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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.

Rheumatoid arthritis (RA) is associated with a significant disease burden and high costs for society. Because the disease has identifiable preclinical stages, screening and prevention have become a possibility in RA. Anticitrullinated peptide antibodies (ACPAs) are arguably the most likely candidate biomarker to screen for RA. This paper reviews the evidence for the use of ACPAs as a screening test in the broader general population, to identify individuals at high risk of subsequent onset of RA. We will review the diagnostic properties of the test and its positive and negative predictive value in different settings. We will discuss how ACPA testing could effectively be integrated in a broader screening strategy for RA.

ObjectivesRecent studies suggest that implementation of the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis (RA) leads to higher inflammatory activity in seronegative compared with seropositive patients at time of diagnosis. Our aim was to compare the disease course in seronegative and seropositive patients classified according to the 2010 criteria.MethodsDMARD-naïve patients with RA fulfilling the 2010 criteria were included in the treat-to-target ARCTIC trial and followed for 24 months. We stratified patients as seropositive (rheumatoid factor (RF)+, anticitrullinated protein antibodies (ACPA)+ or both) or seronegative (RF– and ACPA–) and compared disease activity, radiographic progression, treatment response and remission rates across groups.Results230 patients were included with mean (SD) age 51.4 (13.7) years, and 61% were female. 34 patients (15%) were seronegative. At 24 months, disease activity measures, radiographic progression and remission rates were similar between groups, despite more inflammatory activity in seronegative patients at baseline. Treatment response was slower in seronegative compared with seropositive patients. The groups received similar treatment.ConclusionOur findings suggest that among patients with RA classified according to the 2010 ACR/EULAR criteria, seronegative patients respond well to modern treatment strategies. However, treatment response was somewhat slower in seronegative patients and radiographic progression was similar in seronegative and seropositive patients. Our results indicate that seronegative RA is not a mild form of the disease and requires intensive treat-to-target therapy similar to treatment of seropositive RA.

Background: Aggregatibacter actinomycetemcomitans (Aa) is a Gram-negative coccobacillus recognized as a pathogen in periodontitis and infective endocarditis. By producing a toxin (leukotoxin A, LtxA) that triggers global hypercitrullination in neutrophils, Aa has been recently linked to rheumatoid arthritis (RA) pathogenesis. Although mechanistic and clinical association studies implicate Aa infection in the initiation of autoimmunity in RA, direct evidence in humans is lacking. Case: We describe a 59-year-old man with anti-citrullinated protein antibody (ACPA)-positive RA who presented for evaluation of refractory disease. He was found to have Aa endocarditis. Following antibiotic treatment, joint symptoms resolved and ACPAs normalized. Given the implications for RA immunopathogenesis, we further investigated the bacterial, genetic and immune factors that may have contributed to the patient's clinical and autoimmune phenotypes. Methods: DNA was extracted from serum and used to amplify the Aa leukotoxin (tx) promoter region by PCR, which was further analyzed by Sanger sequencing. High-resolution identification of HLA alleles was performed by sequenced based typing (SBT). TNF-alpha, IFN-gamma, GM-CSF, IL-1 beta, IL-6, IL-8, IL-17A, IL-18, IL-21, and IL-22 were quantified in serum by a multiplex immunoassay. IgG and IgA antibodies to Aa LtxA were assayed by ELISA. Results: Aa genotyping confirmed infection with a highly leukotoxic strain carrying a 530-bp /tx promoter deletion, shown to result in 10- to 20-fold higher bacterial expression of LtxA. lmmuno-phenotyping showed high anti LtxA antibodies, elevated cytokines implicated in RA pathogenesis (Th1/Th17), and specific host susceptibility conferred by three HLA alleles strongly linked to ACPAs and RA (DRB1*04:04:04, DRB1*15:01, and DPB1*04:01). One year after eradication of Aa, the patient remained free of arthritis and anti-CCP antibodies. Conclusion: In the context of genetic risk for RA, systemic subacute infection with a leukotoxic strain of Aa can drive ACPA production and a clinical phenotype similar to RA.

ObjectivesTo evaluate efficacy and safety of abatacept+methotrexate (MTX) in biologic-naive, anticitrullinated protein antibody (ACPA)-positive Japanese patients with active rheumatoid arthritis (RA) and early erosion versus placebo+MTX.MethodsIn this phase IV, multicentre, double-blind study (NCT01758198), patients were randomised (1:1) to receive intravenous abatacept (~10 mg/kg) or placebo, plus MTX (≥6 mg/week). Primary efficacy objectives were to compare American College of Rheumatology 20 (ACR20) response rates at week 16 and mean change from baseline in van der Heijde-modified total Sharp score (vdH-mTSS) at week 24 between abatacept+MTX and placebo+MTX groups.ResultsOverall, 203 and 202 patients received abatacept+MTX and placebo+MTX, respectively. At week 16, ACR20 response rates were higher in the abatacept (75.4%) versus placebo group (27.7%; pConclusionsCompared with MTX alone, abatacept+MTX improved clinical symptoms and inhibited structural damage progression in ACPA-positive, Japanese patients with RA, early erosion and inadequate response to MTX.

