Anti-cyclic citrullinated peptide antibody in systemic sclerosis

OBJECTIVES:To determine if anti-cyclic citrullinated peptide (anti-CCP) antibody titers can distinguish the overlap syndrome of systemic sclerosis and rheumatoid arthritis (SSc-RA) in patients with systemic sclerosis (SSc) and to investigate the clinical significance of anti-CCP antibodies in SSc.METHODS:Serum levels of anti-CCP antibodies were measured by enzyme-linked immunosorbent assay in 159 outpatients: 114 with SSc, 14 with rheumatoid arthritis, 7 with SSc-RA overlap syndrome, and 24 with Sj?gren's syndrome. In patients with SSc and SSc-RA, we also measured serum levels of matrix metalloproteinase-3 and anti-agalactosyl IgG antibody.RESULTS:Elevated serum levels of anti-CCP antibodies were observed in 3 of 114 patients (2.6%) with SSc, 9 of 14 patients (64%) with RA, 6 of 7 patients (86%) with SSc-RA, and only 1 of 24 patients (4.2%) with SjS. In patients with SSc-RA, serum anti-CCP antibody levels were significantly higher than those seen in SSc (p<0.001). The sensitivity, specificity, and predictive values of elevated anti-CCP titers for SSc-RA were higher than either matrix metalloproteinase-3 and anti-agalactosyl IgG antibodies as markers. In addition, almost all SSc-RA and SSc patients with elevated serum levels of anti-CCP antibodies exhibited arthralgias and interstitial pneumonia.CONCLUSIONS:Anti-CCP antibody titers are a reliable marker of SSc-RA facilitating its distinction from SSc alone.     

Anticitrulline peptide antibodies (CCP3) in leprosy sera: a negative association

Anticyclic citrullinated peptide antibodies (anti-CCP) have been described almost exclusively in patients with rheumatoid arthritis. Recently, these autoantibodies have been found in patients with active tuberculosis. Leprosy is another mycobacterial disease where the presence of autoantibodies has been described by several authors. In this study, 64 patients with leprosy (32 paucibacillary and 32 multibacillary forms of the disease) were evaluated and only 2 patients were positive for the presence of anti-CCP. The low frequency of anti-CCP in leprosy sera demonstrated in our study illustrates the high specificity of anti-CCP for the diagnosis of rheumatoid arthritis.     

Anti-cyclic citrullinated peptide antibody in rheumatoid arthritis: relation with disease aggressiveness

OBJECTIVES: To analyse the value of the anti-cyclic citrullinated peptide antibody (anti-CCP) in patients with rheumatoid arthritis (RA) as a prognostic factor, as well as its relationship with disease activity. METHODS: A cross-sectional study was made on 89 patients with RA. The following values were assessed: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-CCP, Disease Activity Score 28 (DAS 28), Modified Health Assessment Questionnaire score (M-HAQ) and simplified radiologic score of Sharp/Van der Heijde (SENS: simple erosion narrowing score). RESULTS: Sixty-four percent of the patients were anti-CCP positive, from which 36.8% were negative for RF. Among negative RF patients, 48.3% had anti-CCP antibody. The average value of DAS 28 in anti-CCP positive patients was 4.31 (SD 1.27) compared to 3.30 (SD 1.55) for anti-CCP negative (p 200 U/ml) had higher SENS (p < 0.05). There was no correlation between M-HAQ and anti-CCP. CONCLUSION: Prevalence of anti-CCP was higher among patients with higher activity. Patients with higher levels of anti-CCP antibody had more aggressive disease, with greater activity (elevated values in DAS 28 and CRP) and more severe radiological damage (more erosions and higher radiological damage, SENS).     

值得关注的非结核分枝杆菌——耐热分枝杆菌

耐热分枝杆菌(Mycobacterium thermoresistible)是非结核分枝杆菌(non-tuberculous mycobacteria,NTM)中的一种快速生长型分枝杆菌,1966年日本学者TsukaTnura[1]第1次从土壤中分离出,后有人在呼吸道感染的动物体内分离出这种细菌[2].     

