Shared epitope classification methods according to Gregersen and de Vries allow adequate characterization of patients with rheumatoid arthritis in a Colombian population

Introduction: The most important genetic association in rheumatoid arthritis (RA) is presented with some alleles from the HLA-DRB1 gene that encode the shared epitope (SE). Objectives: To apply the SE classification methods of Gregersen, de Vries, Raychaudhuri, Mattey, and Tezenas du Montcel in a group of Colombian patients with RA and determine the most common HLA-DRB1 alleles in the population. Methods: RA diagnosis, genetic study of the HLA-DRB1 region using Luminex technology in 50 RA and 50 healthy subjects. For the classification analysis, Fisher's exact test and chi-squared test were applied. Tables were created to count the RA-related alleles. We used odds ratio to determine the risk between the presence of the shared epitope (SE) and anti-cyclic citrullinated peptides (Anti-CCP). Results: Gregersen and de Vries methods were suitable for the characterization of RA in this population (p = .006). The most prevalent HLA-DRB1 alleles in the RA group were 14:02,04:04, 08:02,04:05, and 10:01. High frequencies of the 07:01, 03:01,13:02,01:02, and 12:01 HLA-DRB1 alleles were found in the healthy population. HLA-DRB1 alleles with similar distribution in both populations were 04:07, 15:01, 11:01, 16:02, and 01:01. A high frequency of SE + was observed in Anti-CCP + individuals (63.15%); however, this was not statistically significant [OR2.4 (.63-9.01); p = .19]. Conclusion: The SE classification methods of Gregersen and de Vries were adequate in characterizing RA in a Colombian population group. An equivalence of 100% was verified between the susceptibility alleles defined by de Vries and the alleles assigned as SE according to Gregersen.

Introducción: La asociación genética más importante en artritis reumatoide (AR) se presenta con algunos alelos del gen HLA DRB1 que codifican el epítope compartido (EC). Objetivos: Aplicar los métodos de clasificación de EC de Gregersen et al., de Vries et al., Raychaudhuri et al., Mattey et al., y Tezenas du Montcel et al., en un grupo de pacientes colombianos con AR, y determinar los alelos HLA DRB1 más frecuentes en esta población. Métodos: Diagnóstico para AR, estudio genético de la región HLA DRB1 por tecnología Luminex® de 50 sujetos AR y 50 sanos. Para análisis comparativos de clasificaciones EC, se aplicaron las pruebas test exacto de Fisher y Chi-cuadrado y se realizaron tablas de conteos para los alelos relacionados con AR. Se estimó la razón de odds para determinar el riesgo entre la presencia de EC y los anticuerpos antipéptidos cíclicos citrulinados (anti-PCC). Resultados: Los métodos de Gregersen et al. y de Vries et al. fueron adecuados para la caracterización de AR en esta población (p = 0,006). Los alelos HLA DRB1 más prevalentes en el grupo AR fueron 14:02, 04:04, 08:02, 04:05 y 10:01. Se encontraron altas frecuencias de los alelos HLA DRB1 07:01, 03:01,13:02, 01:02 y 12:01 en población sana. Alelos HLA DRB1 con distribución similar en ambas poblaciones fueron: 04:07, 15:01, 11:01, 16:02 y 01:01. Se observó alta frecuencia de individuos EC+ en el grupo AR anti-PCC+ (63,15%); no obstante, sin asociación estadística (OR: 2,4 [0,63-9,01]; p = 0,19). Conclusión: Los métodos de clasificación para EC de Gregersen et al. y de Vries et al. fueron adecuados caracterizando AR en un grupo de población colombiana. Se corroboró equivalencia del 100% entre los alelos de susceptibilidad definidos por de Vries y los alelos asignados como EC según Gregersen et al.

Manifestações oculares da artrite reumatoide e positividade de autoanticorpos: uma revisão sistemática / Ocular manifestations of rheumatoid arthritis and autoantibodies positivity: a systematic review

Contexto: As manifestações oculares da artrite reumatoide representam cerca de 40% das manifestações extra-articulares, acarretando comprometimento da qualidade de vida. O fator reumatoide e o anticorpo contra peptídeos citrulinados cíclicos são marcadores sorológicos para diagnóstico laboratorial da doença. Objetivo: Identificar as principais manifestações oculares da artrite reumatoide e a sua relação com a positividade do fator reumatoide e anticorpo contra peptideos citrulinados cíclicos, através de uma revisão sistemática. Métodos: Uma revisão sistemática foi conduzida nas bases de dados: PubMed, Scopus, Web of Science e SciELO, até janeiro de 2018. Critérios de inclusão e exclusão foram aplicados e dados dos estudos selecionados foram extraídos e organizados em tabelas e gráficos. Avaliação metodológica e análise estatística, incluindo duas meta-análises, foram realizadas. Os estudos selecionados foram armazenados no Software Endnote X8 versão student (Serial Number: 3151802521 e Product Key: L899B-8N8FJ-SX9JW-BEQ58-U9HCD). Análises estatísticas foram realizadas com o Software Review Manager versão 5.3 (software gratuito). Resultados: Dos 1.985 estudos encontrados através da busca em bases de dados, quatro estudos foram incluídos. A síndrome sicca e síndrome de Sjögren secundária representaram cerca de 50% das manifestações oculares. Meta-análises aplicadas em dois estudos não identificaram associação de risco estatisticamente significativa entre o anticorpo contra peptideos citrulinados cíclicos e fator reumatoide e o desenvolvimento de manifestações oculares. Conclusão: As manifestações oculares da Artrite Reumatoide correspondem à significativa parcela das manifestações extra-articulares. No entanto, não foram constatadas associação de risco entre autoanticorpos e tais manifestações. [au]

