Anti-citrullinated Protein/peptide Antibodies Research Articles

Neutrophilic Activity Biomarkers (Plasma Neutrophil Extracellular Traps and Calprotectin) in Established Patients with Rheumatoid Arthritis Receiving Biological or JAK Inhibitors: A Clinical and Ultrasonographic Study.

This study assesses the accuracy of neutrophil activation markers, including neutrophil extracellular traps (NETs) and calprotectin, as biomarkers of disease activity in patients with established rheumatoid arthritis (RA). We also analyse the relationship between NETs and various types of therapies as well as their association with autoimmunity. Observational cross-sectional study of patients with RA receiving treatment with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (JAK-inhibitors) for at least 3months. Plasma calprotectin levels were measured using an enzyme-linked immunosorbent assay test kit and NETs by measuring their remnants in plasma (neutrophil elastase-DNA and histone-DNA complexes). We also assessed clinical disease activity, joint ultrasound findings and autoantibody status [reumatoid factor (RF), anti-citrullinated peptide/protein antibodies (ACPAs) and anti-carbamylated protein (anti-CarP)]. Associations between neutrophilic biomarkers and clinical or ultrasound scores were sought using correlation analysis. The discriminatory capacity of both neutrophilic biomarkers to detect ultrasound synovitis was analysed through receiver-operating characteristic (ROC) curves. One hundred fourteen patients were included. Two control groups were included to compare NET levels. The active control group consisted of 15 patients. The second control group consisted of 30 healthy subjects. Plasma NET levels did not correlate with clinical disease status, regardless of the clinic index analysed or the biological therapy administered. No significant correlation was observed between NET remnants and ultrasound synovitis. There was no correlation between plasma NET and autoantibodies. In contrast, plasma calprotectin positively correlated with clinical parameters (swollen joint count [SJC] rho = 0.49; P < 0.001, Clinical Disease Activity Index [CDAI] rho = 0.30; P < 0.001) and ultrasound parameters (rho > 0.50; P < 0.001). Notably, this correlation was stronger than that observed with acute phase reactants. While NET formation induced by neutrophils may play a role in RA pathogenesis, our study raises questions about the utility of NET remnants in peripheral circulation as a biomarker for inflammatory activity. In contrast, this study strongly supports the usefulness of calprotectin as a biomarker of inflammatory activity in patients with RA.

Drug Retention Rates and the Safety of Janus Kinase Inhibitors in Elderly Patients with Rheumatoid Arthritis.

We examined the real-world drug retention rate and safety data of Janus kinase inhibitors (JAKis) in elderly patients with rheumatoid arthritis (RA). This study enrolled 133 RA patients (≥65 years) with sufficient clinical data who were initiated with JAKis during the study period. These patients were divided into two groups: the very elderly group (≥ 75 years) and the elderly group (65 ≤ years < 75). The drug retention rates of JAKis were compared using Kaplan-Meier curves. The discontinuation rates of JAKis were as follows: lack of effectiveness 27 (20.3%), adverse events (AEs) 29 (21.8%), and remission 2 (1.5%). There was no significant difference in the overall drug retention rate between the very elderly group (≥75 years) and the elderly group. Furthermore, the overall drug retention rates of JAKis were not affected by gender, methotrexate use, and anti-citrullinated protein/peptide antibody (ACPA) status. The discontinuation rates of JAKis due to AEs were comparable both in the very elderly group (≥75 years) and the elderly group (65 ≤ years < 75). Whereas chronic lung disease and hypoalbuminemia were independently associated with discontinuation rates due to AEs, the overall drug retention rates were significantly lower in patients treated with the approved dose of JAKis than in those treated with a reduced or tapered dose. Our results suggest that the overall drug retention rate of JAKis in very elderly patients (≥75 years) was comparable with that in elderly patients (65 ≤ years < 75). The discontinuation rates of JAKis due to AEs were also comparable both in very elderly group patients and elderly patients.

Multicentre study to improve clinical interpretation of rheumatoid factor and anti-citrullinated protein/peptide antibodies test results

BackgroundRheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA) are important biomarkers for diagnosis of rheumatoid arthritis (RA). However, there is poor harmonisation of RF and ACPA assays. The aim of...