Anti-cyclic citrullinated peptide antibody determination in synovial fluid of psoriatic arthritis

OBJECTIVE: To assess the role of anti-CCP antibodies in synovial fluid (SF) of psoriatic arthritis (PsA) patients by analysing their association with different clinical patterns of the disease. METHODS: Seventy-five patients with a knee-joint effusion were studied, including 31 PsA patients, 29 rheumatoid arthritis (RA) and 15 osteoarthritis (OA) patients. SF and paired serum samples were stored at -70 degrees C until IgG anti-CCP and total IgG determination. The pattern of PsA articular involvement was defined as mono-, oligo-, polyarticular or axial. RESULTS: Lower levels of IgG anti-CCP antibodies in SF (p < 0.01) and serum (p < 0.005) were found in PsA respect to RA patients without difference with OA. We found a higher SF/serum ratio for anti-CCP compared to the SF/serum ratio for total IgG in PsA (p < 0.0005) as well as in RA and OA. The correction of anti-CCP concentration in SF as IgG anti-CCP (unit) / total IgG revealed lower (p < 0.002) values in PsA patients with respect to RA patients. In PsA group, values of anti-CCP antibodies, SF/serum ratio of anti-CCP and anti-CCP/IgG above the cut-off were found in 5, 6 and 2 SF samples respectively. The presence or absence of anti-CCP antibodies did not discriminate a particular clinical subset. CONCLUSIONS: In conclusion, strengthening the concept of local production of anti-CCP antibodies within the joint space, our results suggest that anti-CCP antibody detection in SF should take into account corrections such as total amount of corresponding immunoglobulin or SF/serum ratio. In our study, the presence or absence of anti-CCP antibodies did not discriminate a particular clinical subset, but further longitudinal studies are required to clarify the clinical role of anti-CCP in PsA.     

Anti-cyclic citrullinated peptide antibody isotypes in rheumatoid arthritis: association with disease duration, rheumatoid factor production and the presence of shared epitope

OBJECTIVE: Anti-cyclic citrullinated peptide (anti-CCP) antibodies of IgG isotype are specific diagnostic markers of rheumatoid arthritis (RA). Recent evidence also points to their direct involvement in the pathophysiology. Little information is available, however, regarding the isotype distribution of anti-CCP antibodies and the characteristics of IgA and IgM anti-CCP. METHODS: IgG, IgA and IgM anti-CCP2 and rheumatoid factor (RF) levels were measured in the sera of 119 RA patients and 118 controls, including patients with other rheumatic diseases and healthy subjects. We analyzed the diagnostic performance of IgA and IgM anti-CCP2 antibodies and their relationship with IgG anti-CCP2, RFs, disease duration and the presence of HLA-DRB1 shared epitope (SE) alleles. RESULTS: Patients with RA had significantly higher serum IgA and IgM anti-CCP2 antibody levels than healthy subjects and patients with other rheumatic diseases (p<0.0001). IgG, IgA and IgM anti-CCP2 antibodies were present in 74.8%, 52.9% and 44.5% of RA patients, and their diagnostic specificity was 95.8%, 95.8% and 91.6%, respectively. The presence of anti-CCP2 antibodies was significantly associated with SE alleles (p=0.03). The frequency of IgM anti-CCP2 positivity was lower in longstanding disease compared to early RA (p=0.03). CONCLUSION: IgA and IgM anti-CCP2 antibodies are present in RA patients, and they are similarly specific for RA as IgG anti-CCP2. The higher frequency of IgM anti-CCP2 antibodies in early RA suggests that they are mostly generated during the first phase of immune response; nonetheless, their production seems to be sustained in some patients. Further analysis of IgM and IgA anti-CCP2 antibodies may provide insights into the pathogenesis of RA.     