Objectives: The development of RA includes a phase of arthralgia preceding clinical arthritis. The aetiology of symptoms of arthralgia is unclear. Since subclinical joint inflammation is expected to be causally related to pain, we aimed to study associations between subclinical MRI-detected inflammation and pain in patients with arthralgia suspicious for progression to RA. Methods: Unilateral MRIs of the wrist, MCP (2-5) and MTP (1-5) joints of 325 patients who fulfilled the EULAR definition of arthralgia suspicious for progression to RA were scored by two readers on subclinical inflammation (synovitis, bone marrow oedema and tenosynovitis). Associations between MRI-detected inflammation and overall pain severity at patient level (measured using the visual analogue scale), as well as with local joint tenderness, were studied. Analyses were stratified for ACPA. Results: At patient level, synovitis (β = 0.10, P = 0.048) and tenosynovitis (β = 0.11, P = 0.026) associated with the visual analogue scale pain. Of the 1620 imaged joints, 447 (28%) were tender. MRI-detected synovitis associated independently with joint tenderness in all patients (odds ratio 1.74, P < 0.001), and in the ACPA-negative stratum (odds ratio 1.96, P < 0.001). In the ACPA-positive stratum only bone marrow oedema (osteitis) was independently associated with tenderness (odds ratio 2.39, P = 0.005). Sensitivity analyses in patients who developed inflammatory arthritis during follow-up (n = 61) revealed similar associations. Subclinical inflammation was present in 51% of tender joints and 39% of non-tender joints. Conclusion: In patients with arthralgia suspicious for progression to RA, MRI-detected subclinical inflammation is associated with overall pain and local joint tenderness. However, the association is partial, indicating that subclinical inflammation is not the sole explanation of the arthralgia.

Aims: To reveal the prevalence of diabetes mellitus (DM) in patients with newly diagnosed rheumatoid arthritis (RA) and evaluate the association between cli nical cha - racteristics of RA and DM, as well as, treatment response in newly diagnosed RA patients with DM. Methods: Newly diagnosed, adult, RA patients, who were registered in Danish Danbio since 1st January 2010, were included. Patients' demographics, serology results including rheumatoid factor (RF), anti-cyclic citrullina - ted peptide antibody (anti-CCP) and antinuclear antibo - dy (ANA), as well as, disease activity score in 28 joints- -C-reactive protein (DAS28-CRP), at the time of diagnosis and after 4 months (±1-2 months) of treatment initiation, were extracted from Danbio Regis try. To reveal the presence of DM, patients' electronic medi cal records were reviewed. The prevalence of DM in our patients was compared (using an age- and gender-matched analysis) with that expected from Danish popu lation. Results: of 439 included patients, 60.1% were female, mean of age 64.6±15.0 years and RA disease duration 2.6±1.7 years. Prevalence of DM was 57/439 (12.9%), herein type II DM 52 (91.2%) and type I DM 5 (8.8%). Except for two patients, diagnosis of DM was esta - blished prior to the diagnosis of RA. The prevalence of DM in newly diagnosed RA patients of all ages was signi ficantly increased versus that expected from Da - nish population (RR=2.21, CI=1.40-3.42, P < 0.001). In addition, prevalence of DM was significantly increa - sed with more than twice of the expected for RA patients aged 65-84. Both genders showed increased risk of DM after subgroup analysis. The presence of DM in RA patients was significantly associated with age (P < 0.001) and RA disease duration ≥4 years (P =0.05). We did not find any significant associations between presence of DM and gender, RF, anti-CCP, as well as, ANA. Additionally, presence of DM in the RA patients was not a negative predictor of treatment response measured by the European League Against Rheumatism (EULAR) response criteria and DDAS28-CRP. Conclusion: Newly diagnosed RA patients are at hi gher risk of DM (13% versus 5.7% in Denmark), and a high index of suspicion must be kept.

