Anti-cyclic Citrullinated Antibodies Research Articles

Serum alarmins and the risk of incident interstitial lung disease in rheumatoid arthritis.

To quantify associations of serum alarmins with risk of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Using serum collected at enrolment, three alarmins (IL-33, thymic stromal lymphopoietin [TSLP] and IL-25) were measured in a multicentre prospective RA cohort. ILD was classified using systematic medical record review. Cross-sectional associations of log-transformed (IL-33, TSLP) or quartile (IL-25) values with RA-ILD at enrolment (prevalent RA-ILD) were examined using logistic regression, while associations with incident RA-ILD developing after enrolment were examined using Cox proportional hazards. Covariates in multivariate models included age, sex, race, smoking status, RA disease activity score and anti-cyclic citrullinated antibody positivity. Of 2835 study participants, 115 participants (4.1%) had prevalent RA-ILD at baseline and an additional 146 (5.1%) developed incident ILD. There were no associations between serum alarmin concentrations and prevalent ILD in unadjusted or adjusted logistic regression models. In contrast, there was a significant inverse association between IL-33 concentration and the risk of developing incident RA-ILD in unadjusted (hazard ratio [HR] 0.73 per log-fold increase; 95% CI: 0.57, 0.95; P = 0.018) and adjusted (HR 0.77; 95% CI: 0.59, 1.00; P = 0.047) models. No significant associations of TSLP or IL-25 with incident ILD were observed. In this study, we observed a significant inverse association between serum IL-33 concentration and the risk of developing incident RA-ILD, but no associations with prevalent ILD. Additional investigation is required to better understand the mechanisms driving this relationship and how serum alarmin IL-33 assessment might contribute to clinical risk stratification in patients with RA.

THE PREVALENCE OF EYE INVOLVEMENTS IN RHEUMATOID ARTHRITIS AND THEIR CORRELATION WITH ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODY IN SULAIMANI GOVERNORATE/IRAQ

BackgroundRheumatoid arthritis is a common autoinflammatory disease that affects the joints and causes several extra-articular problems, including ocular involvement, which typically manifests in the anterior ocular region. The anti-CCP has a sensitivity comparable to the rheumatoid factor and higher specificity for identifying the disease.
 ObjectivesTo estimate the prevalence of eye involvements in Rheumatoid arthritis and their correlation to the anti-cyclic citrullinated peptide antibody.
 Patients and MethodsA cross-sectional study of 121 patients who satisfied the 2010 ACR/EULAR RA Classification Criteria (6/10 or more points) were between 18 and 60. After establishing a patient’s medical history and physical examination, blood samples were collected to test for anti-CCP antibodies, and an eye exam was conducted.
 ResultsThere were significantly more females than males;104 (86%) were female, and 17 (14%) were males. The median age was 47(42−53.5) years. The median disease duration was 4(2−10) years. The mean disease activity was 3.86 ±1, and the median anti-cyclic citrullinated antibody titers were 29.18(16.75−133.35) U/ml. The overall eye complications typical of Rheumatoid arthritis were observed in 37 (30.6%) and 84 (69.4%) without eye involvement. Dry eyes were the most frequent eye complaint (29.8%). One instance with episcleritis (0.8%). One with filamentary keratitis (0.8%). Anterior uveitis was detected in two cases (1.7%). Eye involvement correlated with anti-cyclic citrullinated peptide antibody (P- value 0.004).
 ConclusionEye manifestations of rheumatoid arthritis were a prominent part of extra-articular manifestation. The dry eye was the most apparent manifestation, and they correlated to the anti-CCP antibody.

Anti-Saccharomyces cerevisiae Antibodies in Rheumatoid Arthritis.

This study was conducted to evaluate the frequency of anti-Saccharomyces cerevisiae antibodies (ASCA) in patients with rheumatoid arthritis (RA). Eighty-three RA patients with positive anti-cyclic citrullinated antibodies (anti-CCP) and 160 healthy blood donors were included in this study. ASCA IgG and IgA were assessed with enzyme-linked immunosorbent assay. The frequency of ASCA was significantly higher in RA patients than in healthy subjects (22.9% vs 3.7%, P < 10-3). Both ASCA IgG and ASCA IgA were significantly more frequent in RA patients than in the control group (20.5% vs 3.1%, P < 10-3and 9.6% vs 0.6%, P = .002, respectively). ASCA IgG and ASCA IgA levels were significantly higher in RA patients than in healthy subjects (7.8 ± 8.4 U/mL vs 2.3 ± 2.8 U/mL, P < 10-6 and 6.2 ± 10.9 U/mL vs 3.4 ± 1.7 U/mL, P = .002, respectively). A high frequency of ASCA IgG and ASCA IgA has been found in RA patients.

