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Surface plasmon resonance (SPR) sensors have been used for detection of various biomolecules because of their simplicity, high specificity and sensitivity, real-time detection, low cost, and no requirement of labeling. Recently, molecularly imprinted polymers that are easy to prepare, less expensive, stable, have talent for molecular recognition and also are used for creation selective binding sites for target molecule on the SPR sensors. Here, we show that preparation of cyclic citrullinated peptide antibody (anti-CCP) imprinted SPR sensor to detect CCP antibodies. For this purpose, anti-CCP/AAm pre-complex was synthesized by interacting acrylamide (AAm) monomer with anti-CCP. Then, anti-CCP imprinted (anti-CCP/PAAm) SPR sensor was obtained by reacting with anti-CCP/AAm pre-complex in the presence of the crosslinker, and initiator/activator pair. Besides this, non-imprinted (PAAm) SPR sensor was also prepared without using anti-CCP template. The SPR sensors were characterized and then adsorption-desorption studies were performed with pH 7.0 phosphate buffer (10 mM) and acetic acid (10%) with Tween 20 (1%) in pH 7.0 phosphate buffer. Selectivitiy of sensors was investigated by using immunoglobulin M (IgM) and bovine serum albumin (BSA). To determine the adsorption model of interactions between anti-CCP solutions and anti-CCP/PAAm SPR sensor, different adsorption models were performed. The calculated maximum reflection, detection limit, association and dissociation constants were 1.079 RU/mL, 0.177 RU/mL, 0.589 RU/mL and 1.697 mL/RU, respectively. Repeatability experiments of anti-CCP/PAAm SPR sensor was performed four times with adsorption-desorption-regeneration cycles without any performance losing. Results showed that anti-CCP/PAAm SPR sensor had high selectivity and sensitivity for detection of CCP antibodies. [ABSTRACT FROM AUTHOR]

OBJETIVOS: Avaliar a associação do anticorpo antipeptídeo citrulinado cíclico (anti-CCP) com distintos parâmetros clínicos, sorológicos e radiológicos. MÉTODOS: Anti-CCP e fator reumatóide (FR) foram pesquisados no soro de 100 pacientes com artrite reumatóide (AR). A atividade da doença foi definida por meio de um índice combinado compreendendo cinco parâmetros: número de juntas inflamadas, número de juntas doloridas, rigidez matinal, escala visual analógica (EVA) de dor e velocidade de hemossedimentação (VHS). A capacidade funcional foi medida pelo índice HAQ (Health Assessment Questionnaire) e a classe funcional foi determinada mediante aplicação dos critérios revisados do American College of Rheumatology (ACR), de 1991. Erosão e pinçamento articular foram graduados pelo índice de Sharp modificado. A análise estatística empregou os testes do Qui-quadrado, Mann Whitney e Kruskal-Wallis. RESULTADOS: Nenhum dos dois anticorpos demonstrou associação significativa com atividade da doença, sexo, idade de início da doença, presença de nódulos subcutâneos e síndrome de Sjögren. A média de idade foi significativamente menor nos pacientes com AR anti-CCP positivos. A positividade para o FR e anti-CCP foi maior nos pacientes com AR com menos de 50 anos em comparação com os pacientes com mais de 50 anos. A AR de início recente (< 2 anos) não se associou a uma maior prevalência de soropositividade para o anti-CCP e FR. O anti-CCP apresentou uma correlação positiva moderada com o FR. Houve uma correlação direta entre o anti-CCP e a VHS e a proteína C reativa (PCR). Houve também uma correlação direta entre o FR, a VHS e a PCR. A classificação funcional dos critérios revisados do ACR de 1991 não se associou a qualquer dos dois auto-anticorpos. O índice de HAQ não se correlacionou com a atividade da doença, duração da doença, positividade do FR e atividade medida pela PCR, mas associou-se nitidamente à positividade do anti-CCP e à atividade medida pelo VHS. Os índices de Sharp para erosão e pinçamento se associaram à positividade do anti-CCP. Tal associação não foi evidenciada com a positividade do FR. CONCLUSÃO: Embora o anti-CCP apresente boas propriedades diagnósticas, ele não apresenta associação com a atividade da doença, sexo, idade de início da doença, tempo de evolução de doença, presença de nódulos subcutâneos, síndrome de Sjögren ou classificação funcional do ACR de 1991. Houve associação da positividade do anti-CCP com a menor idade dos pacientes, fator reumatóide, VHS, PCR, índice de HAQ e índices de Sharp para erosão e pinçamento.OBJECTIVE: Evaluate the association of Anti-Cyclic Citrullinated Peptide Antibody (anti-CCP) with distinct clinic, serological and radiological parameters. METHODS: anti-CCP and rheumatoid factor (RF) were determined in the serum of 100 patients with rheumatoid arthritis (RA). Disease activity was defined by means of a combined index with five parameters: number of swollen joints, number of painful joints, morning stiffness, pain visual analogue scale (VAS), and erythrocyte sedimentation rate (ESR). Functional capacity was measured by (Health Assessment Questionnaire) HAQ index and the functional class was ascribed according to American College of Rheumatology criteria (1991). Articular erosion and narrowing were estimated by the modified Sharp's index. Statistical analysis was performed by chi-square, Mann-Whitney, and Kruskal-Wallis tests. A value of less 0.05 was considered significant. RESULTS: None of the two antibodies showed association with disease flare, gender, age in the time of diagnosis, secondary Sjögren's syndrome or subcutaneous nodules. The mean age was significantly lower in RA patients with positive anti-CCP. The RF and anti-CCP positivity was higher in RA patients below 50 years old than patients above 50 years old. The early RA, up to 2 years of evolution, was not associated with a higher prevalence of anti-CCP and RF reactivity. Anti-CCP showed direct moderate correlation to RF and also direct correlation to ESR and CRP. FR reactivity showed direct correlation to ESR and CRP. Functional class showed no association with neither autoantibodies. HAQ index showed correlation with anti-CCP-positive patients and activity assessed by ESR, but did not show association with disease activity, disease duration, presence of the RF and activity assessed by ESR. Sharp's erosion and narrowing index showed association to presence of anti-CCP, but not with RF positive patients. CONCLUSIONS: Although anti-CCP displays good diagnosis properties for RA, it appears not to be associated with activity disease, gender, age at the disease beginning, disease evolution, presence of the secondary Sjögren's syndrome and subcutaneous nodules or functional class. Anti-CCP reactivity showed association with early patients, RF positivity, ESR, CRP, HAQ index or Sharp'erosion and narrowing index.