Background: Ocular involvement represents about 40% of extra-articular manifestations of Rheumatoid Arthritis, pointing to impairment in patients' quality of life. Anti-cyclic citrullinated peptide antibody and rheumatoid factor are serological markers to laboratorial diagnosis of disease. Objective: Identify main ocular manifestations of Rheumatoid Arthritis and its relationship between positivity of rheumatoid factor and anti-cyclic citrullinated peptide antibody, through a Systematic Review of literature. Methods: Systematic Review was conducted on database search, including: PubMed, Scopus, Web of Science and SciELO until January, 2018. Inclusion and exclusion criteria were applied and data of select studies were extracted and organized in tables and graphics. Methodological appraisal and statistical analysis, including meta-analyses, were performed. Selected studies were stored in software Endnote X8 student (Serial Number: 3151802521 e Product Key: L899B-8N8FJ-SX9JW-BEQ58-U9HCD). Statistical analyses were performed with Review Manager software version 5.3 (free software). Results: From 1,985 studies found by database search, four studies were selected and analyzed. Sicca syndrome and secondary Sjögren's syndrome represented about 50% of ocular manifestations. Meta-analyses applied in two studies demonstrated no statistical significative risk association between anti-cyclic citrullinated peptide and development of ocular manifestations. Conclusion: From extra-articular manifestations of Rheumatoid Arthritis, ocular manifestations correspond to a significative amount. Nevertheless, there were no statistical significative risk association between autoantibodies and these manifestations. [au]

Effect of hot spring bathing on rheumatoid related indicators and joint pain / 上海预防医学

Objective To observe the intervention effect of typical hot spring bathing in Guizhou province on joint pain, serum anti-keratin antibody(AKA), anti-perinuclear factor antibody(APF)and anti-cyclic citrullinated peptide antibody(CCP). Methods A total of 160 people with joint pain symptoms from five typical hot spring areas in Guizhou province were selected as the subjects. They were treated with hot spring bathing intervention for 4 weeks, once a day, 5 times a week, 40 to 50 minutes each time. According to the evaluation index of physiotherapy natural mineral water in the Code for Geological Exploration and Evaluation of Natural Warm Mineral Water Resources(GB/T 13727-2016)and geological types, the five typical hot springs were divided into three different types, namely water temperature type hot springs(water temperature > 36 ℃), metasilicate type hot springs(metasilicate > 50 mg/L)and warm mineral spring type hot springs(total dissolved solids > 1 000 mg/L). WHO pain grading standard was used to score the degree of joint pain before and after hot spring bathing intervention. Serum APF, AKA and CCP antibodies were detected by ELISA kit before and after hot spring bathing. Results The joint pain score of the subjects was 2.60±0.60, and the joint pain score of the total population decreased after intervention(0.61±0.57, P < 0.05). Before intervention, the joint pain scores of water temperature type, metasilicic acid type and warm mineral spring type were 2.78±0.96, 1.98±1.15 and 3.31±0.57, respectively. After intervention, the scores of joint pain of the three kinds of hot spring bathing patients all decreased(P < 0.05), and were 0.50±0.65, 0.48±0.74 and 0.85±0.90, respectively. Before intervention, AKA(ng/L)and CCP(μg/mL)antibody levels of the observed subjects were 34.89±16.06 and 107.58±10.40, respectively, which significantly decreased after intervention(both P < 0.05), namely 26.06±10.68 and 102.93±6.01, respectively. AKA(ng/L)was 35.04±20.01 before intervention, but decreased significantly after intervention(26.61±7.54, P < 0.05). AKA(ng/L)and CCP(μg/mL)were 31.09±17.26 and 106.51±10.13 before intervention, respectively. After intervention, the above two antibody indexes significantly decreased(all P < 0.05)to 24.53±13.98 and 98.57±5.68, respectively. Before intervention, the AKA(ng/L), APF(ng/mL)and CCP(μg/mL)antibody levels were 38.40±8.66, 349.46±118.43 and 104.96±9.66, respectively. After intervention, the above three antibody indexes significantly decreased(all P < 0.05). The values were 34.00±7.55, 269.38±127.55 and 101.65±3.04, respectively. Conclusion The typical hot spring bathing intervention in Guizhou province can relieve the symptoms of joint pain, and the three types of hot springs can reduce the levels of AKA, APF and CCP antibodies to different degrees, and the warm mineral spring type of hot spring is better than the other types of hot spring.

Population distribution and clinical characteristics in rheumatoid arthritis patients with cervical spine instability / 北京大学学报(医学版)