Medication Dosing Error Leading to Potentially Lethal Methotrexate Toxicity

Pancytopenia is a rare consequence of rheumatoid arthritis treatment with low-dose methotrexate. Several literature reviews discovered earlier examples of severe pancytopenia caused by low- dose or dosage error of methotrexate. We discuss the case of a 67-year-old ACPA (Anti- citrullinated protein/peptide antibody) positive rheumatoid arthritis patient who had severe pancytopenia and oral mucositis as a result of methotrexate toxicity. To reduce medication dosing errors, we highlight its uncommon dose schedule.

Medication Dosing Error Leading to Potentially Lethal Methotrexate Toxicity

Pancytopenia is a rare consequence of rheumatoid arthritis treatment with low-dose methotrexate. Several literature reviews discovered earlier examples of severe pancytopenia caused by low- dose or dosage error of methotrexate. We discuss the case of a 67-year-old ACPA (Anti- citrullinated protein/peptide antibody) positive rheumatoid arthritis patient who had severe pancytopenia and oral mucositis as a result of methotrexate toxicity. To reduce medication dosing errors, we highlight its uncommon dose schedule.

Impact of Posttranslational Modification in Pathogenesis of Rheumatoid Arthritis: Focusing on Citrullination, Carbamylation, and Acetylation.

Rheumatoid arthritis (RA) is caused by prolonged periodic interactions between genetic, environmental, and immunologic factors. Posttranslational modifications (PTMs) such as citrullination, carbamylation, and acetylation are correlated with the pathogenesis of RA. PTM and cell death mechanisms such as apoptosis, autophagy, NETosis, leukotoxic hypercitrullination (LTH), and necrosis are related to each other and induce autoantigenicity. Certain microbial infections, such as those caused by Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Prevotella copri, can induce autoantigens in RA. Anti-modified protein antibodies (AMPA) containing anti-citrullinated protein/peptide antibodies (ACPAs), anti-carbamylated protein (anti-CarP) antibodies, and anti-acetylated protein antibodies (AAPAs) play a role in pathogenesis as well as in prediction, diagnosis, and prognosis. Interestingly, smoking is correlated with both PTMs and AMPAs in the development of RA. However, there is lack of evidence that smoking induces the generation of AMPAs.

In Rheumatoid Arthritis Patients, HLA-DRB1*04:01 and Rheumatoid Nodules Are Associated With ACPA to a Particular Fibrin Epitope.

ObjectivesRheumatoid arthritis (RA) is associated with HLA-DRB1 genes encoding the shared epitope (SE), a 5-amino acid motive. RA is usually preceded by the emergence of anti-citrullinated protein/peptide antibodies (ACPAs). Citrulline is a neutral amino acid resulting from post-translational modification of arginine involved in peptidic bounds (arginyl residue) by PeptidylArginine Deiminases (PADs). ACPAs recognize epitopes from citrullinated human fibrin(ogen) (hFib) and can be specifically detected by the AhFibA assay. Five citrullinated peptides derived from hFib together represent almost all of the epitopes recognized by patients with ACPA-positive RA, namely: α36–50cit, α171–185cit, α501–515cit, α621–635cit, and β60–74cit. The use of antibody fine specificities as markers of clinical phenotypes has become a major challenge. Our objective was to study whether RA clinical characteristics and HLA-DRB1 genetic background were associated with a specific reactivity against the epitopes borne by the five peptides.Methods184 ACPA-positive RA patients fulfilling the 2010 ACR/EULAR criteria were studied. Patient characteristics including HLA-DRB1 genotype, were collected from their medical files. Anti-CCP2 antibodies, AhFibA, and antibodies against the five citrullinated hFib (hFib-cit) peptides were analyzed by ELISA.ResultsAnti-α505-515cit antibodies were associated with HLA-DRB1*04:01 (OR = 5.52 [2.00 – 13.64]; p = 0.0003). High level anti-α505-515cit antibodies were associated with rheumatoid nodules (OR = 2.71 [1.00 – 7.16], p= 0.044).ConclusionImmune complexes containing anti-α501-515cit antibodies and rheumatoid factors might be involved in the development of rheumatoid nodules on the HLA-DRB1*04:01 background. Apheresis of these epitope-specific antibodies might be a new therapeutic opportunity for patients with rheumatoid nodules.