Background Patients with rheumatoid arthritis (RA) have increased coronary atherosclerosis possibly related to several factors including insulin resistance. Anti-CCP antibodies are highly specific for RA but their association with cardiovascular morbidity has not been examined by enough studies. Aim The aim of this study was to evaluate the role of anti ccp antibodies and IR for detection of early and sub-clinical atherosclerosis in RA patients. Subjects and methods 56 RA patients and 19 age and sex matched healthy subjects were included in the present study. All patients and controls were subjected to full history, clinical examination, and laboratory investigations (including CBC, ESR, high sensitive CRP, rheumatoid factor and lipid profile). All patients were also subjected to measurement of intima-media thickness (IMT) of both carotid arteries as well as the flow mediated dilatation (FMD) of brachial artery. Also, measurements of IR (by HOMA 2) and anti-CCP were done for all subjects. Results IMT was significantly increased ( P = 0.01) and FMD significantly decreased ( P = 0.001) in RA patients than controls in spite of the absence of significant differences in traditional atherosclerotic risk factors. Both IR and anti-CCP (which are significantly increased in RA compared to controls, P = 0.02 and 0.001 respectively ) were significantly positively correlated to IMT ( P = 0.009 and 0.001 respectively ) and negatively correlated to FMD ( P = 0.0005 and 0.005 respectively ). Conclusion IR and anti-CCP may be helpful in the early detection of subclinical atherosclerosis in RA patients. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a neglected disease in tropical countries. Clinical and laboratory features may mimic autoimmune diseases and this can complicate the Leishmania diagnosis. Due to our previous investigation for false anti-CCP2 reactivity in Leishmania -infected subjects and our interest in immunity against the joint-specific collagen type II (CII) in rheumatoid arthritis (RA) we investigated the same cohort for anti-CII antibodies. We found elevated anti-CII reactivity in Leishmania -infected patients as compared to controls. When anti-CII OD values were compared with BSA-blocked control plates we found higher reactivity against BSA than in CII-coated plates in many Leishmania -infected patients. The percentage of such false positive anti-CII reactions increased with inflammatory activity, and was found in almost all Leishmania patients with highly active inflammatory disease, but was as low in Sudanese healthy controls as well as among Swedish RA patients. The correlation coefficients between false positive anti-CII and anti-CCP2 measured with a commercial ELISA were highest for patients with the most inflammatory disease but non-significant for Sudanese controls and Swedish RA patients, arguing that our findings may have general implications for ELISA measurements in leishmaniasis. ELISA investigations in areas endemic for leishmaniasis might benefit from individual-specific control wells for each serum sample. This approach might also be applicable to other geographical areas or patient groups with high incidence of inflammatory and infectious diseases. [ABSTRACT FROM AUTHOR]

In this study we determined the frequency, sensitivity and specificity of anti cyclic citrullinated peptides (anti-CCP) IgG antibody, total rheumatoid factor (RF-T), and RF isotypes in Iranian patients with rheumatoid arthritis (RA) and their association with age, clinical and serological parameters. Anti-CCP and RF-T and RF isotypes level were measured in 418 patients and 399 healthy controls by enzyme-linked immunosurbant assay (ELISA). Additionally, serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), visual analog scale (VAS) and disease activity score (DAS28) were evaluated in RA patients. The anti-CCP was positive in 53.1% of RA patients and 4.7% of controls. The frequency of RF-T was 61.87% and 17.66% in RA patients and controls respectively. The prevalence of RF isotypes in RA patients was 46.52% for RF-IgM, 23.47% for RF-IgA and 21.74% for RF-IgG. 31.39% of RA patients were RF-IgM positive without RF-IgA and RF-IgG and 21.9% were positive for all three RF classes. The anti-CCP positive patients showed increased number of swollen joints. On the other hand, RF-T positive patients exhibited a longer disease duration, lower age of onset and also higher ESR, CRP level and increased swollen joints. RF-T titer was significantly higher in RA patients with active disease compared to remission, low and moderate active groups. The sensitivity and specificity were 53.1, 95.3 for anti-CCP antibody and 61.8, 82.3 for RF-T. Our results support that anti-CCP and RF titer maybe valuable in estimation of disease activity and other inflammatory parameters in RA patients.

Introduction: Rheumatoid arthritis (RA) is the most common inflammatory joint disease. Various proinflammatory cytokines are involved in the pathogenesis of this chronic disorder. It is characterized by the presence of autoantibodies, such as rheumatoid factor and antibodies against citrullinated peptides. The present study focuses on investigation of possible association between the proinflammatory cytokine interleukin 17 and anti-CCP, anti-MCV, and anti-CarP antibodies seropositivity in RA patients., Aim: To assess serum levels of interleukin 17 (IL-17) in patients with rheumatoid arthritis and healthy controls (HC) and to investigate the relationship between IL-17 and anti-cyclic citrullinated protein (anti-CCP) antibodies, antimutated citrullinated vimentin (anti-MCV) antibodies, and anti-carbamylated protein (anti-CarP) antibodies in patients with RA., Materials and Methods: Forty-seven patients diagnosed with rheumatoid arthritis and 44 healthy controls were included in the study. Serum IL-17 levels were examined in all participants. Anti-CCP, anti-MCV, and anti-CarP antibodies were tested in the group of RA patients., Results: The mean serum level of IL-17 in RA patients was higher (12.8 pg/ml) than that in healthy controls (7.9 pg/ml), but the difference was not statistically significant (p=0.276). No significant correlation was observed between anti-CCP (+/-) and IL-17 (rs=0.162, p=0.380), and between anti-MCV (+/-) and IL-17 (rs=0.157, p=0.340). A significant positive correlation of moderate value was reported between anti-CarP (+/-) and IL-17 (rs=0.388, p=0.015)., Conclusions: The present study demonstrated that the IL-17 serum levels in RA patients were increased compared to healthy controls. No correlation was found between ACPA immunological markers and IL-17 levels in patients with RA. A positive correlation was found between anti-CarP antibodies and IL-17 in the patients' group. The increased level of IL-17 is suggestive of its possible role in the pathogenesis of CarP positive RA patients., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Immune dysregulation plays an important role in the pathogenesis of rheumatoid arthritis (RA). The CD4+CD25 high FoxP3+ subset of regulatory T cells plays an essential role in preventing autoimmunity and maintaining immune homeostasis. Negative regulation of JAK/STAT signaling is controlled by Suppressor of Cytokine Signaling (SOCs3) proteins. SOCs is produced at lower levels in RA. Our aim was to evaluate the expressional dysregulation of SOCs3 and FoxP3 genes in RA patients in relation to disease activity., Methods: We have recruited 90 patients with RA and 60 healthy controls in case control study. Whole blood samples were collected from RA patients and healthy subjects. The measurement of FoxP3 and SOCs3 gene expression was performed by real-time PCR (qPCR)., Results: Patients with RA had significantly decreased expression levels of FoxP3 and SOCs3 genes in comparison with controls (P<0.001), in addition to the insignificance correlation of both genes with disease activity in RA patients., Conclusion: FoxP3 and SOCs3 genes showed significant defects in rheumatoid arthritis patients with no significant difference in disease activity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