Impact of Perceived Stress During the SARS-CoV-2 Pandemic on Rheumatoid Arthritis Patients' Disease Activity: An Online Survey.

Introduction/ObjectivesPsychological stress worsens rheumatoid arthritis (RA) disease activity, and the COVID-19 pandemic has increased stress/anxiety in rheumatic patients. The purpose of this study was to determine if stress during the COVID-19 pandemic specifically impacts RA disease activity as reported by the patient.MethodThis was a cross-sectional COVID-19 RA survey study. University of California, Los Angeles rheumatology clinic patients were emailed a link to a survey in July and November 2020. The 30-question survey pertained to COVID-19–related stress, RA disease activity, and demographics. For the survey responders, anti–cyclic citrullinated antibody, rheumatoid factor, and age were extracted from the electronic health record. Analyses were performed to examine the association between the 4-item Perceived Stress Scale (PSS-4) and other COVID-19–related stress measures with the Routine Assessment of Patient Index Data 3 (RAPID3).ResultsA total of 1138/5037 subjects completed the emailed survey (22.6% response rate). When examining responses across RAPID3 categories (near remission, low, moderate, and high disease severity), there were significant increases in PSS-4 and other stress variables. Multiple linear regression models showed that PSS-4, financial stress, age, seropositivity, disease duration, and Black race were independently associated with worsened RAPID3 scores, when controlling for other confounding factors.ConclusionsThis study suggests that stress overall negatively impacts RAPID3, and Black RA patients had a higher RAPID3 scores during the COVID-19 pandemic. Despite colossal efforts to combat the pandemic, RA patients currently suffer from stress/anxiety, and methods to mitigate these psychological effects are needed.

Constrictive (Obliterative) Bronchiolitis as Presenting Manifestation of Connective Tissue Diseases.

Constrictive (obliterative) bronchiolitis (CB) is an uncommon form of obstructive lung disease that can occur in patients with identifiable causes including connective tissue diseases (CTDs) as a form of lung involvement. We explored whether CB can be the presenting manifestation of CTD. We identified 44 patients with cryptogenic CB and examined the presenting clinical, laboratory, and radiologic features, as well as their clinical course. The mean age at presentation was 60.5 (SD, 13.8) years and included 38 women (86%); 32 (73%) were never smokers. All patients presented for evaluation of dyspnea, commonly associated with cough. An obstructive pattern on pulmonary function testing was demonstrated in 86% of patients. On chest high-resolution computed tomography, nearly all patients manifested a mosaic attenuation pattern with air trapping on expiratory views, characteristic of CB. Bronchoscopic lung biopsy (n = 10) was usually nondiagnostic (90%), whereas all 5 surgical lung biopsies yielded evidence of CB. Serologic testing for CTD was positive in 19 patients (43%) and most commonly included antinuclear antibody, rheumatoid factor, and anti-cyclic citrullinated antibodies. Seven of these patients with positive serologic results were eventually diagnosed to have CTD. Connective tissue diseases included rheumatoid arthritis in 4 patients, Sjögren syndrome in 2, and undifferentiated CTD in 1 patient. Nearly one-half of patients with cryptogenic CB manifest positive CTD serology, and some of these patients have CTD not previously diagnosed. These results suggest that CB can be the presenting manifestation of a CTD.

Intake frequency of vegetables or seafoods negatively correlates with disease activity of rheumatoid arthritis.