Autoantibodies in Rheumatoid Arthritis - Laboratory and Clinical Perspectives.

Measurement of two groups of autoantibodies, rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA) have gained increasing significance in the diagnosis and classification of rheumatoid arthritis (RA) over the last 65 years. Despite this rising importance of autoimmune serology in RA, there is a palpable lack of harmonization between different commercial RF and ACPA tests. While a minimal diagnostic specificity has been defined for RF tests, which almost always are related to an international reference preparation, neither of this applies to ACPA. Especially assays with low diagnostic specificity are associated with very low positive predictive values or post-test probabilities in real world settings. In this review we focus on issues of practical bearing for the clinical physician diagnosing patients who potentially have RA, or treating patients diagnosed with RA. We advocate that all clinically used assays for RF and ACPA should be aligned to a common diagnostic specificity of 98-99% compared to healthy controls. This high and rather narrow interval corresponds to the diagnostic specificity seen for many commercial ACPA tests, and represents a specificity that is higher than what is customary for most RF assays. Data on antibody occurrence harmonized in this way should be accompanied by test result-specific likelihood ratios for the target diagnosis RA on an ordinal or interval scale, which will provide the clinical physician with more granular and richer information than merely relating numerical values to a single cut-off point. As many physicians today are used to evaluate autoantibodies as positive or negative on a nominal scale, the introduction of test result-specific likelihood ratios will require a change in clinical mindset. We also discuss the use of autoantibodies to prognosticate future arthritis development in at-risk patients as well as predict severe disease course and outcome of pharmacological treatment.

Recombinant Factor C Validation-Simpler Than You Think!

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Subjects at-risk for future development of rheumatoid arthritis demonstrate a PAD4-and TLR-dependent enhanced histone H3 citrullination and proinflammatory cytokine production in CD14hi monocytes.

The presence of anti-citrullinated protein/peptide antibodies (ACPA) and epitope spreading across the target autoantigens is a unique feature of rheumatoid arthritis (RA). ACPA are present in the peripheral blood for several years prior to the onset of arthritis and clinical classification of RA. ACPA recognize multiple citrullinated proteins, including histone H3 (H3). Intracellular citrullination of H3 in neutrophils and T cells is known to regulate immune cell function by promoting neutrophil extracellular trap formation and citrullinated autoantigen release as well as regulating the Th2/Th17T cell phenotypic balance. However, the roles of H3 citrullination in other immune cells are not fully elucidated. We aimed to explore H3 citrullination and cytokine/metabolomic signatures in peripheral blood immune cells from subjects prior to and after the onset of RA, at baseline and in response to ex vivo toll-like receptor (TLR) stimulation. Here, we analyzed 13 ACPA (+) subjects without arthritis but at-risk for future development of RA, 14 early RA patients, and 13 healthy controls. We found significantly elevated H3 citrullination in CD14hi monocytes, as well as CD1c+ dendritic cells and CD66+ granulocytes. Unsupervised analysis identified two distinct subsets in CD14hi monocytes characterized by H3 modification and unique cytokine/metabolomic signatures. CD14hi monocytes with elevated TLR-stimulated H3 citrullination were significantly increased in ACPA (+) at-risk subjects. These cells were skewed to produce TNFα, MIP1β, IFNα, and partially IL-12. Additionally, they demonstrate peptidyl arginine deiminase 4 (PAD4) mediated upregulation of the glycolytic enzyme PFKFB3. These CD14hi monocytes with elevated H3 citrullination morphologically formed monocyte extracellular traps (METs). Taken together, dysregulated PAD4-driven cytokine production as well as MET formation in CD14hi monocytes in ACPA (+) at-risk subjects likely plays an important role in the development of RA via promoting and perpetuating inflammation and generation of citrullinated autoantigens.