OBJECTIVE@#To investigate the population distribution of cervical spine instability in rheumatoid arthritis (RA) patients, and to analyze the clinical characteristics in RA patients with cervical spine instability.@*METHODS@#A total of 439 RA patients who had completed cervical spine X-ray examination from Department of Rheumatology and Immunology of Peking University Shenzhen Hospital and Peking University Third Hospital from August 2015 to March 2019 were enrolled. The clinical data, laboratory data and cervical radiographic data were collected and analyzed by t-test, rank sum test and Chi-square test to clarify the clinical characteristics in the RA patients with cervical spine instability.@*RESULTS@#Of the 439 RA patients, 80.9% (355/439) were female, with an average age of (52.9±13.9) years, a median duration of the disease was 60 months, the shortest history was 2 weeks, and the longest history was up to 46 years. 29.6% (130/439) of the RA patients showed cervical spine instability. Among them, 20 RA patients were complicated with two different types of cervical instability, the atlantoaxial subluxation (AAS) accounted for 24.6% (108/439), the vertical subluxation (VS) accounted for 7.3% (32/439) and the subluxial subluxations (SAS) accounted for 2.3% (10/439). The patients with cervical spine instability had a longer duration of disease [120 (36, 240) months vs. 48 (12, 120) months], a higher proportion of peripheral joint deformity (56.9% vs. 29.9%), and a higher visual analog scale (VAS) measuring general health score (4.89±2.49 vs. 3.93±2.38), a lower hemoglobin [(111.31±19.44) g/L vs. (115.56±16.60) g/L] and a higher positive rate of anti-cyclic citrullina-ted peptide (CCP) antibody (90.8% vs. 76.6%). There were no significant differences in gender, age, number of swollen joints, number of tenderness joints, erythrocyte sedimentation rate, rheumatoid factor level, 28-joint disease activity score, positive rate of anti keratin antibody, duration of glucocorticoid use and duration of disease modifying anti-rheumatic drugs use between the two groups.@*CONCLUSION@#In the study, 29.6% of the RA patients showed cervical spine instability. RA patients with cervical spine instability had a long-term disease, a higher proportion of peripheral joint deformity, a higher VAS measuring general health score, a lower hemoglobin and a higher positive rate of anti-CCP antibody.

Clinical and laboratory characteristics of rheumatoid arthritis with positive antinuclear antibody / 北京大学学报(医学版)

OBJECTIVE@#To analyse the clinical and laboratory characteristics of antinuclear antibody (ANA) positive rheumatoid arthritis (RA) patients.@*METHODS@#The clinical and laboratory data of 428 RA cases from Department of of Rheumatology and Immunology Peking University Third Hospital from Jan 2013 to Dec 2018 were collected and used to analyse characters between ANA positive group and ANA negative group. T test was used for the quantitative data in accordance with normal distribution. Wilcoxon rank sum test was used for the quantitative data of non normal distribution. The qualitative data were analyzed by chi square test. But while 1≤theoretical frequency < 5, chi square test of corrected four grid table was used. And Fisher exact probability method was used when theoretical frequency < 1.@*RESULTS@#The number of ANA positive group was 231 (54%). The female rate was obviously higher in ANA positive group (82.7% vs. 63.5%, χ2=20.355, P < 0.01). The rate of metatarsophalangeal joints (MTPJs) involvement was lower in ANA positive group (22.1%) than in ANA negative group (33.0) (χ2=6.414, P < 0.05). The incidence of secondary Sjögren's syndrome (sSS) was much higher in ANA positive group(19.5% vs. 4.1%, χ2=23.300, P < 0.01). The positivity of rheumatoid factor (RF), as well as the positivity of anti-cyclic citrullinated peptide(CCP) antibody was much higher in ANA positive group (77.1% vs. 53.8%, χ2=25.743, P < 0.01, 74.9% vs. 59.4%, χ2=11.694, P < 0.01, respectively). The levels of immunoglobulin G (IgG) and immunoglobulin M (IgM) of ANA positive group were higher [(15.1±5.1) g/L vs. (13.8±5.3) g/L, t=2.359, P < 0.05, 1.25 (0.92) g/L vs. 1.05 (0.65) g/L, Z=-3.449, P < 0.01, respectively]. But the levels of hemoglobin (Hb) and platelet (PLT) was lower in ANA positive group[(109.64±17.98) vs. (114.47±18.48) g/L, t=-2.734, P < 0.01; (266.4×109±104.6×109) vs. (295.9×109±100.1×109) /L, t=-2.970, P < 0.01, respectively].@*CONCLUSION@#The incidence of sSS was obviously higher in ANA positive group than in ANA negative group. Serum IgG of ANA positive group was higher, but Hb and PLT were lower.

A Study of Ophthalmological Manifestations of Rheumatoid Arthritis in Eastern India

Introduction: Patients with rheumatoid arthritis (RA) who are positive for anti-cyclic citrullinated peptide (CCP)/rheumatoidfactor (RF) have more extra-articular manifestations.Purpose: We tried to evaluate the magnitude of ocular manifestations in RA patients and to find out whether there is anycorrelation of anti-CCP or RF or disease duration to ocular involvement.Materials and Methods: A total of 288 patients diagnosed as RA with ocular symptoms were evaluated. Drug-induced effectsand cataract were excluded from the study.Results: About 18.1% were male and 81.9% were female. The minimum age was 21 and the maximum was 80 years. Theaverage age was 45.66 years. About 36.8% of patients had ocular manifestations. They were bilateral in 66% of patients.Multiple ocular manifestations were shown in 60.4% of patients. Dry eye was observed in 30.5%, anterior uveitis in 6.25%, andepiscleritis and scleritis in 7.6% each. Anti-CCP was present in 86.8% and RF in 78.5% of patients. The duration of diseasewas found to be statistically significant with respect to the presentation of ocular manifestations. Anti-CCP was found to bestatistically significant with respect to ocular manifestations but statistically insignificant in case of RF. No statistical significancewas found between gender and ocular manifestations.Conclusion: So far, no published Indian study with such large number of patients looked at ocular manifestations of RA correlatingwith disease duration and impact of both anti-CCP and RF at the same time. Our study indicates that patients suffering fromRA with anti-CCP positivity and long duration of disease should be evaluated ophthalmologically.

