevida/tendências , Vértebras Torácicas/diagnóstico por imagem , Adulto JovemRESUMO
OBJECTIVE: To describe the clinical aspects, treatment and evolution of acute abdomen caused by torsion of the greater omentum. METHODS: Retrospective analysis study consisted of a group of eleven patients with acute abdomen caused by torsion of the greater omentum. The variables included were age, sex, body mass index (BMI), clinical picture, evolution time, laboratory tests, radiology and treatment. Descriptive statistical analysis was employed. RESULTS: Seven (63.6%) women and four (36.36%) men; mean age 33 (20 to 58) years; BMI > 25.0 in nine (81.81%); average evolution 6.54, SD 3.47 days. All presented abdominal pain, six (54.5%) abdominal distension, four (36.3%) walking difficulty, three (27.27%) general malaise, ten (90.9%) slight leucocytosis, five (45.4%) previous surgery. In all cases diagnosis was made by laparotomy, treatment was resection of the affected segment, and no complications were seen. CONCLUSIONS: Segmental torsion of the greater omentum is a rare cause of acute abdomen. Pain is the most frequent symptom, and the condition resembles acute appendicitis. It is often discovered during surgery and is treated by the removal of the affected omentum segment.
Assuntos
Abdome Agudo/etiologia , Omento , Doenças Peritoneais/complicações , Anormalidade Torcional/complicações , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Latex allergy is the second cause of perioperative anaphylaxis. Anesthesiologists play a key role in opportune identification of risk factors, as well as clinical diagnosis and therapeutic management. OBJECTIVE: To evaluate the anesthesiologists aptitude to identify and treat latex allergy. PARTICIPANTS AND METHODS: Sixty-six anesthesiologists from five general hospitals located at Guadalajara, Jalisco, Mexico, were evaluated. Aptitude was determined by applying a validated structured instrument. Aptitude levels were measured by using an ordinal scale. Comparisons were performed using Mann Whitney U test. RESULTS: Anesthesiologist's global aptitude ranged from -2 to 27 with a median of 8 (from a maximum value in the scale of 40); frequencies by each category of the scale were: Random 48 (72.7%), Very bad 11 (16.7%), Bad 4 (6.1%) and Medium only 3 (4.5%). Both Good and Very good categories registered no anesthesiologist. The relationship of this indicator with other variables did not reach statistical significance (KW 6.478; p = 0.16617). CONCLUSIONS: A suboptimal aptitude was identified among anesthesiologists regarding identification of latex allergy. A need to establish new strategies for educative intervention in order to improve this issue was identified.
Assuntos
Anestesiologia , Aptidão , Competência Clínica/estatística & dados numéricos , Hipersensibilidade ao Látex/diagnóstico , Assistência Perioperatória , Médicos/psicologia , Anafilaxia/diagnóstico , Anafilaxia/etiologia , Anafilaxia/prevenção & controle , Anafilaxia/terapia , Anestesiologia/educação , Anestesiologia/estatística & dados numéricos , Educação Médica Continuada , Hospitais Gerais , Humanos , Complicações Intraoperatórias/diagnóstico , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/prevenção & controle , Complicações Intraoperatórias/terapia , Hipersensibilidade ao Látex/complicações , Hipersensibilidade ao Látex/epidemiologia , Hipersensibilidade ao Látex/terapia , México/epidemiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/terapia , Fatores de RiscoRESUMO
OBJECTIVE: To evaluate sera titers for antibodies anti-cyclic citrullinated peptide and their correlation against sera levels of anti-topoisomerase I and anti-centromere antibodies in Mexican patients with systemic sclerosis. PATIENTS AND METHODS: Consecutive outpatients with systemic sclerosis who attending to rheumatology clinic at a second level hospital facility. The antibodies anti-cyclic citrullinated peptide, anti-topoisomerase I and anti-centromere were determined by enzymatic immunoassay (ELISA). STATISTICAL ANALYSIS: Spearman for correlation between numerical variables with nonparametric distribution. Fisher exact test or chi2 to compare proportions and Student t test for dimensional variables. RESULTS: Thirty female patients were included; aged 53 +/- 13, the disease duration at the time of the study was 10 +/- 9. Twenty-three patients (77%) exhibited diffuse disease. Anti-centromere, anti-topoisomerase I, and anti-cyclic citrullinated peptide were detected in nine, nine and three patients respectively. The correlation analysis showed the independence of autoantibodies anti-centromere and anti-topoisomerase I with respect to the levels of anti-cyclic citrullinated peptide. CONCLUSIONS: This study confirms the low frequency of anti-cyclic citrullinated peptide antibodies in patients with systemic sclerosis. A lack of correlation between autoantibodies considered as "mutually excluded" anti-topoisomerase I and anti-centromere, indicating that the analysis of the relevance for anti-cyclic citrullinated peptide in systemic sclerosis must include other clinical and serological variables.