ObjectiveTo clarify the relationship between dietary habit and disease activity of rheumatoid arthritis (RA).MethodsThis study enrolled RA patients who met the ACR/EULAR 2010 classification criteria from Kyoto University Rheumatoid Arthritis Management Alliance (KURAMA) cohort in 2015. 22-item food frequency questionnaire (FFQ) was taken for the measurement of dietary habit in a single-institution cohort of RA (Kyoto University Rheumatoid Arthritis Management Alliance: KURAMA) in 2015. The disease activities of RA using the Disease Activity Score calculated based on the erythrocyte sedimentation rate (DAS28-ESR), Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire (HAQ), and serum matrix metalloproteinase-3 (MMP-3) level, the use of disease-modifying anti-rheumatic drugs (DMARDs), disease duration, rheumatoid factor, anti-cyclic citrullinated antibody, and body mass index were also examined. All of them were combined and statistically analyzed.Results441 RA patients (81% women; mean age 65 years; mean disease duration 15 years) were enrolled from the KURAMA cohort. Average Disease Activity Score-28 using the erythrocyte sedimentation rate (DAS28-ESR) was 2.7. Univariate analysis showed that intake frequency of vegetables had a statistically significant negative correlation with disease activity markers, such as DAS28-ESR (ρ = −0.11, p<0.01), Simplified Disease Activity Index (SDAI) (ρ = −0.16, p<0.001), matrix metalloproteinase-3 (MMP-3) (ρ = −0.21, p<0.0001), and Health Assessment Questionnaire (HAQ) (ρ = −0.13, p<0.01). Factor analysis with varimax rotation was done to simplify the relevance of disease activity to various food items. 22 foods were categorized into five dietary patterns: “seafoods”, “vegetables/fruits”, “meats/fried foods”, “snacks”, and “processed foods”. The multivariate analysis adjusted for clinically significant confounders showed that “seafoods” had statistically significant negative correlations with DAS28-ESR (β = −0.15, p<0.01), SDAI (β = −0.18, p<0.001), MMP-3 (β = −0.15, p<0.01), and HAQ (β = −0.24, p<0.0001). “Vegetables/fruits” had statistically significant negative correlations with SDAI (β = −0.11 p<0.05), MMP-3 (β = −0.12, p<0.01), and HAQ (β = −0.11, p<0.05)ConclusionsThese results suggest that high intake frequency of vegetables/fruits and/or seafoods might correlate with low disease activity.

IgA is the predominant isotype of anti-β2 glycoprotein I antibodies in rheumatoid arthritis.

BackgroundThe aim of this study was to determine the frequency of anti‐cardiolipin antibodies (aCL) and anti‐β2 glycoprotein I antibodies (aβ2GPI) among Tunisian patients with rheumatoid arthritis (RA).MethodsNinety RA patients with positive anti‐cyclic citrullinated antibodies (anti‐CCP) and 90 healthy blood donors (HBD) were studied. aCL and aβ2GPI of isotype IgG, IgA and IgM were detected by ELISA.ResultThe frequency of antiphopholipid antibodies (aPL) (aCL and/or aβ2GPI) was significantly higher in patients with RA than in HBD (35.5% vs 11.1%, P = .0001). The frequencies of aCL and aβ2GPI were significantly higher in patients than in healthy subjects (15.5% vs 5.5%, P = .04 and 32.2% vs 11.1%, P = .0005 respectively). aβ2GPI‐IgA were significantly more frequent in patients than in the control group (26.7% vs 7.8%, P = .0007). In patients, aβ2GPI‐IgA were significantly more frequent than aβ2GPI‐IgG (26.7% vs. 6.7%, P = .0003) and aβ2GPI‐IgM (26.7% vs 5.6%, P = .0001). In RA patients, the frequency of aβ2GPI was significantly higher than that of aCL (32.2% vs 15.5%, P = .008). aβ2GPI‐IgA was significantly more frequent than aCL‐IgA (26.7% vs 4.4%, P = .00005). The average titer of anti‐CCP in aPL positive patients was significantly higher than in aPL negative patients (170.6 ± 50 RU/mL vs 147.7 ± 51 RU/mL, P = .04). Significant correlation was found between aβ2GPI‐IgA and anti‐CCP (r = .235, P = .026).ConclusionsaPL and particularly aβ2GPI‐IgA are frequent in RA and are correlated with anti‐CCP.