To determine the prevalence of thyroid disorders among newly diagnosed rheumatoid arthritis (RA) patients and evaluate the association between clinical characteristics of RA and thyroid disorders, and also initial treatment response in the RA patients with thyroid disorders. Newly diagnosed, adult RA patients who were diagnosed according to the new 2010 American College of Rheumatology/European League Against Rheumatism criteria since January 1, 2010, were included. Patients’ demographic data, serology results including immunoglobulin M rheumatoid factor (IgM RF), anticyclic citrullinated peptide antibody (anti-CCP), and antinuclear antibody (ANA), and also disease activity score in 28 joints-C-reactive protein at the time of diagnosis and after 4 months (±1–2 months) of treatment initiation were extracted from Danish Danbio Registry. Patients’ electronic hospital records for the past 10 years were reviewed to reveal if they had been diagnosed with thyroid disorders or they had abnormal thyroid test. In all, 439 patients were included, female 60.1%, mean age 64.6 ± 15.0 years and disease duration 2.6 ± 1.7 years. Prevalence of thyroid disorders was 69/439 (15.7%) and hypothyroidism was the most frequent disorder (30.4%). The presence of thyroid disorders among RA patients was significantly associated with female sex (P

Background Infection by common viruses has long been discussed in the aetiology of a number of autoimmune diseases, including rheumatoid arthritis (RA). However, studies investigating this hypothesis in RA show conflicting results. These studies often lack well-matched control populations, and many do not include data on autoantibodies, genetic risk factors and other environmental factors, which are known to contribute to disease only in subgroups of patients. In the present study, we have therefore examined the role of Epstein-Barr virus (EBV), cytomegalovirus (CMV) and parvovirus B19 (B19) in RA aetiology, by analysing anti-viral antibodies in relation to anti-citrullinated protein antibodies (ACPA), smoking, HLA-DRB1 shared epitope (SE) alleles, and clinical parameters, in both RA patients and matched controls. Methods Anti-viral antibodies were measured by ELISA in serum samples from 990 RA patients and 700 controls from the Swedish population-based Epidemiological Investigation of RA (EIRA) cohort. Data on ACPA, smoking, SE, inflammation (C-reactive protein) and disease activity score in 28 joints (DAS28) was obtained from the EIRA database. Fisher’s exact test, the chi-squared test, and the Mann-Whitney U test were used to calculate differences in anti-viral antibody frequencies and levels; unconditional logistic regression was used to determine the association of anti-viral antibodies with different RA subsets. Results Antibodies against all viruses were highly prevalent in EIRA, with no major differences detected between ACPA-positive RA, ACPA-negative RA and controls. However, both anti-B19 and anti-EBV IgG levels were significantly lower in ACPA-positive RA compared to controls, and there were significant interactions between low levels of anti-B19 and anti-EBV antibodies and SE in the development of ACPA-positive RA. Conclusion We could not detect an association between RA and elevated anti-viral antibody levels, for any of the three common viruses, EBV, CMV or B19. On the contrary, our study demonstrated association between low anti-EBV/anti-B19 antibody levels and ACPA-positive RA, in particular when HLA-DRB1 SE was present. These data could potentially suggest that high anti-viral antibody levels would be protective against ACPA-positive RA. Further investigations are required to address the mechanisms behind these findings. Electronic supplementary material The online version of this article (doi:10.1186/s13075-017-1423-9) contains supplementary material, which is available to authorized users.

Antibodies against cyclic citrullinated peptides (anti-CCP), antibodies against double-stranded deoxyribonucleic acid (anti-dsDNA), RF, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), antibodies against nuclear antigens (ANA) tests were performed in blood. A retrospective analysis of RF, anti-CCP, CRP, ESR, anti-dsDNA, ANA tests results in 154 patients clinically suspected of having rheumatoid arthritis and treated in Rheumatology clinic in 2 years period, was done. Results and conclusions were done: men up to 50 years old and women older than 70 years old usually had seropositive RA, men older than 70 years old and women from 50 to 70 years old – seronegative RA; higher than excess rate RF and anti-CCP results are in patients with seropositive rheumatoid arthritis, especially men up to 70 years old; patients up to 50 years old with seropositive rheumatoid arthritis had strong correlation between RF and anti-CCP tests results; all laboratory tests results were higher in patients with radiological joint damage and who had streptococcal infections in the past.