Fluctuation in anti-cyclic citrullinated protein antibody level predicts relapse from remission in rheumatoid arthritis: KURAMA cohort

BackgroundThe positivity of anti-citrullinated protein/peptide antibodies (ACPAs) is a clinically useful diagnostic and prognostic marker in rheumatoid arthritis (RA). However, the significance of ACPA titer and its fluctuation remain unclear. This study aimed to assess the role of ACPA titer and its fluctuation on disease activity and the prognosis of RA.MethodsData obtained from the Kyoto University Rheumatoid Arthritis Management Alliance (KURAMA) cohort was analyzed. Patients whose ACPA was measured at least twice between 2011 and 2019 and whose ACPA was positive at least once were included in this study. The association between the clinical variable and ACPA titer or its change was investigated.ResultsACPA titer was measured in a total of 3286 patients, 1806 of whom were ACPA-positive at least once. Among them, the ACPA titer level was measured more than once in 1355 patients. Very weak correlation was observed between the ACPA titer level and disease activity. Additionally, there was no trend in the fluctuation of ACPA titer level in each patient; ACPA titer level fluctuated in some patients, but not in others. Patients with high variable levels of ACPA titer were more likely to relapse from remission. In the analysis of two consecutive ACPA measurements, the titer changes predicted the relapse from remission within a year of the second measurement.ConclusionsThe ACPA titer level fluctuated in some patients. Very weak correlation was observed between the ACPA titer level and disease activity. Fluctuation in ACPA titer level predicted relapse from remission in patients with RA.

Meta-analysis: diagnostic accuracy of the citrullinated peptides derived from fibrinogen and vimentin in rheumatoid arthritis.

Anticitrullinated protein/peptide antibodies (ACPAs) have shown valuable effects in the diagnosis of rheumatoid arthritis (RA). Both fibrinogen and vimentin are significant antigens of ACPAs. This study evaluated the diagnostic performance of fibrinogen and vimentin peptides in RA. We searched the PubMed, Embase, and Cochrane Library databases for studies published in English until January 2019 that evaluated the utility of the peptides of both vimentin and fibrinogen. The bivariate mixed-effects model and summary receiver operating characteristic (SROC) curve were used to estimate sensitivity and specificity across studies. Seven peptides from 19 studies were included. The pooled sensitivities of Fibα36-50, Fibα563-583, Fibα580-600, Fibα621-635, Fibβ36-52, Fibβ60-74, and Vim60-75 were 35%, 41%, 18%, 26%, 0.53%, 57%, and 44%, respectively. The pooled specificities of Fibα36-50, Fibα563-583, Fibα580-600, Fibα621-635, Fibβ36-52, Fibβ60-74, and Vim60-75 were 97%, 98%, 98%, 98%, 97%, 98%, and 98%, respectively. The SROC areas under the curve (AUCs) of Fibα36-50, Fibα563-583, Fibα580-600, Fibα621-635, Fibβ36-52, Fibβ60-74, and Vim60-75 were 0.92, 0.85, 0.64, 0.82, 0.91, 0.96, and 0.86, respectively. Both fibrinogen and vimentin peptides have a high specificity but a relatively low sensitivity in diagnosing RA. The diagnostic accuracies of Fibβ60-74 and Fibβ36-52 were better than those of Vim60-75, Fibα36-50, and Fibα563-583, and all of them were better than that of Fibα621-635 and Fibα580-600.Key Points• Our study summarized the diagnostic accuracy of peptides derived from fibrinogen and vimentin and evaluated the diagnostic value of different peptides for RA patients.• Both fibrinogen and vimentin peptides have a high specificity but a relatively low sensitivity in diagnosing RA.

Autoantibodies as Diagnostic Markers and Mediator of Joint Inflammation in Arthritis.