We assessed the clinical feasibility of conducting immunoassays based on surface-enhanced Raman scattering (SERS) in the early diagnosis of rheumatoid arthritis (RA). An autoantibody against citrullinated peptide (anti-CCP) was used as a biomarker, magnetic beads conjugated with CCP were used as substrates, and the SERS nanotags were comprised of anti-human IgG-conjugated hollow gold nanospheres (HGNs). We were able to determine the anti-CCP serum levels successfully by observing the distinctive Raman intensities corresponding to the SERS nanotags. At high concentrations of anti-CCP (>25 U/mL), the results obtained from the SERS assay confirmed those obtained via an ELISA-based assay. Nevertheless, quantitation via our SERS-based assay is significantly more accurate at low concentrations (<25 U/mL). In this study, we compared the results of an anti-CCP assay of 74 clinical blood samples obtained from the SERS-based assay to that of a commercial ELISA kit. The results of the anti-CCP-positive group ( n = 31, >25 U/mL) revealed a good correlation between the ELISA and SERS-based assays. However, in the anti-CCP-negative group ( n = 43, <25 U/mL), the SERS-based assay was shown to be more reproducible. Accordingly, we suggest that SERS-based assays are novel and potentially useful tools in the early diagnosis of RA. [ABSTRACT FROM AUTHOR]

Stimulation of the vagus nerve suppresses cytokine production and macrophage activation, via the interaction of its neurotransmitter acetylcholine (ACh) with the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR), present on neurons and inflammatory cells. The present study aimed to verify the potential anti-inflammatory effect of galantamine against experimental arthritis induced in rats. Fourteen days post adjuvant injection, Sprague-Dawley rats were treated orally with three doses of galantamine (1.25, 2.5 and 5 mg/kg) or leflunomide (10 mg/kg) for 2 weeks and arthritis progression was assessed by hind paw swelling. Additionally, serum biomarkers, viz ., anti-cyclic citrullinated peptide antibodies (Anti-CCP), tumor necrosis factor- α (TNF- α ), interleukin-10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) were measured. Radiological examination of the hind paws was also carried out to evaluate the degree of joint damage. Adjuvant arthritis led to a significant weight loss, marked swelling of the hind paw and alteration in the serum levels of anti-CCP, TNF- α , IL-10 and MCP-1. These alterations were associated with significant radiological changes of the joints. Galantamine, in a dose-dependent manner, reduced significantly all biomarkers of inflammation, with the highest dose showing the best beneficial anti-inflammatory effect that was superior in magnitude to the reference drug leflunomide in most of the studied parameters. In conclusion, these results suggest that galantamine may represent a novel, inexpensive and effective therapeutic strategy in the treatment of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The genes encoding protein tyrosine phosphatase non-receptor type 22 (PTPN22) and signal transducer and activator of transcription 4 (STAT4) have been reported to be associated with RA in several ethnic populations. Objectives: This work aims to assess the association between PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with RA susceptibility through an updated meta-analysis of available case-control studies. Methods: A literature search of all relevant studies published from January 2007 up to December 2014 was conducted using Pubmed and Science Direct databases. The observed studies that were related to an association between PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with RA susceptibility were identified. Meta-analyis of the pooled and stratified data was done and assessed using varied genetic models. Results: Thirty-seven case-control studies with a total of 47 comparisons (29 for PTPN22 rs2476601 polymorphism and 18 for STAT4 rs7574865 polymorphism) met our inclusion criteria. The meta-analysis showed an association between PTPN22 T allele, CT+TT and TT genotypes with RA susceptibility. Furthermore, The meta-analysis showed an association between STAT4 T allele, GT+TT and TT genotypes with RA susceptibility. Stratification of RA patients according to ethnic groups showed that PTPN22 T allele, CT+TT genotypes, STAT4 T allele and STAT4 GT+TT were significantly associated with RA in European, Asian, African subjects, while PTPN22 TT genotype was significantly associated with RA in European but not in Asian and African subjects and STAT4 TT genotype was significantly associated with RA in European and Asian but not in African subject. A subgroup analysis according to the presence or absence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies revealed that the association between PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with RA susceptibility may not be dependent on RF and anti-CCP antibodies. Conclusions: Our meta-analysis demonstrated that PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms confers susceptibility to RA in total subjects and in major ethnic groups. The association may not be dependent on RF and anti-CCP antibodies. [ABSTRACT FROM AUTHOR]

Background/Aims: Arthropathy is the most common extraintestinal manifestation observed in patients with Crohn's disease (CD). The present study aimed to screen rheumatoid arthritis (RA) using anti-CCP antibodies and rheumatoid factor (RF) in CD patients from Southern Brazil. Additionally, the presence of arthralgia and spondyloarthritis (SpA) was evaluated. CD patients, previously diagnosed using clinical data, imaging tests, endoscopic and histological findings, were included consecutively. Methods: A total of 100 patients participated in the study, of which 60% were female, with a mean age of 41.9 ± 12.04 (16-83 years). As controls, sera from 100 healthy individuals from the same geographic area were analyzed. Results: Arthralgias were present in 55% of the patients, being more frequent in women (65.5%; 36/55), than in males (34.5%). No association was found between arthralgia and the treatment method used. Six patients (6/100) had SpA previously diagnosed. In the CD group, anti-CCP was positive only in one patient, while RF was positive in 7 patients (7%; 7/100). The anti-CCP positive patient (woman, 38 years old, RF positive), fulfilled the ACR criteria and was diagnosed as RA. In the control group, anti-CCP antibodies were detected in 1% (1/100) and RF was positive in 6 of the samples (6%). Conclusion: Our data showed low frequency of anti-CCP antibodies and RF in Brazilian patients with CD. Additionally, we found a high prevalence of arthralgia in these patients, with 6% of them diagnosed with SpA. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background The gene encoding cytotoxic T lymphocyte associated antigen-4 ( CTLA-4 ) has been reported to be associated with rheumatoid arthritis (RA) in several ethnic populations. The aim of this work is to assess the association of this polymorphism with the susceptibility, activity and functional disability of RA in Egyptian subjects. Subjects and methods This study included 112 unrelated RA Egyptian patients who were compared to 122 healthy controls from the same locality. For all subjects, DNA was genotyped for CTLA-4 + 49 A>G ( rs231775 ) polymorphism using the PCR-RFLP technique. Antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). Results The frequency of the CTLA-4 G allele was significantly higher among cases compared to controls (37.1% vs. 23.4%, OR = 1.93; 95% CI = 1.29–2.89, p = 0.002). Also, the frequency of CTLA-4 + 49 G allele carriage ( AG+GG genotypes) was significantly higher among cases with RA compared to controls (61.6% vs. 41.8%, OR = 2.23, 95% CI = 1.32–3.77, p = 0.003). Logistic regression analysis showed that cases positive to the G allele ( GA+GG genotypes) had less frequency of rheumatoid deformities and also a lower DAS28-CRP score, yet with a higher visual analogue scale (VAS) i.e. more functional disability than other cases. Conclusions CTLA-4 + 49 G allele carriage was associated with increased susceptibility and functional disability of RA in Egyptian patients. [ABSTRACT FROM AUTHOR]