Peripheral CD4CD8 Double Positive T Cells with a Distinct Helper Cytokine Profile Are Increased in Rheumatoid Arthritis

Peripheral CD4CD8 double positive (DP) T cells have been reported to play a role in several autoimmune diseases, virus infections and cancer. In rheumatoid arthritis (RA), both CD4 and CD8 single positive (SP) T cells are known to be involved in the pathogenesis, but the role of peripheral CD4CD8 DP T cells has not been investigated in detail. Anti cyclic citrullinated antibodies (ACPA) positive and ACPA negative RA patients, patients with systemic lupus erythematodes (SLE) and age matched healthy donors (HD) were enrolled in the analysis. The frequencies and phenotype of DP T cells in PBMC were investigated. In addition, DP T cells were quantified in biopsies from rheumatoid synovium. After in vitro restimulation, the cytokine production of DP T cells was investigated in cultures of PBMC. CMV specific cytokine secretion as well as proliferation was analyzed following antigen specific restimulation after an appropriate culture duration. DP T cells were found more frequently in RA patients than in healthy controls or patients with SLE. These DP T cells express αβ TCRs, are of a memory phenotype and share features of both CD4 as well as CD8 SP T cells. Importantly, DP T cells were found to also be present in the rheumatoid synovium. Further characterization of DP T cells from RA patients revealed increased production of IL-21 and IL-4, implying a possible role as T helper cells. In addition, DP T cells in RA seem to contribute to the inflammatory process, because they produce significantly more IFNγ than counterparts from HD and are increased in CMV+ RA patients. Given their capacity to produce a variety of cytokines (IL4, IL21 and IFNγ), their association with ACPA positive RA and their presence in the synovium, we suggest an important role of double positive T cells in the pathogenesis of rheumatoid arthritis.

Ultrasound Assessment for the Rapid Classification of Early Arthritis Patients

ObjectiveThe present study aimed to assess the role of ultrasound (US) in the rapid classification of early rheumatoid arthritis (RA) by investigating whether the US features of inflammation and bone...

Sarcoidois: is it only a mimicker of primary rheumatic disease? A single center experience

Sarcoidosis is known as a T helper 1 lymphocyte (Th1-Ly) mediated disease which can imitate or sometimes accompany many primary rheumatic diseases. The purpose of this study is to share the clinical, demographic and laboratory data of patients presenting with rheumatologic manifestations and diagnosed with sarcoidosis. A total of 42 patients (10 men) were included in the study. The patients were admitted to the rheumatology outpatient clinic for the first time with different rheumatic complaints between November 2011 and May 2013 and were diagnosed with sarcoidosis after relevant tests. Clinical, demographic, laboratory, radiological and histological data of these patients were collected during the 18-month follow-up period and then analyzed. Mean patient age was 45.2 years (20-70 years) and mean duration of disease was 3.5 years (1 month-25 years). Evaluation of system and organ involvement revealed that 20 (47.6%) patients had erythema nodosum, 3 (7.1%) had uveitis, 1 (2.3%) had myositis, 1 (2.3%) had neurosarcoidosis, 32 (76.2%) had arthritis and 40 (95.2%) had arthralgia. Of the 32 patients with arthritis, 28 (87.5%) had involvement of the ankle, 3 (9.4%) had involvement of the knee and 1 (3.2%) had involvement of the wrist. No patient had cardiac involvement. Thoracic computed tomography scan showed stage 1, 2, 3 and 4 sarcoidosis in 12 (28.5%), 22 (52.4%), 4 (9.5%) and 4 (9.5%) patients, respectively. Histopathology of sarcoidosis was verified by endobronchial ultrasound, mediastinoscopy and skin and axillary biopsy of lymphadenopathies, which revealed noncaseating granulomas. Laboratory tests showed elevated serum angiotensin-converting enzyme in 15 (35.7%) patients, elevated serum calcium level in 6 (14.2%) patients and elevated serum 1,25-dihydroxyvitamin D concentrations in 2 (4.7%) patients. Serological tests showed antinuclear antibody positivity in 12 (28.5%) patients, rheumatoid factor positivity in 7 (16.6%) patients and anticyclic citrullinated antibody positivity in 2 (4.8%) patients. Sarcoidosis can imitate or accompany many primary rheumatic diseases. Sarcoidosis should be considered not simply as an imitator but as a primary rheumatic pathology mediated by Th1-Ly. New studies are warranted on this subject.