Rheumatoid arthritis is a systemic, polygenic, and multifactorial syndrome characterized by erosive polyarthritis, damage to joint architecture, and presence of autoantibodies against several self-structures in the serum and synovial fluid. These autoantibodies (anticitrullinated protein/peptide antibodies (ACPAs), rheumatoid factors (RF), anticollagen type II antibodies, antiglucose-6 phosphate isomerase antibodies, anticarbamylated protein antibodies, and antiacetylated protein antibodies) have different characteristics, diagnostic/prognostic value, and pathological significance in RA patients. Some of these antibodies are present in the patients' serum several years before the onset of clinical disease. Various genetic and environmental factors are associated with autoantibody production against different autoantigenic targets. Both the activating and inhibitory FcγRs and the activation of different complement cascades contribute to the downstream effector functions in the antibody-mediated disease pathology. Interplay between several molecules (cytokines, chemokines, proteases, and inflammatory mediators) culminates in causing damage to the articular cartilage and bones. In addition, autoantibodies are proven to be useful disease markers for RA, and different diagnostic tools are being developed for early diagnosis of the clinical disease. Recently, a direct link was proposed between the presence of autoantibodies and bone erosion as well as in the induction of pain. In this review, the diagnostic value of autoantibodies, their synthesis and function as a mediator of joint inflammation, and the significance of IgG-Fc glycosylation are discussed.

Anticitrullinated protein antibodies facilitate migration of synovial tissue-derived fibroblasts

ObjectivesRheumatoid arthritis (RA)-specific anti-citrullinated protein/peptide antibodies (ACPAs) might contribute to bone loss and arthralgia before the onset of joint inflammation. We aimed to dissect additional mechanisms by which ACPAs might...

Extracellular traps and PAD4 released by macrophages induce citrullination and auto-antibody production in autoimmune arthritis

The mechanisms underlying the transition of rheumatoid arthritis (RA) systemic autoimmunity to the joints remain largely unknown. Here, we demonstrate that macrophages in the secondary lymphoid organs (SLOs) and synovial ectopic lymphoid-like structures (ELSs) express peptidylarginine deiminase 4 (PAD4) in murine collagen induced arthritis (CIA) and synovial biopsies from RA patients. Moreover, peptidyl citrulline colocalized with macrophages in SLOs and ELSs, and depletion of macrophages in CIA decreased lymphoid tissue citrullination and serum anti-citrullinated protein/peptide antibody (ACPA) levels. Furthermore, PAD was released from activated murine and RA synovial tissue and fluid (SF) macrophages which functionally deiminated extracellular proteins/peptides in vitro. Additionally, activated murine and SF macrophages displayed macrophage extracellular trap formation (METosis) and release of intracellular citrullinated histones. Moreover, presentation of citrullinated proteins induced ACPA production in vitro. Thus, lymphoid tissue macrophages contribute to self-antigen citrullination and ACPA production, indicating that their selective targeting would potentially ameliorate citrullination-dependent autoimmune disorders.

Development of a multiplex assay based on chimeric citrullinated peptides as proof of concept for diagnosis of rheumatoid arthritis.

Anti-citrullinated peptide/protein antibodies (ACPAs) are the most specific serological biomarkers for rheumatoid arthritis (RA). They have both diagnostic and prognostic value, and are related to more aggressive joint disease in RA. However, a single biomarker cannot differentiate RA subtypes. So, simultaneous analysis of target citrullinated peptides, using a multiplex array based on chimeric peptides composed of several domains of human proteins, could be useful. In this work, eight chimeric peptides and the corresponding native arginine-containing control peptides were obtained by solid-phase peptide synthesis. The study included RA and psoriatic arthritis (PsA) patients attending the Rheumatology Unit of the Hospital Clinic in Barcelona, as well as healthy blood donors (BD) at the same hospital. Our main aim was to explore the diagnostic value of the novel multiplex array compared to a commercial ELISA-based ACPA assay in a serum-saving way. Using the combination of the eight chimeric peptide antigens in the multiplex array, 61.4% of the RA cohort were positive for 3 or more peptides; while, the healthy BD and PsA cohorts did not show any reactivity with the tested peptides. These results indicate that we have developed a highly specific multiplex assay based of chimeric citrullinated peptides derived from filaggrin, fibrin, vimentin and human enolase proteins for the detection of ACPAs in a serum-saving way.