抗环瓜氨酸肽抗体与类风湿关节炎疾病活动及骨侵蚀关系的研究

目的 探讨类风湿关节炎(RA)患者抗环瓜氨酸肽(CCP)抗体、类风湿因子(RF)与疾病活动度、功能状态及骨侵蚀的关系.方法 入选RA患者218例.健康对照41名,ELISA法检测抗CCP抗体,乳胶凝集法检测RF,同时记录RA患者的临床资料.分析抗CCP抗体、RF阳性和阴性患者中疾病活动指数28(DAS28)、健康评估问卷(HAQ)的变化,并探讨其中124例病程>2年的患者抗CCP抗体、RF与骨侵蚀的关系.结果 RA患者中抗CCP抗体阳性率为76%,RF阳性率为71%.DAS28评分在抗CCP抗体、RF阳性患者明显高于阴性患者(P＜0.05);抗CCP抗体浓度与DAS28评分相关(r=0.385,P=0.032);RF滴度与DAS28评分相关(r=0.141,P=0.037);红细胞沉降率(ESR)、C反应蛋白(CRP)及HAQ评分在抗CCP抗体、RF阳性和阴性患者之间的差异无统计学意义(P＞0.05).抗CCP抗体阳性患者更易出现骨侵蚀,与阴性患者相比,差异有统计学意义(P＜0.05).RF阳性和阴性患者之间骨侵蚀的差异无统计学意义.结论 抗CCP抗体、RF与疾病活动度相关,抗CCP抗体阳性患者更易出现骨侵蚀,但RF与骨侵蚀未表现出相关性.     

Pulmonary infections associated with non-tuberculous mycobacteria in immunocompetent patients

A decline in the prevalence of tuberculosis in the developed world over the past several years has been accompanied by an increase in the rate of mycobacterial disease caused by non-tuberculous mycobacteria. However, it is still unclear whether there is a real increase in prevalence or whether non-tuberculous mycobacterial disease is being recognised more frequently by clinicians in a variety of clinical settings, thus enhancing the competence of microbiologists to detect the more unusual and fastidious mycobacteria. The introduction of liquid media for isolation of mycobacteria coupled with more accurate methods for identification have allowed several new species associated with human disease to be recognised. Despite this progress, several issues related to non-tuberculous mycobacterial infections need to be addressed, including the timely and reliable identification of isolates, standardisation and clinical evaluation of susceptibility testing, and capability to distinguish disease-causing isolates from contaminant or saprophytic species. Treatment regimens for non-tuberculous mycobacterial disease are still largely undefined and outcome remains disappointing despite substantial upgrading in laboratory diagnosis and the availability of new antimicrobials. Treatment success is impaired by the long duration of regimens, side-effects, and drug interactions, which prevent patients from full compliance. We discuss the epidemiological features, clinical syndromes, and developments in the investigation, prevention, and treatment of pulmonary non-tuberculous mycobacterial infections.     

Anti-cyclic citrullinated peptide antibodies in scleroderma patients

Anti-CCP (cyclic citrullinated peptide) is considered the most useful laboratory tool in the diagnosis of rheumatoid arthritis (RA). Some authors have also found this autoantibody in patients with scleroderma (SSc). The study aimed to investigate the prevalence of anti-CCP antibodies in SSc patients from Southern Brazil and their association with clinical and serological profile of the disease. We studied 76 patients with SSc and 100 healthy volunteers for presence of anti-CCP. SSc patients charts were reviewed for clinical and laboratory data. In the SSc group, the diffuse form was present in 20.5%; 62.8% had the limited form; 14.1% had overlap with systemic lupus or polymyositis and 2.5% had SSc sine scleroderma. Anti-CCP was found in nine of 78 (11.5%) SSc patients and in one of 100 healthy volunteers (p = 0.0054). No relationship was found with arthritis, skin Rodnan m score, esophageal dysmotility, myocarditis, pulmonary hypertension and lung fibrosis. Positive association was observed with arthralgias (p = 0.02). Also, no relationship was noted with the presence of anti-centromere antibodies, anti-Scl-70, anti-RNP or rheumatoid factor. Anti-CCP are more common in SSc patients than in controls. Arthralgias but not arthritis or rheumatoid factor are more frequent in anti-CCP positive patients.     