Characteristics of Sjogren's syndrome in rheumatoid arthritis

To compare features of SS in RA with primary SS and RA without SS. Patients hospitalized between January 2007 and December 2010 were retrospectively studied. Seventy-four cases of overlap RA and SS (RA/SS) among 509 cases of RA were identified. Cases of SS (n = 187) detected during the same period acted as controls. Among those with RA/SS, there were 46 cases of RA-onset SS and 12 cases of SS-onset RA. Sixteen patients had simultaneous-onset RA and SS. Compared with RA without SS, RA/SS patients had more severe arthritis; a higher incidence of haematological abnormality, fever and rash; and a higher frequency of RF, ANAs and anti-SSA and anti-SSB antibodies (P < 0.05). Compared with primary SS, RA/SS patients were older, had more severe arthritis, anaemia and lung involvement; a lower incidence of fever, rash, leucopenia, thrombocytopenia and hyperthyroidism; and a higher frequency of RF, anti-keratin antibody, anti-perinuclear factor and anti-cyclic citrullinated antibodies (P < 0.05). Compared with RA and primary SS, RA/SS patients had higher disease activity scores of both RA and SS. RA/SS patients have distinctive features, with more complications and systemic involvement. In addition, disease activity is higher in RA/SS.

Diagnostic value of Anti-CCP antibodies compared with Rheumatoid factor in Rheumatoid arthritis patients.

Citrullinated proteins have been discovered in the joints of patients with rheumatoid arthritis but not in other forms of joint disease. The citrullinated proteins in the joints correspond to the presence of the citrulline antibodies in the blood and suggest a possible role for these antibodies in the development of rheumatoid arthritis. The present study assessed the recent diagnostic value of anti-cyclic citrullinated antibodies (CCP) compared with rheumatoid factor (RF) in patients with rheumatoid arthritis. One hundred blood samples were collected from RA patients and thirty from apparently healthy group. Sera from each subject were tested for anti- CCP and RF by enzyme linked immunosorbent assay (ELISA). The majority of patients were females (84%), with a female: male ratio 5.2:1. The results indicated that anti-CCP postivity for RA patients was (69%) when compared with the healthy group (0.0%), which was highly significant in RA in comparison with control groups (P<0.001). The current study revealed that the sensitivity and specificity of Anti-CCP appeared the highest (69%) in comparison with low (47%) sensitivity for RF. Moreover, the specificity of Anti-CCP was very high (100%), while the specificity of RF was high (90%).

Association of anticyclic citrullinated peptide antibodies with extra-articular manifestations, gender, and tabagism in rheumatoid arthritis patients from southern Brazil

Gender and environmental factors are known to influence the clinical heterogeneity and outcome of rheumatoid arthritis (RA). Some variables have been suggested to be associated with the severity of the disease, which can be of great value in the correct management of RA patients. The purpose of this study was to investigate the associations among anticyclic citrullinated antibody (anti-CCP2) positivity, extra-articular manifestations (EAM), gender, and tobacco exposure in a Brazilian RA population. We performed a transversal study comprising 156 RA patients which were investigated for EAM, functional class, presence of anti-CCP2, and IgM rheumatoid factor (IgM-RF). The determination of anti-CCP2 was performed using enzyme immunoassay (ELISA) kits and IgM-RF by latex agglutination test. Clinical and demographical data were obtained through review of charts. Anti-CCP positivity intensity was directly correlated with tobacco smoking, sex, and the development of rheumatoid nodules. Intense anti-CCP2 reaction was 19.8-fold higher in females vs. males, 2.7-fold higher in tobacco vs. non-tobacco users, 7.7-fold higher in female vs. male tobacco users, and 5.15-fold higher in patients with rheumatoid nodules. Tobacco smoking, gender, and rheumatoid nodules are significantly correlated with anti-CCP2 positivity in Brazilian RA patients.

Contribution of HLA-DRB1*04 alleles and anti-cyclic citrullinated antibodies to development of resistance to disease-modifying antirheumatic drugs in early rheumatoid arthritis