OBJECTIVE To investigate the inhibitory effect of β-D-mannuronic acid (M2000) on anti-cyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF), antidouble strand DNA (anti-dsDNA) and acute phase reactants in rheumatoid arthritis (RA) patients. METHODS The study included 40 patients with RA who had an inadequate response to conventional therapy (identifier: IRCT2014011213739N2). The patients were permitted to continue the conventional therapy excluding NSAIDs. 21 of them were treated orally by M2000 at a dose of 500 mg twice daily for 12 weeks and the others did not. Serum samples were collected at baseline, 4 weeks and 12 weeks after treatment and were tested for the serum level of anti-CCP and anti-dsDNA antibodies using enzyme linked immunosorbent assay. The serum level of RF and C-reactive proteins (CRP) was determined by the immunoturbidimetric assay, respectively. RESULTS At baseline, all patients in the M2000 treated group and the control group were positive for anti-CCP, RF. moreover, 4 of 21 (19%) in the M2000 treated group and 2 of the 19 (10.5%) patients in the control group were positive for anti-dsDNA antibodies, respectively. The serum levels of anti-CCP, RF and anti-dsDNA were decreased significantly after M2000 therapy (p

Antiphospholipid antibodies (aPLs) are a heterogeneous group of autoantibodies essential for the diagnosis of antiphospholipid syndrome (APS) but do not predict clinical manifestations or disease progression. Hence, the co-presence of other antibodies may prove useful. Autoimmunity directed toward vimentin and other citrullinated peptides was established in rheumatoid arthritis (RA) and in other autoimmune conditions including systemic lupus erythematosus (SLE). We have previously described the presence of autoantibodies directed against vimentin/cardiolipin complex in patients with antiphospholipid syndrome (APS), but there are no data on the role of citrullinated vimentin in APS. Thus, we evaluated the prevalence and clinical significance of anti-MCV in APS patients. The study group consisted of 79 unselected outpatients with APS. Control groups included 25 patients with SLE, 30 patients with RA, and 20 healthy subjects age- and sex-matched. To detect anti-MCV, anti-vimentin, anti-vimentin/cardiolipin, and anti-CCP2 antibodies, commercial or homemade enzyme-linked immunosorbent assays (ELISA) were performed. Anti-MCV antibodies were found in a high percentage of APS patients (26.6%). A significant correlation between anti-MCV and anti-vimentin/cardiolipin serum levels was observed (p = 0.029). Moreover, vimentin reactivity was increased by its citrullination or conjugation with cardiolipin (p = 0.01 and p

Rheumatoid arthritis (RA) is an inflammatory multisystem disease of unknown etiology characterized by chronic destructive synovitis. It and #8217;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. [TAF Prev Med Bull 2014; 13(1.000): 83-88]

The objective of this study was to study genetic factors that influence quantitative anticyclic citrullinated peptide (anti-CCP) antibody levels in RA patients. We carried out a genome-wide association study (GWAS) meta-analysis using 1975 anti-CCP+ RA patients from three large cohorts, the Brigham Rheumatoid Arthritis Sequential Study (BRASS), North American Rheumatoid Arthritis Consortium (NARAC) and the Epidemiological Investigation of RA (EIRA). We also carried out a genome-wide complex trait analysis (GCTA) to estimate the heritability of anti-CCP levels. GWAS-meta-analysis showed that anti-CCP levels were most strongly associated with the human leukocyte antigen (HLA) region with a P-value of 2 × 10(-11) for rs1980493. There were 112 SNPs in this region that exceeded the genome-wide significance threshold of 5 × 10(-8), and all were in linkage disequilibrium (LD) with the HLA- DRB1*03 allele with LD r(2) in the range of 0.25-0.88. Suggestive novel associations outside of the HLA region were also observed for rs8063248 (near the GP2 gene) with a P-value of 3 × 10(-7). None of the known RA risk alleles (∼52 loci) were associated with anti-CCP level. Heritability analysis estimated that 44% of anti-CCP variation was attributable to genetic factors captured by GWAS variants. In summary, anti-CCP level is a heritable trait, and HLA-DR3 and GP2 are associated with lower anti-CCP levels.

BACKGROUND: Articular manifestations are common in systemic lupus erythematosus (SLE) whereas erosive disease is not. Antibodies to cyclic citrullinated peptide (anti-CCP) are citrulline-dependent in rheumatoid arthritis (RA), whereas the opposite is suggested in SLE, as reactivity with cyclic arginine peptide (CAP) is typically present. Antibodies targeting carbamylated proteins (anti-CarP) may occur in anti-CCP/rheumatoid factor (RF)-negative cases long before clinical onset of RA. We analysed these antibody specificities in sera from European patients with SLE in relation to phenotypes, smoking habits and imaging data. METHODS: Cases of SLE (n = 441) from Linköping, Sweden, and Leiden, the Netherlands, were classified according to American College of Rheumatology (ACR) and/or Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) criteria. IgG anti-CCP, anti-CAP and anti-CarP were analysed by immunoassays. Radiographic data from 102 Swedish patients were available. RESULTS: There were 16 Linköping (6.8%) and 11 Leiden patients (5.4%) who were anti-CCP-positive, of whom approximately one third were citrulline-dependent: 40/441 (9.1%) were anti-CarP-positive, and 33% of the anti-CarP-positive patients were identified as anti-CCP-positive. No associations were found comparing anti-CCP or anti-CarP with ACR-defined phenotypes, immunologic abnormalities or smoking habits. Radiographically confirmed erosions were found in 10 patients, and were significantly associated with anti-CCP, anti-CarP and RF. Musculoskeletal ultrasonography scores were higher in anti-CCP-positive compared to anti-CCP-negative patients. CONCLUSIONS: In the hitherto largest anti-CarP study in SLE, we demonstrate that anti-CarP is more prevalent than anti-CCP and that the overlap is limited. We obtained some evidence that both autoantibodies seem to be associated with erosivity. Similar pathogenetic mechanisms to those seen in RA may be relevant in a subgroup of SLE cases with a phenotype dominated by arthritis. Funding agencies: County Council of Ostergotland; Swedish Society for Medical Research; Swedish Rheumatism Association; Swedish Society of Medicine; Professor Nanna Svartz foundation; King Gustaf V 80-year foundation; Dutch Arthritis Foundation; IMI JU project, BeTheCure [

ObjectivesTofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). We examined response to tofacitinib 5 or 10 mg two times a day in patients with seropositive vs seronegative RA.MethodsData were pooled from five Phase III studies of conventional synthetic disease-modifying antirheumatic drug (csDMARD)- or biological DMARD-inadequate responders (ORAL Step [NCT00960440]; ORAL Scan [NCT00847613]; ORAL Solo [NCT00814307]; ORAL Sync [NCT00856544]; ORAL Standard [NCT00853385]). ‘Serotype’ subgroups were: anticyclic citrullinated peptide (CCP) and rheumatoid factor (RF) positive (anti-CCP+/RF+); anti-CCP+/RF negative (-); anti-CCP-/RF+; anti-CCP-/RF-. At month 3, ACR20/50/70 response rates, Disease Activity Score (DAS28-4[ESR])-defined remission (DAS28-4[ESR]ResultsBaseline demographics/characteristics were similar across subgroups. Tofacitinib significantly improved ACR20/50/70 response rates, DAS28-4(ESR) LDA rates and CFB in HAQ-DI and FACIT-F vs placebo across subgroups. More anti-CCP+/RF+ than anti-CCP-/RF- patients had ACR20/50/70 responses (ACR20/50: both tofacitinib doses; ACR70: 10 mg two times a day). SF-36 physical functioning improved in anti-CCP+/RF+, anti-CCP+/RF- and anti-CCP-/RF+ patients (both tofacitinib doses) and anti-CCP-/RF- patients (10 mg two times a day) vs placebo. More anti-CCP+/RF+ and anti-CCP+/RF- than anti-CCP-/RF- patients achieved DAS28-4(ESR) remission and LDA with tofacitinib 10 mg two times a day. Frequency of adverse events (AEs), serious AEs and discontinuations due to AEs were similar across subgroups.ConclusionGenerally, tofacitinib efficacy (ACR20/50/70 responses) and safety were similar across subgroups. DAS28-4(ESR) remission rates and SF-36 physical functioning appeared lower in anti-CCP- patients.

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, Behçet's disease, and psoriatic arthritis.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.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.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.Kronik hepatit C virüs (HCV) enfeksiyonu çeşitli romatolojik belirti ve semptomlarla seyredebilir. Anti-siklik sitrüllenmiş peptid (Anti-CCP) özellikle romatoid artrit (RA) tanısında yaygın şekilde kullanılan, ayrıca sistemik lupus eritematozus, ailevi akdeniz ateşi ve psöriatik artrit gibi artritle birlikte seyreden bazı hastalıklarda da pozitif olduğu gösterilmiş bir antikordur.Çalışmada Atatürk Üniversitesi Gastroenteroloji Kliniği ve Erzurum Bölge Eğitim ve Araştırma Hastanesi Enfeksiyon Hastalıkları Kliniği’nden 57 kronik HCV enfeksiyonlu hastadan rutin tetkikleri sırasında alınmış olan kanlar kullanıldı. Kontrol kanları Atatürk Üniversitesi kan vericilerinden artan kanlardan toplandı.Kronik HCV enfeksiyonuna ilaveten RA tanısı da almış olan 5 hastanın tamamında Anti-CCP pozitif bulundu. Anti-CCP seviyesi en yüksek olan hasta da RA’i olan bir hasta idi. Kontrol grubundaki hastalardan hiçbirinde Anti-CCP pozitif değildi.Kronik HCV’li hastalarda kronik böbrek yetmezliği, kronik obstriktif akciğer hastalığı veya dekompanse karaciğer sirozu gibi sistemik hastalıkların varlığında, Anti-CCP daha sık olarak görülebilmektedir. Ayrıca Anti-CCP pozitifliğinin, bu hasta grubunda RA ile non-RA artropati ayrımında da kullanılabileceği düşünülmektedir.