Aim To evaluate the prevalence and diagnostic significance of the autoantibody against citrullinated vimentin (anti-Sa) compared with the widely used anti-cyclic citrullinated peptide autoantibody (anti- CCP) in patients with rheumatoid arthritis ( RA). Method One hundred and sixty-nine patients hospitalized at the Department of Rheumatology and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland, were enrolled in a cross-sectional study and divided into two groups. The RA group comprised 41 patients diagnosed as having RA. The non- RA control group included 128 individuals with a variety of rheumatic disorders. Serum anti-Sa and anti- CCP measurements were performed by enzyme-linked immunosorbent assay. Results The sensitivity and specificity of anti-Sa for the diagnosis of RA was 36.6% and 96.9%, respectively. For the anti- CCP test, the sensitivity was 65.9% and the specificity was 95.3%. Concomitant presence of anti-Sa and anti- CCP was determined in 36.6% of the patients with RA, whereas isolated positivity of anti-Sa was not observed. Anti-Sa positive RA patients had significantly higher anti- CCP levels compared to anti-Sa negative subjects ( P < 0.05). Conclusion With regard to the relatively low diagnostic sensitivity and the lack of cases identified by anti-Sa alone, we were unable to demonstrate any additional diagnostic value of the anti-Sa autoantibody in comparison to the anti- CCP autoantibody. To the authors' best knowledge, this is the first study among Polish patients verifying the clinical utility of anti-Sa in the diagnosis of RA. [ABSTRACT FROM AUTHOR]

Citrullination, a post-translational modification of proteins, is increased in inflammatory processes and is known to occur in smokers. It can induce anti-cyclic citrullinated peptide (CCP) antibodies, the most specific serologic marker for rheumatoid arthritis. Thus far, the incidence of autoimmunity in patients with wood-smoke-induced chronic obstructive pulmonary disease (COPD) resulting in anti-CCP production has not been examined. We hypothesise that anti-CCP antibody level in these patients should be higher than that in healthy subjects. A total of 112 non-rheumatoid arthritis patients, including 56 patients with wood-smoke-induced COPD and 56 patients with tobacco-induced COPD, and 56 healthy non-smoker controls were included. The serum anti-CCP antibody levels were measured and compared between the groups and against smoke exposure and clinical characteristics. The mean anti-CCP antibody levels in wood-smoke-induced COPD group were significantly higher than those in tobacco-induced COPD group ( p = 0.03) and controls ( p = 0.004). Furthermore, 8 (14.2 %) patients with wood-smoke-induced COPD, 4 (7.14 %) with tobacco-induced COPD and 2 (3.57 %) controls exceeded the conventional cut-off of anti-CCP antibody positivity. No relationship was found between the anti-CCP antibody level and age, gender, duration of disease, Pack-years of smoking, and duration of exposure to wood smoke. Moreover, correlations between anti-CCP antibodies and severity of airflow limitation, CAT scores, mMRC scores of dyspnoea, and GOLD staging of COPD severity were not significant. Wood-smoke-induced COPD could significantly increase the anti-CCP antibody level in non-rheumatoid arthritis patients when compared with that in patients with tobacco-induced COPD and healthy controls. [ABSTRACT FROM AUTHOR]

Protein citrullination and degradation by matrix metalloproteinases (MMP) plays a central role in the pathology of rheumatoid arthritis (RA). Autoantibodies are known to target citrullinated vimentin. The aim of this study was to investigate the relationship between the blood levels of MMP-degraded and citrullinated vimentin (VICM), as compared with the levels of MMP-degraded and non-citrullinated vimentin (VIM), and the standard anti-CCP biomarker in RA patients undergoing treatment. Thus, VIM, VICM and anti-CCP were quantified by ELISA in serum samples from baseline and week 8 of patients (n = 257) with RA, treated with either tocilizumab (8 mg/kg), methotrexate (7.5−15 mg/kg) or a placebo and compared with a reference cohort (n = 64). The three biomarkers were elevated in RA serum compared with the reference cohort: medians were 1.7 vs. 0.8 ng/mL (p < 0.05) for VIM; 7.5 vs. 0.7 ng/mL (p < 0.0001) for VICM; 57 vs. 4 RU/mL (p < 0.001) for anti-CCP. VICM was decreased in response to tocilizumab (2.9-fold, p < 0.0001) and to methotrexate (1.5-fold, p < 0.05) compared with the placebo, while anti-CCP was not. Serum VIM was also modulated by both drugs, although to a lesser degree. A high baseline level of VICM was predictive of a low disease activity response at week 8. In conclusion, VICM can differentiate between RA and healthy donors in a similar manner to anti-CCP; furthermore, VICM is also a pharmacodynamic marker.

Currently the markers for the diagnosis of rheumatoid arthritis include inflammatory makers (including blood sedimentation and C-reactive protein), immune complexe and complement detection, detection of joint synovial fluid, and detection of autoantibodies. These indicators change with the activity of arthritis. Early diagnosis relies mainly on detection of autoantibodies. Anti-cyclic citrullinated peptide antibody (anti-CCP) is a kind of anti-keratin antibody, having higher sensitivity and specificity than the rheumatoid factor in diagnosis of rheumatoid arthritis. During the first year of rheumatoid arthritis, the existence of anti-CCP can be detected in the serum of most of these people. Positive anti-CCP can also be used to predict serious damage. Therefore, anti-CCP is extremely helpful in early diagnosis and prognosis assessment of rheumatoid arthritis. In this paper, the recent application of anti-CCP in the diagnosis of rheumatoid arthritis is reviewed. [ABSTRACT FROM AUTHOR]

Purpose: To determine the value of Anti-CCP as predictor for disease activity in rheumatoid arthritis assessed by DAS- 28, and to find the effect of smoking on disease activity in rheumatoid arthritis. Materials and Methods: One hundred patients with rheumatoid arthritis involved in this study, consisted of 88 female and 12 male who fulfilled the 2010 ACR-EULAR classification criteria for rheumatoid arthritis attending the rheumatology department in general hospital, or attended the center of rheumatology and rehabilitation in sulaimani city, for 6 months (from October, 2012 to March, 2013). Thorough Demographic information of patients was recorded through history of age, sex, and history of smoking, disease duration, physical evaluation according to DAS-28. and serological test for RF and Anti-CCP. Results: There was highly significant association between DAS-28 and Anti-CCP value (p =0.0001). there was no significant correlation between DAS-28 and RF (p= 0.252),According to smoking there was highly significant association between smoking with Anti-CCP value and DAS-28 (p=0.003- 0.0001) respectively while there was no significant association between smoking and RF(p=0.15). Conclusion: A highly significant correlation was found between Anti-CCP value and disease activity in rheumatoid arthritis, smoker patients had higher value of Anti-CCP compared to non-smoker patients. Smokers demonstrated a more active and severe disease activity compared to non-smokers. [ABSTRACT FROM AUTHOR]