This study was intended to evaluate HLA-DRB1 alleles and antibodies against anti-cyclic citrullinated peptides (anti-CCP Abs) for their value in predicting patient responses to treatment with disease-modifying antirheumatic drugs (DMARDs) in early rheumatoid arthritis (RA). The subjects were 124 Japanese patients who had received their first treatment with DMARDs, usually methotrexate, within 1 year of disease onset and who had been followed-up for 2 years subsequently. Approximately 40% of patients developed DMARD resistance and accordingly required anti-tumor necrosis factor α (TNFα) therapy during the 2-year period. DMARD resistance was strongly associated with the carriage of SE-positive HLA-DRB1*04 alleles, especially the *0405 allele (OR, 3.92; 95%CI, 1.83-8.41; p = 0.0003). In contrast, the SE-positive allele HLA-DRB1*0101 was less potent in contributing to DMARD resistance. The rate of anti-CCP Ab-positive patients was significantly higher in the DMARD-resistant group (OR, 6.62; 95%CI, 1.45-30.24; p = 0.008). Multivariate logistic regression analysis confirmed the strong association of DMARD resistance with the presence of SE-positive *04 alleles (OR, 2.89; 95%CI, 1.28-6.53; p = 0.011) and anti-CCP Abs (OR, 6.31; 95%CI, 1.23-32.34; p = 0.027), yielding an area under the receiver operating characteristic curve of 0.76 (95% CI, 0.68-0.84; p = 0.000). After stratification, the highest rate of DMARD resistance was observed in patients having both SE-positive *04 alleles and anti-CCP Abs. These observations show that the presence of SE-positive *04 alleles in combination with anti-CCP Abs is the strongest predictor for development of DMARD resistance and eventual need of anti-TNFα agents in patients with early RA.

Accelerated Cutaneous Nodulosis Associated with Aromatase Inhibitor Therapy in a Patient with Rheumatoid Arthritis: Figure 1.

To the Editor: Aromatase inhibitors have become widely used for the treatment of breast cancer. We describe a patient with rheumatoid arthritis (RA) treated with the aromatase inhibitor letrozole who subsequently developed accelerated cutaneous nodulosis. A 71-year-old woman with a 21-year history of RA had established care at the University of California San Diego 7 years after her initial diagnosis, where she was noted to have a symmetric inflammatory arthritis of the metacarpophalangeal and proximal interphalangeal joints, wrists, elbows, and knees with an elevated titer of rheumatoid factor (RF) and anti-cyclic citrullinated antibody. She was given sulfasalazine and eventually methotrexate (MTX). However, because nodules appeared on the fingers and pressure areas such as the Achilles tendon, leflunomide was substituted for MTX. This was eventually discontinued due to inactive disease. In December 2005, when she was no longer taking MTX or leflunomide, a chest radiograph disclosed lesions in the breast and lung suggestive of metastatic breast cancer. In March 2006, she started the aromatase inhibitor letrozole 2.5 mg daily. In April 2006, a mastectomy and sentinel node biopsy revealed an invasive, mixed ductal … Address reprint requests to Dr. Chao; E-mail: J5Chao{at}ucsd.edu

A simultaneous onset of organizing pneumonia and rheumatoid arthritis, along with a review of the literature

Organizing pneumonia (OP) is a specific type of interstitial pneumonia that has been noted as one of the pulmonary manifestations during the course of rheumatoid arthritis (RA). In this study, we report a case with a simultaneous development of OP and RA. The patient presented with concurrent flu-like symptoms and arthralgia of multiple joints, and antibiotic therapy was not effective. The rheumatoid factor (RF) and anti-cyclic citrullinated antibodies were both high. Multiple air-space opacities on chest radiographs and bilateral peripheral consolidations on high-resolution computed tomography films were evident. The histology of transbronchial lung biopsy samples was characterized by intra-alveolar buds of granulation tissue consisting of intermixed myofibroblasts and connective tissues. Treatment with prednisolone induced a complete recovery from OP without relapses. Our review of previous reports about RA-associated OP (RA-OP) suggested that the high titer of RF and increased disease activity of RA indicate a great risk of developing OP. This condition may represent a lung's reaction in the RA-associated inflammatory and/or immune process. We should be aware of RA-OP cases in which pulmonary manifestations precede articular symptoms. In these cases, respiratory manifestations are the main evidence of RA activity. In most cases of steroid-resistant RA-OP, the use of immunosuppressants was effective. Since OP may progress to fibrotic lung disease during the course of RA, we may consider performing a second lung biopsy for steroid-resistant patients, even if they have once been diagnosed as OP.