International audience; Objective: To investigate whether subfamilies of the RA-specific autoantibodies to human citrullinated fibrinogen (AhFibA) differentially associate with the RA risk factors, HLA-DRB1 shared epitope containing alleles (SE alleles) and cigarette smoking, and thus help to predict the disease outcome. Methods: AhFibA and their anti-α36-50Cit and anti-β60-74Cit subfamilies were assayed by ELISA, at baseline, in the French ESPOIR (Etude et Suivi des Polyarthrites Indifférenciées Récentes) cohort composed of undifferentiated arthritides and RA patients of < 6 months' duration. Cigarette smoking, SE alleles' presence, DAS28, HAQ and modified Sharp-van der Heijde Score data were obtained at baseline, and after follow-up. Results: After 3 years, 701 patients were classified as having RA according to the ACR/EULAR 2010 criteria. Among them, 349 (50%), 203 (29%) and 257 (37%) were AhFibA-, anti-α36-50Cit- and anti-β60-74Cit-positive, respectively. The presence and titres of AhFibA and their subfamilies similarly associated with SE alleles, irrespective of their fine specificity, without significant effect of smoking. Neither their presence nor their titre was associated with DAS28 or HAQ. The presence of at least one subfamily was associated with a faster Sharp/van der Heijde score progression, albeit without correlation with the titre. Conclusion: AhFibA and their main subfamilies are similarly associated with SE alleles without additional effect of smoking. Whatever their fine specificity was, their presence (but not their titre) similarly constituted a marker of faster joint destruction.

Anti-citrullinated protein autoantibodies (ACPAs) are the major autoantibodies in rheumatoid arthritis (RA). Anti-citrullinated protein autoantibodies are directed against different citrullinated antigens, including filaggrin, fibrinogen, vimentin, and collagen. Presence of ACPA is associated with joint damage and extra-articular manifestations, suggesting that ACPAs are most likely pathogenic autoantibodies in RA. In vitro, ACPAs induce macrophage tumor necrosis factor alpha (TNF-α) production, osteoclastogenesis, and complement activation. These autoantibodies also induce the formation of neutrophil extracellular traps (NETs). Additionally, ACPAs induce pathogenic cytokines expression and oxidative stress in immune cells derived from RA patients. The aim of this review is to show the pathogenic roles of these autoantibodies in RA.

Presence of autoantibodies precedes development of seropositive rheumatoid arthritis (SP RA) and seropositive arthralgia patients (SAP) are at risk of developing RA. The aims of the study are to identify additional serum immune markers discriminating between SP and seronegative (SN) RA, and markers identifying high-risk SAP. Sera from SAP (n = 27), SP RA (n = 22), SN RA (n = 11) and healthy controls (n = 20) were analyzed using the Human Cytokine 25-Plex Panel. Selected markers were validated in independent cohorts of SP RA (n = 35) and SN RA (n = 12) patients. Eleven of 27 SAP developed RA within 8 months (median follow-up time, range 1–32 months), and their baseline serum markers were compared to 16 non-progressing SAP. SAP and SP RA patients showed a marked overlap in their systemic immune profiles, while SN RA showed a distinct immune profile. Three of 4 markers discriminating between SP and SN RA (IL-1β, IL-15 and Eotaxin, but not CCL5) were similarly modulated in independent cohorts. SAP progressing to RA showed trends for increases in IL-5, MIP-1β, IL-1RA and IL-12 compared to non-progressing SAP. ROC analysis showed that serum IL-5 most accurately discriminated between the two SAP groups (AUC > 0.8), suggesting that baseline IL-5 levels may aid the identification of high-risk SAP.