ACPA (anti-citrullinated protein antibody) tests are today systematically added to clinical and radiological investigations when diagnosing rheumatoid arthritis (RA), and the inclusion of ACPA positivity in the new 2010 RA criteria underlines their importance. The aim of this study was to determine the sensitivity and specificity of different ACPA assays and IgA, IgG and IgM isotypes of rheumatoid factor (RF) in a cohort of patients with early RA in order to assess the value of combining the tests. The serum samples were obtained from 46 RA patients, 80 patients with systemic rheumatic disease, and 20 blood donors. ACPAs were measured using five different commercial kits. The receiver operating characteristic (ROC) curves of the anti-ACPA tests had area under the curve (AUC) values of 0.60-0.83. The diagnostic accuracy of the Bio-Rad multiplex flow immunoassay, a new technology for ACPA testing, was very similar to that of the other widely used commercial immunoassays. The EliA CCP-Phadia test was the most specific, and had the best positive likelihood ratio and positive predictive values, whereas the anti-CCP Inova 3.1 test was the most sensitive, and had the best negative likelihood ratio and negative predictive values. The best combination to use for early RA screening was an ACPA test together with IgM and IgA RF. [ABSTRACT FROM AUTHOR]

Background The gene encoding signal transducer and activator of transcription 4 (STAT4) has been reported to be associated with rheumatoid arthritis (RA) in several populations. This work aimed at assessing the association of STAT4 G>T gene polymorphism with the susceptibility, activity and functional disability of RA in Egyptian subjects. Subjects and methods This study included 112 unrelated RA Egyptian patients who were compared to 122 healthy unrelated individuals taken from the same locality. For all subjects, DNA was genotyped for STAT4 G>T (rs7574865) polymorphism using the PCR-RFLP technique. Antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). Results Cases showed a significantly higher frequency of the STAT4 T allele carriage (GT+TT genotypes) compared to controls (51.8% vs. 31.1%, OR=2.37, 95% CI=1.39-4.05, p=0.001). Also the frequency of the STAT4 T allele was significantly higher among cases compared to controls (30.4% vs. 16.8%, OR=2.16, 95% CI=1.39-3.35, p=0.001). Cases positive to the STAT4 T allele (GT+TT genotypes) showed no significant difference compared to those with the GG genotype regarding their clinical and immune parameters. Nonetheless, they showed a more functional disability presented in their significantly higher health assessment questionnaire (HAQ) score (p=0.02). Conclusions This study gives an extra evidence to the association of the STAT4 T allele with the susceptibility and functional disability of RA. [ABSTRACT FROM AUTHOR]

Background Early appearance of antibodies specific for native human type II collagen (anti-CII) characterizes an early inflammatory and destructive phenotype in adults with rheumatoid arthritis (RA). The objective of this study was to investigate the occurrence of anti-CII, IgM RF, IgA RF and anti-CCP in serum samples obtained early after diagnosis, and to relate the occurrence of autoantibodies to outcome after eight years of disease in children with juvenile idiopathic arthritis (JIA). Methods The Nordic JIA database prospectively included JIA patients followed for eight years with data on remission and joint damage. From this database, serum samples collected from 192 patients, at a median of four months after disease onset, were analysed for IgG anti-CII, IgM RF, IgA RF and IgG anti-CCP. Joint damage was assessed based on Juvenile Arthritis Damage Index for Articular damage (JADI-A), a validated clinical instrument for joint damage. Results Elevated serum levels of anti-CII occurred in 3.1 %, IgM RF in 3.6 %, IgA RF in 3.1 % and anti-CCP in 2.6 % of the patients. Occurrence of RF and anti-CCP did to some extent overlap, but rarely with anti-CII. The polyarticular and oligoarticular extended categories were overrepresented in patients with two or more autoantibodies. Anti-CII occurred in younger children, usually without overlap with the other autoantibodies and was associated with high levels of C-reactive protein (CRP) early in the disease course. All four autoantibodies were significantly associated with joint damage, but not with active disease at the eight-year follow up. Conclusions Anti-CII, anti-CCP, IgA RF and IgM RF detected early in the disease course predicted joint damage when assessed after eight years of disease. The role of anti-CII in JIA should be further studied. [ABSTRACT FROM AUTHOR]

Background Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The gene encoding protein tyrosine phosphatase non-receptor type 22 (PTPN22) has been reported to be associated with RA in several populations. Objectives This work aimed at assessing the association of PTPN22 +1858 C>T gene polymorphism with the susceptibility, activity and severity of RA in Egyptian subjects. Subjects and methods This study included 112 unrelated RA patients who were compared to 122 healthy unrelated individuals taken from the same locality. For all subjects, DNA was genotyped for PTPN22 +1858 C>T (rs2476601) polymorphism using the PCR-RFLP technique. Antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). Results Cases showed significantly higher PTPN22 +1858 T allele carriage rate (CT+TT genotypes) compared to controls (34.8% vs. 8.2%, OR=5.98, 95% CI=2.81-12.73, p<0.001). Also the frequency of the PTPN22 +1858 T allele was significantly higher among cases compared to controls (18.7% vs. 4.5%, OR=4.89; 95% CI=2.45-9.76, p<0.001). Cases positive to the PTPN22 T allele (CT+TT genotypes) showed no significant difference from those with the CC genotype regarding clinical and immune parameters. Nonetheless, they showed a more functional disability presented in their significantly higher health assessment questionnaire (HAQ) score (p=0.04). Conclusions This study is a confirmatory evidence of the association of the PTPN22 +1858 T allele with susceptibility and functional disability of RA in Egyptian subjects. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disorder of unknown aetiology resulting in inflammation of the synovium, cartilage and bone. The disease has a heterogeneous character, consisting of clinical subsets of anti-citrullinated protein antibody (ACPA)-positive and APCA-negative disease. Although, the pathogenesis of RA is incompletely understood, genetic factors play a vital role in susceptibility to RA as the heritability of RA is between 50 and 60%, with the human leukocyte antigen (HLA) locus accounting for at least 30% of overall genetic risk. Non-HLA genes, i.e. tumour necrosis factor- α ( TNF- α) within the MHC (major histocompatibility complex) have also been investigated for association with RA. Although, some contradictory results have originated from several studies on TNF- α gene, the data published so far indicate the possible existence of TNF- α gene promoter variants that act as markers for disease severity and response to treatment in RA. The correlation of HLA and non-HLA genes within MHC region is apparently interpreted. A considerable number of confirmed associations with RA and other autoimmune disease susceptibility loci including peptidylarginine deiminase type 4 ( PADI4), protein tyrosine phosphatase non-receptor type 22 ( PTPN22), signal transducer and activator of transcription ( STAT4), cluster of differentiation 244 ( CD244) and cytotoxic T lymphocyte-associated antigen 4 ( CTLA4), located outside the MHC have been reported recently. In this review, we aim to give an update on recent progress in RA genetics, the importance of the combination of HLA-DRB1 alleles, non-HLA gene polymorphism, its detection and autoantibodies as susceptibility markers for early RA disease. [ABSTRACT FROM AUTHOR]