Assessing prognosis and prediction of treatment response in early rheumatoid arthritis: systematic reviews.

Rheumatoid arthritis (RA) is a chronic, debilitating disease associated with reduced quality of life and substantial costs. It is unclear which tests and assessment tools allow the best assessment of prognosis in people with early RA and whether or not variables predict the response of patients to different drug treatments. To systematically review evidence on the use of selected tests and assessment tools in patients with early RA (1) in the evaluation of a prognosis (review 1) and (2) as predictive markers of treatment response (review 2). Electronic databases (e.g. MEDLINE, EMBASE, The Cochrane Library, Web of Science Conference Proceedings; searched to September 2016), registers, key websites, hand-searching of reference lists of included studies and key systematic reviews and contact with experts. Review 1 - primary studies on the development, external validation and impact of clinical prediction models for selected outcomes in adult early RA patients. Review 2 - primary studies on the interaction between selected baseline covariates and treatment (conventional and biological disease-modifying antirheumatic drugs) on salient outcomes in adult early RA patients. Review 1 - 22 model development studies and one combined model development/external validation study reporting 39 clinical prediction models were included. Five external validation studies evaluating eight clinical prediction models for radiographic joint damage were also included. c-statistics from internal validation ranged from 0.63 to 0.87 for radiographic progression (different definitions, six studies) and 0.78 to 0.82 for the Health Assessment Questionnaire (HAQ). Predictive performance in external validations varied considerably. Three models [(1) Active controlled Study of Patients receiving Infliximab for the treatment of Rheumatoid arthritis of Early onset (ASPIRE) C-reactive protein (ASPIRE CRP), (2) ASPIRE erythrocyte sedimentation rate (ASPIRE ESR) and (3) Behandelings Strategie (BeSt)] were externally validated using the same outcome definition in more than one population. Results of the random-effects meta-analysis suggested substantial uncertainty in the expected predictive performance of models in a new sample of patients. Review 2 - 12 studies were identified. Covariates examined included anti-citrullinated protein/peptide anti-body (ACPA) status, smoking status, erosions, rheumatoid factor status, C-reactive protein level, erythrocyte sedimentation rate, swollen joint count (SJC), body mass index and vascularity of synovium on power Doppler ultrasound (PDUS). Outcomes examined included erosions/radiographic progression, disease activity, physical function and Disease Activity Score-28 remission. There was statistical evidence to suggest that ACPA status, SJC and PDUS status at baseline may be treatment effect modifiers, but not necessarily that they are prognostic of response for all treatments. Most of the results were subject to considerable uncertainty and were not statistically significant. The meta-analysis in review 1 was limited by the availability of only a small number of external validation studies. Studies rarely investigated the interaction between predictors and treatment. Collaborative research (including the use of individual participant data) is needed to further develop and externally validate the clinical prediction models. The clinical prediction models should be validated with respect to individual treatments. Future assessments of treatment by covariate interactions should follow good statistical practice. Review 1 - uncertainty remains over the optimal prediction model(s) for use in clinical practice. Review 2 - in general, there was insufficient evidence that the effect of treatment depended on baseline characteristics. This study is registered as PROSPERO CRD42016042402. The National Institute for Health Research Health Technology Assessment programme.