Study on Efficacy Enhancing Effects of Compatibility of Aconitum carmichaeli Liposoluble Alkaloids and Total Glucosides of Peony in the Treatment of Wind-Cold-Dampness Type Bi-Syndrome Model Rats / 中国药房

OBJECTIVE： To study the efficacy enhancing effect of compatibility of Aconitum carmichaeli liposoluble alkaloids and total glucosides of peony in the treatment of wind-cold-dampness type bi-syndrome model rats. METHODS： Totally 100 SD male rats were randomly divided into blank group （water）， model group （water）， rotundine group [positive control， 10.0    mg/（kg·d）]， dexamethasone group [positive control， 0.3 mg/（kg·d）]，A. carmichaeli alkaloids low-dose and high-dose groups [A. carmichaeli  liposoluble alkaloid extract 12.5， 25.0 mg/（kg·d）]， total glucosides of peony low-dose and high-dose groups [total glucosides of peony powder 200.0，400.0 mg/（kg·d）]， compatibility low-dose and high-dose groups [A. carmichaeli  liposoluble alkaloid+total glucosides of peony powder were 12.5 mg/（kg·d）+400.0 mg/（kg·d）， 25.0 mg/（kg·d）+800.0 mg/（kg·d） respectively]， with 10 rats in each group. Except for blank group， other groups were given complete Freund’s adjuvant 0.1 mL on the right hind paw and wind-cold-dampness stimulation to induce wind-cold-dampness type bi-syndrome model. Nineteen days after modeling， they were given relevant medicine or water intragastrically， once a day， for consecutive 14 d. The joint tenderness threshold （except for dexamethasone group） and joint swelling index （except for rotundine group） were measured at 0 （before medication）， 3rd and 6th day after administration respectively. HE staining was used to observe the pathological changes of synovial membrane of ankle joint in rats （except for rotundine group）. ELISA assay was used to determine anti-cyclic citrullinated peptide （CCP） antibody in serum of rats （except for rotundine group）， and compatibility index （CI） were calculated. RESULTS： Compared with blank group， joint tenderness threshold of rats were decreased significantly in model group at different time points， while joint swelling index was increased significantly （P＜0.01）. Inflammatory lesions in synovial tissue were obvious， and the content of anti-CCP antibody in serum was significantly increased （P＜0.01）. Compared with model group， the joint tenderness threshold， joint swelling index， synovial tissue pathological changes and anti-CCP antibody content in serum of rats in medication groups were improved in varying degrees， most of the indicators had significant difference （P＜0.05 or P＜0.01）， and the improvement effect of the compatibility groups was better than single component treatment groups. CI value calculated based on anti-CCP antibody content was 0.213，suggesting that the compatibility of the two components had synergistic effect. CONCLUSIONS： The compatibility of A. carmichaeli liposoluble alkaloids and total glucosides of peony in the treatment of wind-cold-dampness type bi-syndrome model rats has analgesia，anti-inflammation and synovial tissue protection， with synergistic efficacy-enhancing effect.

Significance of Anti-Carbamylated Protein Antibody Measurement in the Diagnosis of Rheumatoid Arthritis / 中国医科大学学报

Objective To explore the significance of serum anti-carbamylated protein (anti-CarP) antibody measurement for diagnosing rheumatoid arthritis (RA). Methods In this study, 135 patients with newly diagnosed RA (RA group) and 85 healthy subjects (healthy group) were enrolled. ELISA was performed to measure anti-CarP and anti-cyclic citrullinated peptide (anti-CCP) antibodies. The numbers of swollen and tender joints, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level were recorded. Results Anti-CCP antibody was positive in 106 cases (78.5％) and anti-CarP antibody was positive in 67 cases (49.6％) in the RA group. The sensitivity of combined measurement of anti-CCP and anti-CarP antibodies can improve the specificity of diagnosis, up to 97.6％. Among cases of anti-CarP antibody positivity, the number of swollen and tender joints and DAS-28 score were positively correlated with anti-Car P antibody level (r = 0.61, P = 0.001;r = 0.67, P = 0.001;r = 0.62, P = 0.001, respectively) and weakly correlated with CRP level and ESR (r = 0.28, P =0.015;r = 0.35, P = 0.018, respectively), but not correlated with disease duration (r = 0.09, P = 0.43). A total of 98 cases (72.6％) had radiological changes. At different levels of joint damage severity observed on radiographs, the differences between serum anti-CarP and anti-CCP antibody levels were statistically significant (P ＜ 0.05). Conclusion Combined detection of anti-CarP and anti-CCP antibodies increases diagnostic specificity for RA. Anti-CarP antibody level is also correlated with severity of joint damage, implicating its involvement in the development and progression of RA. It may become an important marker for RA diagnosis, severity evaluation, and prognosis prediction.

Eficacia diagnóstica de anticuerpos antipéptidos citrulinados de segunda y tercera generaciones para la artritis reumatoide / Diagnostic effectiveness of anti-citrullinated peptides antibodies of second and third generations for rheumatoid arthritis

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)

Interpretación de los autoanticuerpos en enfermedades reumatológicas / Interpretation of autoantibodies in rheumatological diseases

RESUMEN Las enfermedades autoinmunes son un grupo de patologías crónicas en las que factores genéticos, ambientales y hormonales contribuyen a su aparición. Además de tener un amplio espectro clínico, la interpretación de los diversos autoanticuerpos y técnicas utilizadas en el laboratorio también son un reto clínico. Dada la complejidad de estas enfermedades, es muy importante apoyarse en las pruebas de laboratorio para establecer un correcto diagnóstico, seguimiento y, en algunos casos inclusive, establecer pronósticos o predicción de la posible aparición de autoinmunidad. Con todo esto se pretende mejorar la calidad de vida de los pacientes disminuyendo la gran morbimortalidad de este grupo de enfermedades, especialmente al diagnosticarlas en etapas tempranas. La mayoría de las enfermedades reumatológicas se caracterizan por la alta producción de autoanticuerpos y reactantes de fase aguda, los cuales están implicados en su fisiopatología produciendo daño directo a nivel sistémico. Entre estas, el lupus eritematoso sistémico, la artritis reumatoide y el síndrome de Sjögren son las más reconocidas. Portales motivos, el objetivo de este trabajo es hacer una revisión que permita guiar tanto a médicos como a personal de laboratorio en la interpretación de los diferentes autoanticuerpos en enfermedades autoinmunes.