In this study we determined the frequency, sensitivity and specificity of anti cyclic citrullinated peptides (anti-CCP) IgG antibody, total rheumatoid factor (RF-T), and RF isotypes in Iranian patients with rheumatoid arthritis (RA) and their association with age, clinical and serological parameters. Anti-CCP and RF-T and RF isotypes level were measured in 418 patients and 399 healthy controls by enzyme-linked immunosurbant assay (ELISA). Additionally, serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), visual analog scale (VAS) and disease activity score (DAS28) were evaluated in RA patients. The anti-CCP was positive in 53.1% of RA patients and 4.7% of controls. The frequency of RF-T was 61.87% and 17.66% in RA patients and controls respectively. The prevalence of RF isotypes in RA patients was 46.52% for RF-IgM, 23.47% for RF-IgA and 21.74% for RF-IgG. 31.39% of RA patients were RF-IgM positive without RF-IgA and RF-IgG and 21.9% were positive for all three RF classes. The anti-CCP positive patients showed increased number of swollen joints. On the other hand, RF-T positive patients exhibited a longer disease duration, lower age of onset and also higher ESR, CRP level and increased swollen joints. RF-T titer was significantly higher in RA patients with active disease compared to remission, low and moderate active groups. The sensitivity and specificity were 53.1, 95.3 for anti-CCP antibody and 61.8, 82.3 for RF-T. Our results support that anti-CCP and RF titer maybe valuable in estimation of disease activity and other inflammatory parameters in RA patients. [ABSTRACT FROM AUTHOR]

Highlights: [•] We tested anti-CCP for 286 sera of Korean patients and healthy controls by an parylene-A coated plate developed in our laboratory. [•] The anti-CCP ELISA results of RA patients showed 62% sensitivity and 94% specificity, when OA patients were considered as negative controls. [•] This anti-CCP assay was specific like Rheumatoid factor-Immunoglobulin M (gold standard), but lacking sensitivity. [•] The young subjects showed lower concentration of anti-CCP than old subjects in healthy controls. This means that the citrullination is occurring during aging process in healthy controls. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis an inflammatory bowel disease (IBD) and chronically idiopathic immune related that associates with extraintestinal manifestations such as arthritis. Despite of the highly specificity of anti-cyclic citrullinated peptide (CCP) antibodies for rheumatoid arthritis, their role in IBD remains unclear. There are only a few studies on the prevalence of anti-CCP antibodies in patients with IBD. This study aimed to assess the prevalence of anti- CCP antibodies in ulcerative colitis and to investigate possible associations with their clinical and laboratory characteristics. Methods: In this cross-sectional study, 93 consecutive patients with ulcerative colitis referred to gastroenterology clinics in Razi referral hospital of Rasht, Iran, from September 2010 to September 2011. Rheumatologic examination, demographic data and clinical presentation of patients were recorded on specially prepared data sheets. Blood sample was collected for assessment of anti-CCP and other laboratory tests. Data were analyzed by the Chi square test, Fisher Exact test and student t test, using the SPSS 20 software for Windows, and P value less than 0.05 was considered significant. Results: Of 93 patients, anti-CCP antibodies detected in 10.8% of cases (CI 95%: 4.5-17.1%). There were a significant relation between the prevalence of anti CCP positivity and aphthous ulcers and ocular manifestations whereas other parameters were not significantly related. Conclusion: Anti CCP may have a possible role in some ulcerative colitis manifestations but there was no association between the presence of these antibodies and activity or extension of inflammatory colitis. We suggest other studies especially molecular studies to investigate other aspects of these antibodies in IBD patients [ABSTRACT FROM AUTHOR]

Introduction The anti-cyclic citrullinated peptide (anti-CCP) enzyme-linked immunosorbent assay has a high sensitivity and specificity for rheumatoid arthritis (RA). It has been used in especially early diagnosis of RA, and used to discriminate from other forms of arthritis. Anti-CCP positivity is unknown in brucellosis presented with peripheric arthritis (BPA), like other rheumatic diseases. The objective of this study was to investigate the positivity of anti-CCP in patients with BPA in contrast to the patients with RA and healthy controls. Additionally, we have aimed to monitor changes of anti-CCP levels following the brucellosis treatment. Methods The study group consisted of 137 subjects. 62 brucellosis patients presented with peripheric arthritis. Additionally, 33 RA patients and 42 healthy subjects selected as control groups. The anti-CCP, rheumatoid factor and anti-nuclear antibody levels of the subjects were measured. Results Concerning the 62 BPA, 20 % (13 patients) of them had elevated anti-CCP levels. On the other side, of the 33 RA patients, 78.78 % (26 patients) of them had increased anti-CCP levels. Only one healthy subject's anti-CCP level was positive. There was statistically significant difference among the groups. After brucellosis treatment, monitorisation of the 13 patients with BPA who have the positive anti-CCP levels, were challengingly interesting because none of the patients had positive anti-CCP levels. Conclusions Anti-CCP may be positive marker in the diagnosis of BPA but clinicians need to be careful during the follow up period because it may turn into normal ranges. Additionally, patients presented with peripheric arthritis and anti-CCP positivity need to be evaluated also for the differential diagnosis of BPA. [ABSTRACT FROM AUTHOR]

pulmonary involvement in rheumatoid arthritis (RA) frequently occurs after arthritis, and arthritis after pulmonary involvement is rare. A 46-year-old-man complained about left side chest and joint pain. He had bilateral pleural effusion in chest radiology, and anaemia, high serum c-reactive protein and erythrocyte sedimentation rate in laboratory assessment. pleural effusion sampling was compatible with exude, and included low glucose and pH, high adenosine deaminase and cholesterol, and lymphocyte dominance. RA and pleural involvement was diagnosed by excluding other causes of bilateral pleural effusion, and positivity to rheumatoid factor and anticyclic citrullinated peptide (anti-CCp) of serum. Chest pain and pleural effusion was recovered after treatment with anti-inflammatory drugs (hydroxychloroquine sulfate, methotrexate, methylprednisolone) in follow-ups. This case reminds us that RA should be kept in mind in the differentiation of bilateral pleural effusion even in the absence of a known RA diagnose. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an inflammatory multisystem disease of unknown etiology characterized by chronic destructive synovitis. It's prevalence is about 1% all over the world. Serologic markers are also important beside some clinical situations upon RA diagnosis. Today, the most commonly used laboratory test is rheumatoid factor (RF) in patients with suspected RA. RF is sensitive but not a specific biomarker for diagnosing RA. Early diagnosis of RA is essential to prevent of progressive joint damage. In recent years, anticyclic citrullinated peptide/protein antibody (anti-CCP) attracts the attention as a remarkable biomarker for early diagnosis. Anti-CCP which is a family of anti-citrullinated protein antibodies (ACPA) family, showed quite satisfactory specificity in the diagnosis of RA. Due to the prescence of ACPA was included to 2010 RA diagnostic criteria, in a manner of speaking, importance of anti-CCP was registered. [ABSTRACT FROM AUTHOR]