Changes in anti-citrullinated protein antibody isotype levels in relation to disease activity and response to treatment in early rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease where serum analysis of anti-citrullinated peptide/protein antibodies (ACPA) is an important diagnostic/prognostic tool. Levels and changes of ACPA in RA patients have been studied previously in relation to disease course and therapy response, but less is known regarding ACPA isotype changes in early RA. Hence, recent-onset RA patients (n=231) were subjected to a 3-year clinical and radiological follow-up. Serum samples were serially collected and ACPA isotypes were analysed using the second-generation cyclic citrullinated peptide (CCP) as capture antigen. Changes in ACPA isotype levels and status were related to disease course and pharmacotherapy. At inclusion, 74% of the patients tested positive for ACPA IgG; 55% for immunoglobulin (Ig)A, 37% for secretory IgA (SIgA) and 35% for IgM. The proportion of positive patients decreased significantly at follow-up regarding ACPA SIgA, IgM and IgA. During the initial 3months, reduction of the 28-joint disease activity score (DAS28) correlated with reduced levels of ACPA IgG (Rho=0·242, P=0·003), IgA (Rho=0·260, P=0·008), IgM (Rho=0·457, P<0·001) and SIgA (Rho=0·402, P<0·001). Levels of ACPA SIgA (P=0·008) and IgM (P=0·021) decreased significantly among patients with good response to treatment, which was not seen regarding ACPA IgA or IgG. Changes in ACPA isotype levels were not associated with radiographic damage. In conclusion, ACPA SIgA and IgM declined rapidly upon anti-rheumatic therapy and correlated with decreased disease activity in recent-onset RA. This may indicate that down-regulation of mucosal immunity to citrullinated proteins/peptides and recruitment of new B cells are key features of therapy responses in early RA.

Periodontal microbiota in a cohort of Egyptian patients with rheumatoid arthritis and their relation to serum and gingival anticitrullinated peptide protein antibodies and different disease parameters

ObjectiveThe possibility of infectious trigger at the gingival site in rheumatoid arthritis (RA) was reported in previous studies. The aim of our study is to determine the organisms causing periodontitis (PD) in a cohort of Egyptian patients with RA and their relation to serum and gingival anticitrullinated peptide protein antibodies (ACPA) level and other disease parameters.Patients and methodsA prospective cohort study was conducted on 100 consecutive Egyptian patients with RA. Disease activity was assessed by applying disease activity score-28, and functional status was measured using health assessment questionnaire. Dental examination, serum rheumatoid factor, ACPA in serum and gingival crevicular fluid (GCF), and radiograph of the hands were done for all patients. GCF culture was performed for all cases with PD for Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans (Aa), and Prevotella intermedia (Pi).ResultsOf the 100 patients, 66 patients had PD; of them, GCF culture was performed, and Pg, Aa, and Pi were found in 60.6, 15.2, and 30.3% of patients with RA with PD, respectively. Gingival ACPA showed significant higher level with Pg than Pi cases (P=0.047). No statistically significant difference was detected on comparing Pg with Aa or Aa with Pi. Aa-positive cases were associated with significantly higher level of C-reactive protein than Pi-positive cases (P=0.029), whereas no statistical significant difference was detected between Pg- and Aa-positive or Pi-positive cases.ConclusionOur findings support the relationship between PD and infectious trigger at the gingival site and RA. Pg is the most prevalent periodontal microbiota in our cohort of patients with RA with PD that is associated with significant higher level of gingival ACPA. None of the detected organisms correlated with the degree of RA activity or other disease parameters, apart from significantly higher C-reactive protein level with Aa.

Interstitial lung disease associated with anti-citrullinated peptide/protein antibody-positive anti-synthetase syndrome

Little has been reported on the characteristics of interstitial lung disease (ILD) associated with anti-citrullinated peptide/protein antibody (ACPA)-positive anti-synthetase syndrome (ASS). We sought to investigate the clinical, radiologic, and pathologic features of patients with ILD associated with ACPA-positive ASS. Medical records of seven ILD patients with positive results of both ACPA and anti-aminoacyl-tRNA synthetase antibody were retrospectively reviewed. Five patients had clinical symptoms associated with ASS other than ILD. On high-resolution computed tomography (HRCT) analysis, a nonspecific interstitial pneumonia (NSIP) pattern was shown in 3 patients and NSIP with organizing pneumonia (OP) overlap in 2 patients. Coronal slices of these 5 patients showed lower lung disease predominance with traction caudally on major fissures due to lower lobe volume loss. These were features that could commonly be observed in ASS-associated ILD. Pathological findings available for 3 patients showed NSIP. The characteristics of ILD associated with ACPA-positive ASS appear to be similar to those of ILD associated with ASS, but not to rheumatoid arthritis (RA) or ACPA, especially in terms of the radiological findings.