ABSTRACT Autoimmune diseases are a group of chronic diseases in which genetic, environmental, and hormonal factors contribute to their appearance. In addition to having a broad clinical spectrum, the interpretation of the various autoantibodies and techniques used in the laboratory is also a clinical challenge. Given the complexity of these diseases, it is very important to rely on the results of laboratory tests to establish a correct diagnosis and follow-up and, in some cases even to establish a prognosis or prediction of autoimmunity. Taking all this into account, it is intended to improve the quality of life of patients by decreasing the increased morbidity and mortality in this group of diseases, especially by early diagnosis. Most rheumatological diseases are characterised by the high production of auto-antibodies and acute phase reactants, which are involved in their pathophysiology, leading to systemic involvement. Among these, the most recognised are, systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome. For these reasons, the objective of this project is to present a review that will help both physicians and laboratory personnel in the interpretation of the different autoantibodies in autoimmune diseases.

Fire-needle Acupuncture Intervention Relieves Ankle-joint Inflammatory Reactions Possibly by Down-regulating Serum TNF-α and Anti-cyclic Citrullinated Peptide Antibody Levels in Collagen-induced Arthritis Rats / 针刺研究

OBJECTIVE: To observe the effect of fire-needle acupuncture of "Zusanli" (ST 36) and "Kunlun" (BL 60) on ankle-joint swelling and serum tumor necrosis factor-α (TNF-α) and anti-cyclic citrullinated peptide antibody (ACPA) contents in collagen-induced arthritis (CIA) rats, so as to study its mechanism underlying improvement of rheumatoid arthritis (RA)．. METHODS: Thirty-two male Wistar rats were randomized into control, model, medication (Methotrexate) and fire-needling groups (n＝8 in each). The RA model was established by injecting type Ⅱ chicken collagen (0.1 mol/L) plus Freund's complete adjuvant (primary immunization) and Freund's incomplete adjuvant (immunization once more) into the subcutaneous tissues of the right foot bottom, back and tail root of rats. Fire-needling was applied to the left and right "Zusanli" (ST 36) and "Kunlun" (BL 60) alternatively for 3 times in each acupoint, once daily for 10 days. For rats of the medication group, Methotrexate sodium chloride solution (0.1 mg/100 g) was administrated by gavage, once every 5 days, twice together. The rats' right hind ankle diameter was measured before and after the treatment. The X-ray film of the right ankle was taken, and the contents of serum TNF-α and ACPA were assayed by ELISA. RESULTS: The ankle diameter and serum concentrations of TNF-α and ACPA were significantly increased in the model group compared to the control group (P0.05). CONCLUSION: Fire-needling stimulation of ST 36 and BL 60, similar to Methotrexate, can relieve the inflammatory reactions of hind-ankle joint in CIA rats, which may be related to its effect in down-regulating ACPA and TNF-α levels.

Clinical value of ELISA combined with colloidal gold immunochromatography in serum anti-CCP antibody detection of patients with rheumatoid arthritis / 中国基层医药

Objective To investigate the clincial value of ELISA combined with colloidal gold immunochromatography in the detection of anti-cyclic citrullinated peptide (CCP) antibody in patients with rheumatoid arthritis (RA).Methods From October 2014 to October 2016,120 patients with RA who admitted to Fuyang People 's Hospital were selected as RA group,and 120 healthy subjects were selected as the control group.Serum samples of patients were collected and tested for anti-CCP antibody by ELISA and ELISA combined with colloidal gold immunochromatography.Results ELISA method was lower than ELISA combined with colloidal gold immunochromatography test (x2 =3.943,P ＜ 0.05).The sensitivity,specificity,positive predictive value,negative predictive value of ELISA combined with colloidal gold immunochromatography assay were 93.33％,91.67％,84.85％,96.49％,respectively,which were higher than single ELISA method (all P ＜ 0.05).Conclusion ELISA combined with colloidal gold imnmunochromatography assay for detection of serum anti-C.CP antibody in patients with RA is effective and can obtain high diagnostic sensitivity and specificity,and it is worthy of promotion.

Clinical efficacy of methotrexate combined with leflunomide in the treatment of rheumatoid arthritis / 中国基层医药

Objective To investigate the clinical efficacy of methotrexate combined with leflunomide in the treatment of rheumatoid arthritis. Methods From January 2017 to February 2018,90 patients with rheumatoid arthritis in Shengzhou Hospital of Traditional Chinese Medicine were divided into control group and observation group according to the random number table method,with 45 cases in each group. The control group was treated with metho-trexate,the observation group was treated with methotrexate and leflunomide. The clinical efficacy of the two groups was evaluated. The anti - cyclic citrullinated peptide antibody (ACCP),rheumatoid factor (RF),and C - reactive protein (CRP) levels were measured before and after 4 months of treatment. The adverse reactions were recorded. Results The total effective rate in the observation group was 95. 56％ after 4 months of treatment,which was signifi-cantly higher than 80. 00％ in the control group (χ2 = 8. 196,P = 0. 016). The ACCP,RF and CRP levels in the two groups were significantly decreased after treatment for 4 months. The ACCP,RF and CRP levels in the observation group were (12423. 68 ± 174. 82) U/ L,(6. 24 ± 2. 14) U/ L,and (6. 69 ± 3. 32) mg/ L,respectively,which were significantly lower than those in the control group [(15421. 27 ± 287. 33) U/ L,(16. 58 ± 3. 26) U/ L,(10. 14 ± 5. 22)mg/ L,t = 59. 787,17. 786,3. 741,P = 0. 000,0. 000,0. 000]. The incidence rate of adverse reaction in the observation group was 6. 67％ ,which in the control group was 4. 44％ ,the difference between the two groups was not statistically significant ( χ2 = 0. 211, P = 0. 645). Conclusion Methotrexate combined with leflunomide in the treatment of rheumatoid arthritis can significantly improve the clinical efficacy,reduce the serum ACCP,RF,CRP levels in patients with a certain degree of control of the disease,while not increasing adverse reactions,has certain degree of safety.