مقدمه: آرتریت روماتویید یک بیماری التهابی مزمن مفصلی است که با وجود بعضی از آنتی‌بادی‌ها مشخص می‌شود. Anti-CCP (Anti-cyclic citrullinated protein antibodies) یکی از بهترین روش‌ها برای تشخیص آنتی‌بادی‌های ضد فیلاگرین می‌باشد. در این مطالعه به بررسی ارزش تشخیصی این آزمایش در مقابل کرایتریای کالج روماتولوژی آمریکا که استاندارد تشخیصی آرتریت روماتویید است، پرداختیم. روش‌ها: مطالعه‌ی حاضر یک مطالعه از نوع توصیفی و ارزیابی ارزش تشخیصی بود. 98 بیمار که 49 نفر از آن‌ها مبتلا به آرتریت روماتویید و 49 نفر دیگر مبتلا به سایر بیماری‌های روماتولوژیک غیر آرتریت روماتویید و با تظاهرات مختلف روماتولوژیک بودند، مورد مطالعه قرار گرفتند. نمونه‌ی خون بیماران جهت بررسی از نظر Anti-CCP، فاکتور روماتویید (Rheumatoid factor یا RF)، سرعت رسوب گلبولی (Erythrocyte sedimentation rate یا ESR) به آزمایشگاه ارسال گردید و سپس فعالیت بیماری توسط DAS28 (Disease activity score) اندازه‌گیری شد. نتایج توسط نرم افزار SPSS نسخه‌ی 15 و آزمون 2χ آنالیز گردید. برای تعیین نقاط Trades offs از نمودار ROC (Receiver operating characteristic) استفاده شد. یافته‌ها: حساسیت و ویژگی Anti-CCP در تشخیص قطعی بیماری به ترتیب 71 و 80 درصد بود. همچنین ارزش اخباری مثبت این آزمایش 78 درصد، ارزش اخباری منفی74 درصد و نیز نسبت درست‌نمایی مثبت 55/3 و نسبت درست‌نمایی منفی 36/0 بود. در این مطالعه ارتباط بین Anti-CCP و RFاز نظر آماری معنی‌دار بود (001/0 > P). نتیجه‌گیری: آزمایش Anti-CCP دارای ارزش تشخیصی بالایی در بیماران آرتریت روماتویید می‌باشد.

PubMedID: 22090005 Articular symptoms are common in SSc and joint pain is a frequent presenting feature of this disease. Hand involvement is often the Wrst clinical manifestation of SSc and could be resulted from Wbrosis or synovitis or an overlap syndrome with rheumatoid arthritis (RA); though, the latter is a controversy in practice. To deWne the clues when identifying the nature of the hand arthropathy in SSc. In order to determine the hand arthropathy, serological tests, hand radiography, Wnger-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 Wndings in SSc patients were: Erosions 25%, joint space narrowing 17.9%, arthritis 10.7%, radiological demineralisation 42.9%, acro-osteolysis 25%, Xexion 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 Wndings. (Among them, only one patient had positive anti-CCP result). The remainder (9 patients) had no radiological or serological Wnding 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. © Springer-Verlag 2011.

Aim: Lung involvement substantially increases the morbidity and mortality rates in patients with rheumatoid arthritis (RA), thus, the early detection of lung involvement is essential for proper management. Several recent reports revealed that anti-CCP is an important parameter in the early diagnosis of RA and is closely related with the extraarticular manifestations of the disease. The aim of this study was to determine the relationship between serum anti-CCP antibodies and disease activity score-28 (DAS28), using the Stanford Health Assessment Questionnaire (HAQ) in patients with RA, whose pulmonary involvement was detected by computed tomography (CT). Methods: According to the high-resolution CT findings, the patients were divided into two groups - with pulmonary involvement (24 patients), and without a pulmonary disease (25 patients). Results: Statistically significant association was not found between pulmonary involvement and anti-CCP antibodies. There was no significant correlation between pulmonary involvement and disease activity evaluated by the HAQ. Conclusion: The disease activity determined by the DAS28 was significantly negatively correlated with pulmonary involvement (The Medical Bulletin of Haseki 2010; 48: 142-5)