Outcome of patients with arthritis and parvovirus B19 DNA in synovial membranes

To investigate the follow-up of the 17 patients during the period of 1995-2001 of the outpatient Clinic for Rheumatology at the University Hospital of Zurich with arthritis and the presence of parvovirus B19 DNA demonstrated by PCR in synovial biopsies. Seventeen patients of 163 with arthritis, which were routinely examined by needle arthroscopy during 1995-2001 with a positive parvovirus B19 DNA by PCR of synovial biopsy were reevaluated. Investigations included medical history, clinical examination and blood tests. Joint fluid was taken on patients with joint effusion. The observation period of the 17 patients (F:M = 11:6) was 2-8 years (Ø = 6.5 years). In 8 of 17 patients the arthritis could not be classified neither at entry nor during the follow up of the study. The arthritis could be diagnosed in six patients early in the onset of the disease and included three cases of lyme arthritis of the knee joint, two cases with arthritis following a gastrointestinal infection (one with Salmonella typhimurium--positive faecal test--and the other one with a culture negative agent), one patient probably had an infection-associated arthritis after a gastrointestinal infection with Entamöeba histolytica (Schirmer et al. in Rheumatol Int 18:37-38, 1998; Kasliwal in Am J Proctol Gastroenterol Colon Rectal Surg 32:12, 16, 28, 1981; Haslock and Wright in J R Coll Phys Lond 8:1554-162, 1974; Than-Saw et al. in Trop Geogr Med 44:355-358, 1992) with remission after antibiotic therapy. After a disease course of 9 months one patient could be classified as rheumatoid arthritis in the presence of anti-cyclic citrullinated antibodies but lack of rheumatoid factor. One patient with polyarthritis developed psoriasis of the skin 22 months later. From the nine patients with unclassified arthritis 4 (45%) got into complete remission with no symptoms or signs of joint inflammation after a disease course of 9-45 months, whereas 5 (55%) still demonstrate active non erosive arthritis (disease duration between 3 and 10 years). The presence of parvovirus B19 DNA in synovial tissue of patients with joint inflammation does not allow the diagnosis of parvovirus induced arthritis. If the arthritis remains unclassified and without erosions over time a virus associated aetiology may be assumed. However, no definitive diagnosis is possible even in the presence of parvovirus B19 DNA in synovial tissue.

The Clinical Application of Anti-CCP in Rheumatoid Arthritis and Other Rheumatic Diseases

Rheumatoid arthritis (RA) is a common rheumatic disease in Caucasians and in other ethnic groups. Diagnosis is mainly based on clinical features. Before 1998, the only serological laboratory test that could contribute to the diagnosis was that for rheumatoid factor (RF). The disease activity markers for the evaluation of clinical symptoms or treatment outcome were the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). As a matter of fact, the diagnosis of early RA is quite impossible, as the clinical criteria are insufficient at the beginning stage of the disease. In 1998, Schelleken reported that a high percentage of RA patients had a specific antibody that could interact with a synthetic peptide which contained the amino acid citrulline. The high specificity (98%) for RA of this new serological marker, anti-cyclic citrullinated antibody (anti-CCP antibody), can be detected early in RA, before the typical clinical features appear. The presence or absence of this antibody can easily distinguish other rheumatic diseases from RA. Additionally, the titer of anti-CCP can be used to predict the prognosis and treatment outcome after DMARDs or biological therapy. Therefore, with improvement of sensitivity, the anti-CCP antibody will be widely used as a routine laboratory test in the clinical practice for RA.

Laboratory assessment in musculoskeletal disorders.

Autoimmune-mediated musculoskeletal disorders feature the presence and pathogenic role of circulating autoantibodies and autoreactive T cells. Determination of these autoantibodies provides crucial information to establish the diagnosis of these diseases. In addition, the determination of these antibodies may have prognostic value or may be used to monitor response to treatment or to predict relapse of disease. We first address the main characteristics of several autoantibody assays that are considered to be clinically most relevant. These include rheumatoid factor (RF), anti-cyclic citrullinated antibody (anti-CCP), antinuclear autoantibodies (ANA), anti-double-stranded DNA antibodies, antibodies to extractable nuclear antigens (ENA), and antineutrophil cytoplasmic autoantibodies (ANCA). Subsequently we provide a brief overview of the most important musculoskeletal disorders, such as rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis/CREST, polymyositis/dermatomyositis and vasculitis. Our main goal was to address the role of the determination of autoantibodies in the diagnosis and follow-up of musculoskeletal disorders.