Detection of autoantibodies in serum of patients with coal workers' pneumoconiosis / 中国职业医学

OBJECTIVE: To explore the detection of autoantibodies in serum of patients with coal workers' pneumoconiosis( CWP).METHODS: Eight hundred and three cases of stage Ⅰ CWP patients were selected as study subjects by random sampling method.Anti-nuclear antibody and anti-neutrophil cytoplasmic antibody( ANCA) in serum were detected by indirect immunofluorescence assay; myeloperoxidased efficiency( MPO) antibody,anti-mitochondrial M2 antibody( AMA-M2) and anti-cyclic citrullinated peptide( CCP) antibody were detected by enzyme-linked immunosorbent assay;rheumatoid factor( RF) was detected by enhanced immunoturbidimetry of latexa.Group analysis was conducted according to age,lung function,length of dust exposure and the nature of dust exposure collection.RESULTS: In the serum of 803 CWP patients,the positive rate of anti-nuclear antibody,AMA-M2,RF,anti-CCP antibody,ANCA and MPO antibody were 9.7%,7.5%,7.3%,4.0%,2.6% and 0.8% respectively; the karyotype distribution of 78 cases of anti-nuclear antibody positive specimens was spotted( 43.6%), cytoplasmic( 20.5%), homogenous( 7.7%) and nucleolus( 5.1%),with a titer of 1:100.The positive rate of anti-nuclear antibody in the > 70.0 years group was higher than that of ≤60.0 and ≤70.0 years group( P < 0.017); the positive rate of anti-nuclear antibody in the abnormal lung function group was lower than that of the normal group( P < 0.01); the positive rate of anti-CCP antibody in the dust exposure length > 30.0 years group was higher than that of ≤30.0 years group( P < 0.017); the positive rate of anti-CCP antibody in silica-exposed group was lower than that in the coal-exposed group( P < 0.01).CONCLUSION: The positive rate of antinuclear antibody,AMA-M2,RF and anti-CCP antibody in CWP patients were high.The positive rate of anti-nuclear antibody is associated with age and lung function.The positive rate of anti-CCP antibody is related to the duration and nature of dust exposure.

Independence of carbohydrate-deficient isoforms of transferrin and cyclic citrullinated peptides in rheumatoid arthritis / Independência de isoformas de transferrina deficiente em carboidrato e peptídeos citrulinados cíclicos na artrite reumatoide

ABSTRACT Objective: The aim of this study was to assess the relationship between the two types of posttranslational modifications of proteins in RA: glycosylation on the example of carbohydrate-deficient transferrin and citrullination by means of autoantibodies to cyclic citrullinated peptides. Methods: The study was carried out in 50 RA patients. CDT was measured using N Latex CDT immunonephelometric test, the results were presented in absolute and relative units. Anti-CCP were measured using the chemiluminescent method and rheumatoid factor by immunoturbidimetric method. Results: 80% of RA patients were positive for anti-CCP, 70% for RF and 62% for both, anti-CCP and RF. The level of %CDT was significantly elevated, but absolute CDT level was not changed. The mean absolute CDT concentration was higher in anti-CCP positive patients than that in anti-CCP negative. CDT (absolute and relative concentration) did not correlate with anti-CCP and RF. However, serum RF significantly correlated with anti-CCP. %CDT did not correlate with anti-CCP, but absolute level correlated with anti-CCP only in anti-CCP negative and RF negative patients. CDT did not correlate with RF, but solely with anti-CCP in anti-CCP negative patients. Anti-CCP correlated with DAS 28 only in anti-CCP negative RA, but CDT (absolute and relative units) correlated with DAS 28 in all patients and in anti-CCP positive RA. Conclusions: These results suggest that the changes in CDT and anti-CCP concentrations are not associated with oneself and indicate on the independence of these posttranslational modifications in rheumatoid arthritis. Only the alterations in transferrin glycosylation reflected the activity of RA.

RESUMO Objetivo: Avaliar a relação entre os dois tipos de modificações pós-translacionais de proteínas na AR: glicosilação no caso da transferrina deficiente em carboidrato (TDC) e citrulinação por meio dos anticorpos no caso do antipeptídeo citrulinado cíclico (anti-CCP). Métodos: O estudo foi feito em 50 pacientes com AR. A TDC foi medida com o teste imunonefelométrico N Latex CDT e os resultados foram apresentados em unidades absolutas e relativas. O anti-CCP foi mensurado com o método quimioluminescente e o fator reumatoide (FR) pelo método imunoturbidimétrico. Resultados: Dos pacientes com AR, 80% foram positivos para anti-CCP, 70% para FR e 62% para ambos (anti-CCP e FR). A percentagem de transferrina total (%TDC) esteve significativamente elevada, mas o nível absoluto de TDC não esteve alterado. A concentração média de TDC absoluta foi maior nos pacientes anti-CCP positivos do que naqueles anti-CCP negativos. A TDC (concentração absoluta e relativa) não se correlacionou com o anti-CCP e o FR. No entanto, o FR sérico se correlacionou significativamente com o anti-CCP. O percentual de TDC não se correlacionou com o anti-CCP, mas seu nível absoluto se correlacionou com o anti-CCP apenas em pacientes FR negativos e anti-CCP negativos. A TDC não se correlacionou com o FR, somente com o anti-CCP em pacientes anti-CCP negativos. O anti-CCP se correlacionou com o DAS 28 apenas nos pacientes com AR anti-CCP negativos, mas a TDC (unidades absolutas e relativas) se correlacionou com o DAS 28 quando considerados todos os pacientes com AR e em pacientes com AR anti-CCP positivos. Conclusões: Esses resultados sugerem que as alterações na TDC e as concentrações de anti-CCP não estão associadas e indicam a independência dessas modificações pós-translacionais na artrite reumatoide. Apenas as alterações na glicosilação da transferrina refletem a atividade da AR.