Anti-citrullinated protein/peptide antibodies (ACPA) are the principal autoantibody system associated with rheumatoid arthritis (RA), with diagnostic sensitivity of 70% and specificity of 95%. Current testing for ACPA uses the anti-cyclic citrullinated peptide assay (anti-CCP) which measures a generalized reactivity with citrulline-containing peptides, thus giving no insight into reactivity to specific RA antigens. Of these, the best characterized are, α-enolase, fibrinogen/fibrin, vimentin, Type 2 collagen and filaggrin, antibodies to each of which are found in approximately 30-60% of RA cases. Given reports of cross-reactivity between citrullinated antigens, we discuss whether or not measuring these specific antibodies could aid: clinical diagnosis, identification of clinical subsets and drug responses, or provide insight into pathogenic mechanisms or etiology of RA. [ABSTRACT FROM AUTHOR]

Recently, it has been found that some lupus patients may have anti-cyclic citrullinated peptide antibodies (anti-CCP), although the clinical significance of such finding is not well established. Systemic lupus erythematosus (SLE) patients may have joint complaints that are very similar to those observed in rheumatoid arthritis (RA). In early stages of disease, this form of arthritis can be difficult to differentiate from RA, so it is not rare that some SLE patients are initially misdiagnosed to have this disease. This study aims to investigate the prevalence of anti-CCP in SLE patients from Southern Brazil and its association with clinical and serological profiles. One hundred nine SLE patients were studied for anti-CCP and compared with data of 156 RA patients and 100 healthy volunteers. Comparison of clinical and autoantibody profile of anti-CCP-positive and anti-CCP-negative SLE patients was done. All SLE patients positive of anti-CCP were submitted to hand and feet X-rays. Anti-CCP was positive in 15 of 109 SLE patients, and one of them had confirmed the diagnosis of rhupus. This prevalence was significantly higher than in healthy controls ( p = 0.0004) and lower than in RA patients ( p < 0.0001). No relationship could be found with clinical profile, including joint complaints. SLE patients with anti-CCP had higher prevalence of anti-Ro ( p = 0.02) and anti-La ( p = 0.004) autoantibodies, in comparison with those negative to anti-CCP. We found that 13.7 % of Brazilian patients with SLE have positive anti-CCP. Patients with anti-CCP showed higher prevalence of anti-Ro and anti-La autoantibodies than those negative for anti-CCP. Only a careful and prolonged follow-up will reveal the real clinical value of these markers in each patient individually. [ABSTRACT FROM AUTHOR]

Anti-citrullinated protein/peptide antibodies (ACPAs) have recently been identified as sensitive and specific diagnostic and prognostic markers in rheumatoid arthritis (RA). In this study, we wished to assess the diagnostic performance of the third-generation anti-CCP3.1 assay, but with special focus on the rheumatoid factor (RF)-negative RA population. Anti-CCP as well as anti-MCV was tested in 119 RA patients and 118 control patients using second and third-generation assays. Using these optimal cut-off levels, the diagnostic sensitivity of anti-CCP2, CCP3, and CCP3.1 was 74.8, 78.8, and 83.0 %, respectively, while the specificity was 95.7, 96.6, and 98.3 %, respectively. The diagnostic performance of the CCP3.1 test was significantly better than that of CCP2 ( p = 0.041). In addition, the CCP3.1 test performed significantly better than the MCV test as well ( p = 0.0003). When the diagnostic performance of the CCP3.1, CCP2, and MCV tests was compared in the 35 RF-negative patients, the CCP3.1 test exerted significantly better performance than the MCV test ( p = 0.006), and it also showed a tendency of better performance in comparison with the CCP2 test ( p = 0.131). In conclusion, the CCP3.1 assay can significantly increase the sensitivity of ACPA testing in RF-negative RA, as well as in the total RA population. [ABSTRACT FROM AUTHOR]

Objectives: Anti-cyclic citrullinated peptide (CCP) antibody has recently been used in the classification of rheumatoid arthritis (RA). This antibody is more specific than rheumatoid factor (RF) for the diagnosis of RA. The study objectives were to determine the sensitivity, specificity, positive and negative predictive values of anti-CCP in RA diagnosis. Methodology: Eighty RA patients and 80 non-RA individuals were included in the study. Blood was collected from both arms of study subjects and tested for anti-CCP and RF antibodies. Relevant clinical information and laboratory profiles of the RA patients were evaluated using patients' medical records and Integrated Laboratory Management System (ILMS), respectively. Results: The sensitivity and specificity of anti-CCP were 35% and 100% respectively. The positive and negative predictive values were 100% and 61%, respectively. Positive anti-CCP was found significantly associated with multiple joint pain (p < 0.001) and hand's joints pain (p=0.01), symmetrical joints involvement (p=0.015) and high CRP value (p < 0.001). Anti-CCP was also found to have positive association with RF (p < 0.001). Conclusion: Anti-CCP is highly specific for the diagnosis of RA. High positive predictive value should be taken into consideration for effective treatment. [ABSTRACT FROM AUTHOR]