INTRODUÇÃO/OBJETIVO: Caracterizar uma população de pacientes com artrite reumatoide (AR) inicial quanto aos aspectos laboratoriais, comparando-a com outras coortes similares. PACIENTES E MÉTODOS: Os dados apresentados fazem parte de um estudo prospectivo de coorte incidente, em que foram avaliados 65 pacientes com AR inicial, acompanhados por 36 meses a partir do diagnóstico, na Clínica de Artrite Reumatoide Inicial do Hospital Universitário de Brasília (HUB). Foram registrados os dados demográficos, clínicos e laboratoriais pertinentes à avaliação inicial da coorte, incluindo hematimetria, provas de atividade inflamatória e presença de autoanticorpos (fator reumatoide - FR, anticorpos antipeptídeos citrulinados cíclicos - anti-CCP e antivimentina citrulinada - anti-Sa). RESULTADOS: Houve predomínio de mulheres (86%), com média de idade de 45,6 anos. Doze pacientes (18,46%) tiveram o diagnóstico laboratorial de anemia (hemoglobina < 12 g/dL). Velocidade de hemossedimentação (VHS) e proteína C reativa (PCR) encontravam-se acima do valor de referência em 51 (78,46%) e 46 (70,76%) pacientes, respectivamente. Trinta e dois indivíduos (49,23%) foram positivos para pelo menos um dos isotipos de FR, sendo que 28 pacientes (43,07%) foram positivos para FR IgA, 19 (29,23%) para FR IgG e 32 (49,23%) para FR IgM, respectivamente; 34 pacientes (52,30% do total) foram positivos para pelo menos uma das técnicas utilizadas na averiguação de anti-CCP (CCP2, CCP3 ou CCP3.1), enquanto 9 (13,85%) o foram para anti-Sa. CONCLUSÕES: As características laboratoriais dos pacientes acompanhados nessa coorte brasileira se assemelham em vários aspectos a coortes norte-americanas, europeias e latino-americanas anteriormente publicadas.INTRODUCTION/OBJECTIVE: To characterize a population of patients with early rheumatoid arthritis (RA) according to laboratory aspects, comparing it with other similar cohorts. METHODS: Data presented are part of a prospective incident cohort study that evaluated 65 patients with early RA, followed for 36 months from the diagnosis at Early Rheumatoid Arthritis Clinic of Hospital Universitário de Brasília (HUB). We recorded demographics, clinical, and laboratory data relevant to the cohort initial assessment, including red blood cells, evidence of inflammatory activity, and presence of autoantibodies (rheumatoid factor (RF)), cyclic citrullinated peptide antibodies (anti-CCP), and antivimentin citrullinated (anti-Sa). RESULTS: There was a preponderance of female (86%) with mean age of 45.6 years. Twelve patients (18.46%) had laboratory diagnosis of anemia (hemoglobin < 12 g / dL). Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were above the reference value for 51 (78.46%) and 46 (70.76%) patients, respectively. Thirty-two patients (49.23%) were positive for at least one of the RF isotypes, and 28 patients (43.07%) were positive for IgA RF, 19 (29.23%) for IgG, and 32 ( 49.23%) for IgM RF, respectively; 34 patients (52.30%) were positive for at least one of the techniques used in investigation of anti-CCP (CCP2, or CCP3, or CCP3.1), while 9 (13,85%) were positive for anti-Sa. CONCLUSIONS: The laboratory characteristics of patients enrolled in this Brazilian cohort are similar in many respects to those of North-American, European, and Latin-American cohorts previously published.

The aim of the present work was to study the effect of tobacco smoking on disease progression in rheumatoid arthritis patients and its relation to anti-cyclical citrullinated peptide (anti-CCP) antibodies. The study included 54 patients; 20 non-smokers, 9 ex-smokers, 14 mild to moderate smokers and 11 heavy smokers. Fifteen normal volunteers were also studied as controls. Disease stage was clinically and radiologically determined, rheumatoid factor (RF) and anti-CCP antibodies were measured in serum. Higher percentage of severe disease (stage III) was seen in heavy smoker patients than mild to moderate smokers (54.6% versus 35.7%) and in moderate smokers than ex-smokers (35.7% versus 33.6%). Lowest percentage of severe disease was seen in non-smokers (15%). RF and anti-CCP were significantly higher in smoker than non-smoker and in heavy than mild to moderate smoker patients (p

WOS: 000276859300003, Objective: Differentiation of rheumatoid arthritis (RA) from other diseases with joint involvement such as hepatitis-C virus (HCV) infection represents a diagnostic problem. In addition to the rheumatoid factor (RF), more specific and sensitive auto-antibodies are under evaluation in recent years with conflicting results. In this study, we tested the diagnostic value of rheumatoid factor, anti-cyclic citrullinated peptide (anti-CCP) and anti-mutated citrullinated vimentin (anti-MCV) in distinguishing RA from hepatitis C patients. Materials and Methods: Sera of 34 RA patients and 30 hepatitis C patients were tested for RF, anti-CCP anti-MCV. Disease activity was determined by disease activity score (DAS-28) 28 in RA and by modified Knodell score in hepatitis C patients. Extra-articular involvement in RA and rheumatologic involvement in hepatitis C patients were documented. Results: In roc analysis, area under curve (AUC) was the highest in anti-CCP. Sensitivity and specificity was 82% and 53%, 79%, and 96% and 70%, and 73% for RF, anti-CCP and anti-MCV respectively. DAS-28 has a weak correlation with RF (r=0.406), anti-CCP (r=0.433), and anti-MCV (r=0.453). There was no difference between the patients in autoantibody levels regarding extra-articular involvement and DAS-28 in RA, and joint involvement in hepatitis C patients. Conclusion: Anti-MCV antibodies may be useful in distinguishing RA however it seems to have no additional value over anti-CCP or RF in hepatitis C patients. Anti-CCP antibodies are more reliable in diagnosis of RA due to their high specificity. (Turk J Rheumatol 2010; 25: 19-23)