Anti-cyclic citrullinated peptide antibody predicts functional disability in patients with rheumatoid arthritis in a large prospective observational cohort in Japan

To clarify the clinical significance of anti-cyclic citrullinated peptide antibody (anti-CCP) in the long-term outcome of RA, we established a large observational cohort of RA patients (IORRA) in our institute beginning in 2000. Essentially all RA patients who consulted our institute were registered, and clinical parameters, including disease activity and drug use, were assessed biannually based on patient reports, physician examinations, and laboratory data. In the third phase (October 2001) of the IORRA survey, anti-CCP levels were measured in 1,226 RA patients. In a cross-sectional analysis, clinical variables were compared in anti-CCP-positive versus -negative patients and in RF-positive versus -negative patients. In a longitudinal analysis, subsequent progression of disability was analyzed in anti-CCP-positive versus -negative and in RF-positive versus -negative patients. A verified Japanese version of the Health Assessment Questionnaire (J-HAQ) was used to measure functional disability. In the cross-sectional analysis, anti-CCP-positive patients (84.2%) had a significantly longer disease duration and higher disease activity score and more frequently used corticosteroids and methotrexate compared to anti-CCP-negative patients statistically. Similar phenomena were noted between RF-positive and -negative patients. In contrast, the longitudinal analysis revealed that J-HAQ slopes—a measure of progression of functional disability—were strongly associated with anti-CCP positivity but not with RF positivity. In a linear regression model, J-HAQ scores significantly worsened in anti-CCP-positive patients compared to anti-CCP-negative patients at the third year (annual progression 0.0317, P = 0.001) and the fifth year (annual progression 0.0199, P = 0.0012); however, J-HAQ progression was not influenced by RF status. Anti-CCP is a better predictive and discriminative marker for progression of disability in the long-term outcome of RA patients compared to RF.     

Ancillary treatment of patients with lung disease due to non-tuberculous mycobacteria: a narrative review

Background and ObjectiveNon-tuberculous mycobacterial lung disease (NTM-LD) manifests with bronchiectasis, inflammatory bronchiolitis, nodules, and/or cavitation. Bronchiectasis is characterized by permanently dilated airways wherein mucus accumulates, creating a vicious cycle of chronic injurious inflammation and recurrent infections. While antibiotics are an important part of the treatment of NTM-LD, airway clearance techniques to mitigate this pathogenic mechanism of bronchiectasis as well as other ancillary measures are also important components of NTM-LD treatment. The objective of this contemporaneous Narrative Review is to emphasize the importance of such ancillary measures.MethodsWe searched PubMed for the key words of “airway clearance”, “pulmonary rehabilitation”, “nutrition”, “swallowing dysfunction”, “gastroesophageal reflux”, “vestibular dysfunction”, or “cochlear dysfunction” with that of “non-tuberculous mycobacterial lung disease”, “bronchiectasis”, or “respiratory disease”. The bibliographies of identified articles were further searched for relevant articles not previously identified. Each relevant article was reviewed by one or more of the authors and a narrative review was composed.Key Content and FindingsHerein, we discuss five ancillary treatment measures that are pertinent to patients with bronchiectasis and NTM-LD: (I) airway clearance; (II) physical and pulmonary rehabilitation; (III) nutrition; (IV) diagnosis and mitigation of swallowing dysfunction and of gastroesophageal reflux disease (GERD); and (V) minimization of vestibular and cochlear dysfunction associated with some anti-NTM drugs.ConclusionsWhile antibiotics is often the central focus of treatment of NTM-LD, given its propensity for recurrent and recalcitrant infection, other ancillary measures to break the vicious cycle of injurious inflammation and infection should also be emphasized to optimize treatment success.     

Anti-cyclic citrullinated peptide antibody is associated with radiographic erosion in rheumatoid arthritis independently of shared epitope status

Shared epitope (SE) and anti-cyclic citrullinated peptide (CCP) antibody are known to be associated with rheumatoid arthritis (RA). The authors investigated their adjusted effects on RA from Korean population. Clinical features were evaluated in 226 RA patients; 164 healthy controls were enrolled. HLA-DRB1 typing for SE was done by polymerase chain reaction. Anti-CCP antibody levels were determined by enzyme linked immunosorbent assay. Logistic regression analysis method was used for adjusted effects. SE and anti-CCP antibody were associated with RA susceptibility. Anti-CCP antibody was associated with RA susceptibility independent of SE [odds ratio, OR 179.9 (95% confidence interval, CI 40.8–792.2), P < 0.001]. Anti-CCP antibody was associated with radiographic erosive changes independent of SE or rheumatoid factor [OR 3.9 (95% CI 1.1–13.3), P = 0.032]. Anti-CCP antibody was strongly associated with RA susceptibility and radiographic erosion of RA patients, independent of SE in Korean.