Correlations of Eotaxin-1, rheumatoid factor and anti-cyclic citrullinated peptide antibody with the activity of rheumatoid arthritis / 临床检验杂志

Objective To investigate the correlations of Eotaxin-1,rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody with the activity of rheumatoid arthritis (RA).Methods A total of 58 patients with early RA,46 patients without RA and 53 healthy controls from our hospital during December 2014 and December 2015 were enrolled in our study.The activity of RA was evaluated by the swollen joint count (SJC),tender joint count (TJC) and DAS28 score.The levels of serum Eotaxin-1 and antiCCP antibody were detected by ELISA and serum RF levels were determined by the immunological turbidimetry.The comparisons of serum Eotaxin-1,anti-CCP antibody and RF levels between different groups were performed with ANOVA and their correlations with SJC,TJC and DAS28 score were analyzed by Spearman rank correlation.Results The levels of Eotaxin-1,anti-CCP antibody and RF in RA patients were (96.02 ± 2 1.07) pg/mL,(183.42 ± 87.45) U/mL and (119.09 ± 62.30) RU/mL,respectively,which were significantly higher than those in the patients without RA and healthy controls (P ＜ 0.01).The levels of serum Eotaxin-1 in RA patients were significantly related to TJC,SJC and DAS28 score (P ＜ 0.01),while the levels of anti-CCP antibody were related to TJC and DAS28 score.The levels of RF were only related to DAS28 score.Conclusion The levels of serum Eotaxin-1 and anti-CCP antibody in RA patients are significantly correlated with the activity of RA,which may be new serum markers to monitor the activity of RA.

Study on immunogenicity and arthritogenicity of a synthetic cyclic citrullina-ted peptide / 中国免疫学杂志

Objective:To establish a synthetic cyclic citrullinated peptide induced arthritis model in mice, explore immunogenicity and arthritogenicity of this peptide. Methods: 36 DBA/1 mice were randomly divided into three groups, which were injected the type Ⅱ collagen ( CⅡ, CIA ) emulsion, cyclic citrullinated vimentin peptide ( CCit-Vim, CCV-IA ) emulsion, cyclic citrullinated vimentin peptide conjugated KLH ( CCit-Vim+KLH,CCV+K-IA) emulsion on day 0 and 21,respectively. Using arthritis index( AI) ,paw swelling to evaluate the incidence of arthritis;ELISA tested serum anti-CCit-Vim antibody,anti-CⅡantibody,anti-CCP antibody and TNF-α, IIF detected AKA;Histopathology of the ankle joint was obsearved. Results: There were three mice appeared arthritis in CCV+K-IA,the incidence rate of 25%,but arthritis occurs later time,short duration,and the incidence and extent of arthritis were lower than the CIA. CCV-IA no arthritis performance. CCV+K-IA produce anti-CCit-Vim antibody were significantly higher than those in CIA (1. 32±0. 59 vs 0. 78±0. 27,P=0. 031). While Anti-CCP antibody of CCV+K-IA were significantly lower than CIA (54. 73±7. 33 vs 64. 37±9. 91,P=0. 007). The anti-CⅡ antibody in CCV+K-IA and CCV-IA were lower than the CIA(15. 73±2. 10, 16. 71±3. 03 vs 19. 50±2. 36,P<0. 05). The TNF-α produced by CCV+K-IA and CIA were both significantly higher than the CCV-IA (645. 61±35. 26,618. 98±53. 32 vs 533. 63±79. 49,P<0. 05). The AKA positive rate of CCV+K-IA is 50% (6/12),significantly higher than CCV-IA 25% ( 3/12 ) and CIA 16. 67% ( 2/12 ) . Histopathology of the ankle showed that the CCV-IA and CCV+K-IA have a mild synovial hyperplasia,no obvious synovial pannus formation and inflammatory cell infiltration. Conclusion:The cyclic citrul-linated peptide conjugated KLH not only has stronger immunogenicity but also has arthritogenicity. It induced a higher positive rate of AKA than CⅡ.

The clinical significance of rheumatoid arthritis merger antinuclear antibody positive / 国际检验医学杂志

Objective To understand the fluorescence pattern of antinuclear antibody(ANA)and the distribution of target anti-gen and ANA′s impact on rheumatoid arthritis(RA)RA.Methods The data of rheumatoid factor(RF)and anti-cyclic citrullinated peptide antibodies(anti-CCP antibodies)and ANA of 860 RA patients during 2014-2015 were collected and divided into 2 groups according to the ANA levels.The differences of RF and anti-CCP antibodies level between 2 groups were analyzed.Analyzed the fluorescence pattern of RA merger ANA and the distribution of target antigen by statistical.Results Of the 860 RA patients,the positive rate of ANA was 37.6%,the major fluorescence pattern of RA merger ANA was speckled pattern,anti SSA positive rate was 21.7%.The RF and anti-CCP antibodies level had statistical difference between ANA positive group and ANA negative group (P <0.05).Conclusion RA merger ANA positive can show different fluorescence patterns and target antigen,the speckled pattern and anti-SSA positive are the main pattern.The severity of arthritis symptoms and the degree of bone destruction between ANA positive group and ANA negative group were difference.Anti-ANA positive has a certain promoting effect on the progression of RA disease.