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Objective: Patients with chronic hepatitis C virus (HCV) infection may show a variety of rheumatic symptoms and signs. Anti-cyclic citrullinated peptide (anti-CCP) is widely used as as a marker, particularly for rheumatoid arthritis (RA), and may be positive in some diseases that also cause arthritis, such as systemic lupus erythematosus, familial Mediterranean fever, Behcet's disease, and psoriatic arthritis. Materials and Methods: Blood samples were obtained (in routine protocols) from 57 patients with chronic HCV infection from the Gastroenterology Clinic of Ataturk University and Infectious Disease Clinic of Erzurum Region Research and Education Hospital. Normal sera were obtained from volunteer blood donors at Ataturk University. Results: Anti-CCP antibodies were found in 5 chronic HCV patients with RA. The patient with the highest anti-CCP antibody level had RA. No patient in the control group was positive for anti-CCP antibodies. Conclusion: Anti-cyclic citrullinated peptide (anti-CCP) antibodies should be measured frequently in patients with HCV and an additional systemic disease, such as end-stage chronic renal failure, chronic obstructive airway disease, and decompensated liver cirrhosis, to differentiate RA from non-RA arthropathy. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate the associations between human leukocyte antigen (HLA)-DRB1 alleles with genetic susceptibility to rheumatoid arthritis (RA) and production of antibodies against cyclic citrullinated peptide (anti-CCP antibody) and rheumatoid factor (RF) in Turkish RA patients. Methods: We studied 291 RA patients and 253 controls. Genotyping was performed by polymerase chain reaction with sequence-specific oligonucleotide probes hybridization method. Serum levels of anti-CCP antibody, IgM-RF and high sensitive C-reactive protein titers were measured by commercial kits using immunological methods. Results: We found that HLA-DRB1*04 and *09 alleles were associated in anti-CCP+ and anti-CCP+ RA patients ( P < 0.0001 and P < 0.001, respectively), while DRB1*01 and *04 were determined to be higher in RF+ RA patients ( P < 0.001 and P < 0.0001, respectively). Moreover, DRB1*11 and DRB1*13 alleles were determined to be lower in RF and anti-CCP/RF+ RA patients ( P < 0.001 for both). HLA-DRB1*04 was identified as a common responsible allele for susceptibility to the disease in anti-CCP, RF and anti-CCP/RF− RA patients ( P = 0.0018, P = 0.0004 and P = 0.0023, respectively). HLA-DRB1*13 allele alone was found to be protective against to anti-CCP+ and RF− RA ( P = 0.0003 and P = 0.006, respectively). On the contrary, there was no protective allele in anti-CCP/RF− RA as well as anti-CCP− RA patients. Conclusion: This study indicates that associate and protective HLA-DRB1 allele distributions are different in autoantibody (anti-CCP or RF or anti-CCP/RF)+ RA and autoantibody− RA patients, with exceptions of DRB1*04 and DRB1*13. [ABSTRACT FROM AUTHOR]

Autoantibodies in early rheumatoid arthritis (RA) have important diagnostic value. The association between the presence of autoantibodies against cyclic citrullinated peptide and the response to treatment is controversial. To prospectively evaluate a cohort of patients with early rheumatoid arthritis (<12 months of symptoms) in order to determine the association between serological markers (rheumatoid factor (RF), anti-citrullinated protein antibodies) such as anti-cyclic citrullinated peptide antibodies (anti-CCP) and citrullinated anti-vimentin (anti-Sa) with the occurrence of clinical remission, forty patients diagnosed with early RA at the time of diagnosis were evaluated and followed for 3 years, in use of standardized therapeutic treatment. Demographic and clinical data were recorded, disease activity score 28 (DAS 28), as well as serology tests (ELISA) for RF (IgM, IgG, and IgA), anti-CCP (CCP2, CCP3, and CCP3.1) and anti-Sa in the initial evaluation and at 3, 6, 12, 18, 24, and 36 months of follow-up. The outcome evaluated was the percentage of patients with clinical remission, which was defined by DAS 28 lower than 2.6. Comparisons were made through the Student t test, mixed-effects regression analysis, and analysis of variance (significance level of 5%). The mean age was 45 years, and a female predominance was observed (90%). At the time of diagnosis, RF was observed in 50% of cases (RF IgA-42%, RF IgG-30%, and RF IgM-50%), anti-CCP in 50% (no difference between CCP2, CCP3, and CCP3.1) and anti-Sa in 10%. After 3 years, no change in the RF prevalence and anti-CCP was observed, but the anti-Sa increased to 17.5% ( P = 0.001). The percentage of patients in remission, low, moderate, and intense disease activity, according to the DAS 28, was of 0, 0, 7.5, and 92.5% (initial evaluation) and 22.5, 7.5, 32.5, and 37.5% (after 3 years). There were no associations of the presence of autoantibodies in baseline evaluation and in serial analysis with the percentage of clinical remission during follow-up of 3 years The presence of autoantibodies in early RA has no predictive value for clinical remission in early RA. [ABSTRACT FROM AUTHOR]

Articular symptoms are common in SSc and joint pain is a frequent presenting feature of this disease. Hand involvement is often the first clinical manifestation of SSc and could be resulted from fibrosis or synovitis or an overlap syndrome with rheumatoid arthritis (RA); though, the latter is a controversy in practice. To define the clues when identifying the nature of the hand arthropathy in SSc. In order to determine the hand arthropathy, serological tests, hand radiography, finger-to-palm (FTP) distance and other clinical features, disease activity and functional scoring parameters were assessed. Twenty-eight consecutive SSc patients and 43 controls (21 rheumatoid arthritis and 22 healthy controls) were included. Radiographic findings in SSc patients were: Erosions 25%, joint space narrowing 17.9%, arthritis 10.7%, radiological demineralisation 42.9%, acro-osteolysis 25%, flexion contracture 28.6% and calcinosis 17.9%. Anti-CCP antibody and RF positivity were as follows: In SSc group: 3 (11%) and 7 patients (25%); In RA group: 13 (62%) and 19 patients (90.5%); In healthy control group: 1 (4%) and 3 persons (13.6%), respectively. Two patients (7.14%) were regarded as RA overlap, whom both had positive RF and positive anti-CCP results and their radiographs revealed arthritis. Seventeen patients (61%) were regarded as SSc arthropathy; all were negative for RF and anti-CCP but revealed nonarthritic radiological findings. (Among them, only one patient had positive anti-CCP result). The remainder (9 patients) had no radiological or serological finding positive for arthropathy. Arthritis was found to have correlation with heart involvement and FTP was correlated with lung involvement. Hand involvement in SSc is a challenge in rheumatology practice; Radiographic testing when evaluated with RF and anti-CCP will be a helpful tool to discriminate SSc arthropathy from RA-SSc overlap. Hand arthropathy should increase the interest in the serious internal organ involvements of SSc. [ABSTRACT FROM AUTHOR]

Abstract: Sjögren Syndrome (SS) is a systemic, autoimmune disorder characterized by lymphocytic infiltration of the exocrine glands. Different clinical associations have been described for each of the diverse autoantibodies found in SS patients. Antibodies directed against the Ro/La ribonucleoprotein complexes have been correlated with younger age, more severe dysfunction of the exocrine glands and a higher prevalence of extraglandular manifestations. Anti-nuclear antibodies and rheumatoid factors have been associated to extraglandular manifestations and an active immunological profile, while cryoglobulins are markers of more severe disease and correlate to lymphoma development and death. Antibodies to cyclic citrullinated peptides are scarce in SS and have been linked in some cases to the development of non-erosive arthritis. Furthermore, the presence of anti-mitochondrial antibodies and anti-smooth muscle antibodies in the sera of primary SS patients is considered indicative of primary biliary cirrhosis and autoimmune hepatitis, respectively. In addition, anti-centromere antibodies have been associated with a clinical phenotype intermediate between primary SS and systemic sclerosis, while antibodies against carbonic anhydrase have been related to renal tubular acidosis. Finally, an association of anti-muscarinic antibodies with cytopenias and a higher disease activity has also been described in primary SS. In conclusion, although not all of the above mentioned antibodies are useful for predicting distinct patient subgroups in SS, knowledge of the clinical associations of the different autoantibody specificities encountered in SS can advance our understanding of the disease and improve patient management. [Copyright &y& Elsevier]