Application value of anti-CCP antibody ,RF ,ESR and CRP detection in diagnosis of RA / 国际检验医学杂志

Objective To investigate the changes of anti-cyclic citrullinated peptide antibody ,rheumatoid factor (RF) ,erythrocyte sedimentation rate(ESR) and C reactive protein(CRP) levels in the patients with early rheumatoid arthritis (RA) and their applica-tion value in the diagnosis and treatment.Methods A total of 210 cases of early RA in sixth affiliated hospital of Guangzhou Medi-cal University from December 2015 to June 2016 were selected as the RA group ,including 28 males and 182 females ,at the same time 115 cases of other rheumatism were selected as the non-RA group ,male ,including 38 males and 77 females.85 persons under-going the healthy physical examination were taken as the health group ,including 46 males and 39 females.The latex enhanced im-mune turbidimetry was adopted to quantitatively detect anti-cyclic citrullinated peptide antibody.The RF and CRP levels were quan-titatively detected by using the immune turbidimetry.The Westergren method was used to test the ESR ,their content changes in RA ,non-RA arthritis and other autoimmune diseases were detected.Results The sensitivity ,specificity ,positive predictive value , negative predictive value and Youden index of anti-cyclic citrullinated peptide antibody in the RA group were 60.95% ,97.64% , 98.46% ,50.30% and 0.59 respectively ,which of RF test were 52.38% ,95.29% ,96.49% ,44.75% and 0.48 respectively ,which of CRP test were 30.48% ,89.41% ,87.67% ,87.67% ,34.23% and 0.20 respectively ,which of ESR test were 49.52% ,87.06% , 90.43% ,41.11% and 0.37 respectively.Anti-cyclic citrullinated peptide antibody detection in the RA group was obviously higher than that of the RF test ,their test results were obviously higher than those of the non-RA group and healthy group ,the differences were statistically significant (P0.05).Conclusion Anti-cyclic citrullinated peptide antibody level is higher in the patients with RA ,which is signifi-cantly superior to the RF test ,and anti-cyclic citrullinated peptide antibody detection has higher value for early diagnosis of RA.

Value of anti-mutated citrullinated vimentin antibody and anti-cyclic citrullinated peptide antibody in the prediction of bone erosion and disease activity of rheumatoid arthritis / 中华风湿病学杂志

Objective To investigate the relationship between anti mutated citrullinated vimentin (MCV) antibody, anti-cyclic citrullinated peptide (CCP) antibody with disease activity and bone erosion in patients with rheumatoid arthritis (RA), so as to provide evidence for clinical diagnosis and treatment. Methods The anti-CCP antibody and anti-MCV antibody were detected using the enzyme-linked immune adsorption method (ELISA) for 634 patients with RA. At the same time, the clinical and laboratory data were collected, and the X-ray images of hands or feet were taken. Disease activity score (DAS)28 score was calculated, and all patients were divided into high disease activity group, moderatedisease activity group, low disease activity group and stable disease group on the basis of the DAS28 score. We analyzed the relationship between the degree of anti MCV, anti CCP antibodies, and disease activity of patients by Spearman correlation. And anti CCP, anti MCV antibodies, erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) of these patients were compared at different period of bone erosion and disease activity by the Wilcoxon rank sum test and nemenyi. Results ① Positive correlation could be detected between anti-MCV antibody and ESR, CRP, number of tender joint, DAS28 score (r=0.115, P=0.004; r=0.120, P=0.003; r=0.124, P=0.002; r=0.085, P=0.032), and anti CCP antibody had no correlation with these index. The anti MCV antibodies in high disease activity group [694 (156, 1 000)] U/ml, and moderate activity group [911 (190, 1 000)] U/ml were higher than that of the low disease activity [248(150, 731)] U/ml or stable group [275(62, 928)] U/ml (U=2.29, P=0.023;U=2.25, P=0.024; U=2.45, P=0.014; U=2.4, P=0.018), and anti CCP antibody in the moderate disease activity group [499(180, 1 370)] U/ml was higher than low disease activity group [297(83, 574)] U/ml and stable group [187(67, 1 153)] U/ml (U=2.53, P=0.012; U=2.22, P=0.026). ②The anti MCV, anti CCP antibody in the bone erosion group were higher than those without bone erosion group (U=4.64, P<0.01;U=2.69, P=0.007). The anti MCV antibodies in stage Ⅱ[722(259, 1 000)] U/ml and Ⅲ group [714 (216, 1 000)] U/ml was significantly higher than that in stage Ⅰ [316(98, 1 000)] U/ml(U=3.46, P<0.01; U=4.28, P<0.01). The anti CCP antibody level in stage Ⅱ [394(180, 1 000)] U/ml and Ⅲ[391(181,1305)] U/ml was higher compared with stage Ⅰ[277 (98,898)] U/ml (U=1.99, P=0.046; U=2.92, P=0.004), and that in phase Ⅲ was higher than Ⅳ [218(71, 911)] U/ml (U=2.06, P=0.041). Conclusion Compared with anti-CCP antibody, anti-MCV antibody is closely related with disease activity, and has a better predictive value for bone erosion. Patients with higher ESR and CRP are more susceptible to bone erosion.