The reactivities to CAP and CCP of sera from RA-overlapping CTD patients and non-RA CTD patients were measured by an in-house ELISA and absorbance values at 415nm, and the absorbance values of anti-CAP antibodies were subtracted from those of anti-CCP antibodies for each patient. Ann Rheum Dis. Arthritis Research & Therapy Abnormal Reports, SI Normal Reports | In patients with a suspected connective tissue disorder and a positive ANA titer, further testing (e.g., anti-double-stranded DNA antibodies, anti-Smith antibodies, Sjgren antibodies) should . All data were analyzed anonymously. A CCP antibodies test measures the level of these autoantibodies. Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website. The anti-cyclic citrullinated peptide (CCP) antibody is a widely used diagnostic biomarker of rheumatoid arthritis (RA). Anti-CCP antibody testing is not used to monitor RA because changes in antibody levels are not linked to changes in disease activity and patients tend to remain positive even with the reduction or disappearance of the symptoms of RA [11, 12, 13]. Antirheumatic therapy should not be initiated based solely on a positive test for CCP antibodies, and changes in treatment should not be based upon the levels of CCP antibodies. If you also test positive for RF, you likely have the disease [25]. (3,4,8,9), Compared to early serologic tests for RA including RF, several studies have demonstrated that ACPA have much improved specificity for RA. Associations between genetic factors, tobacco smoking and autoantibodies in familial and sporadic rheumatoid arthritis. ANCA positivity was further investigated with ELISA, but no known specificities, including proteinase 3 or myeloperoxidase, Cookies policy. 2012;64(4):47587. A rough guide to the disease associations of ENAs is provided in Table 1. Intravenously-administered immunoglobulin therapy is one such treatment that can in theory . If not ordering electronically, complete, print, and send a General Request (T239) with the specimen. 1. This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. They help your body recognize and fight infections. TI, SN, and KO wrote the main manuscript. (sensitivity) versus the false positive rate (1 - specificity) for various possible cutpoints of a diagnostic test. Clinical judgments were based on the following classification criteria: the American College of Rheumatology (ACR) 1997 criteria [17] or the new Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria [18] for SLE, the ACR 2012 classification criteria [19] for primary Sjgrens syndrome (pSS), the ACR 1980 classification criteria [20] for systemic sclerosis, the Bohan and Peter diagnostic criteria [21] for polymyositis/dermatomyositis, the Kasukawas criteria for mixed connective tissue disease (MCTD) [22], the Yamaguchi criteria for adult-onset Stills disease (AOSD) [23], and the Assessment in SpondyloArthritis international Society (ASAS) classification criteria for spondyloarthritis [24]. This is particularly true of laboratory tests that depend on, or directly involve the use of, antibody-based methodology. 2008;67(4):46670. it is found in Psoriatic arthritis, even leprosy, and as a false positive finding . For more information see Connective Tissue Disease Cascade. Sensitivity/specificity of citrullination dependency for predicting RA development in the population of anti-CCP positive patients with arthritis (n=39) was 96%/18%, and PPV/negative predictive value (NPV) of that was 75%/67%. Majka DS, Deane KD, Parrish LA, Lazar AA, Baron AE, Walker CW, et al. Furthermore, no reaction was seen when the structurally similar but antigenically unique control peptide was used in the assay using ChonBlock (Fig. Around 20% of RA patients who test negative for RF will test positive for anti-CCP antibodies [24]. MAMvd and LAT evaluated citrullination dependency by ELISA. Description of the definition of the follow-up length. 2017 Jun;39(4):437-446, 8. Ann Rheum Dis. How well do ACPA discriminate and predict RA in the general population: a study based on 12 590 population-representative Swedish twins. suggested that pSS patients who test positive for the anti-CCP antibody subsequently develop RA [31]. We do not aim to diagnose, treat, cure or prevent any illness or disease. Bone erosions on the hands and feet were assessed by X-ray. Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, Japan, Takeshi Iwasaki,Shuichiro Nakabo,Kosaku Murakami,Ran Nakashima,Hajime Yoshifuji,Takao Fujii,Tsuneyo Mimori&Koichiro Ohmura, Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan, Clinical Research Center, Shizuoka General Hospital, Shizuoka, Japan, The Department of Applied Genetics, The School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan, Department of Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan, Department of Clinical Immunology and Rheumatology, Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan, Department of Transfusion Medicine & Cell Therapy, Kyoto University Hospital, Kyoto, Japan, Yasuo Miura,Kimiko Yurugi&Taira Maekawa, Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands, Myrthe A. M. van Delft&Leendert A. Trouw, Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands, Department of Clinical Immunology and Rheumatology, Wakayama Medical University, Wakayama, Japan, Ijinkai Takeda General Hospital, Kyoto, Japan, You can also search for this author in . Despite its high specificity, previous studies reported that 510% of non-RA connective tissue disease (CTD) patients tested positive for the anti-CCP antibody [1, 2]. Antibodies are . Springer Nature. Your doctor will also order ESR and CRP tests that measure inflammation. is currently the most widely used anti-citrullinated peptide assay. Arthritis Rheum. In a systematic review from 2010, it was found that false positivity can also occur in chronic . The frequency of antibodies against cyclic citrullinated peptides and rheumatoid factor in healthy population: a field study of rheumatoid arthritis from northern Turkey. 2006;65(8):11102. Anti-Cyclic Citrullinated Peptide Antibody - Medscape 1 Introduction. Anti-Sm antibody binds to a protein that is attached to DNA. Positive CCP antibody?: Hi All- I just discovered I - NRAS TI and SN analyzed the data. The existence of the anti-CCP antibody in non-RA patients, such as those with autoimmune hepatitis [14], tuberculosis [15], and systemic lupus erythematosus (SLE) [16], is not dependent on citrullination. We are dedicated to providing the most scientifically valid, unbiased, and comprehensive information on any given topic. The isotype and IgG subclass distribution of anti-carbamylated protein antibodies in rheumatoid arthritis patients. 1997;40(9):1725. Anti-cyclic citrullinated peptide antibodies in type 1 autoimmune hepatitis. Primary Biliary cirrhosis, an autoimmune disease of the biliary ducts in the liver. ACPA-positive RA is strongly associated with certain HLA-DRB1 alleles that carry specific amino acid sequences, the so-called shared epitope (SE) [7,8,9,10,11]. 2010;49(12):2298304. Clinical Utility of Common Serum Rheumatologic Tests | AAFP Your email address will not be published. Different patterns of associations with anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis in the extended major histocompatibility complex region. The wells are then washed to remove unbound serum constituents, and horse radish peroxidase-labeled goat anti-human IgG antibody is added. Epstein-Barr Virus Laboratory Testing - Centers for Disease Control and 1). M Hashimoto: Received a research and/or speaker fee from Bristol-Myers, Eisai, Eli Lilly, and Tanabe-Mitsubishi. A positive result in combination with other signs and symptoms means you have rheumatoid arthritis. False positives are also known to happen in about 5% of tests when a person would be classified as healthy. Anti-citrullinated peptide antibodies may occur in patients with (PPTX 48 kb). Methods: The study sample included 74 subjects with respiratory symptoms, evaluated January 2008-January 2010 and found to have a positive anti-CCP antibody but no evidence for . Zhu JN, Nie LY, Lu XY, Wu HX: Meta-analysis: compared with anti-CCP and rheumatoid factor, could anti-MCV be the next biomarker in the rheumatoid arthritis classification criteria? Anti-CCP antibody titers were obtained from a retrospective chart review for 445 patients or were measured using the stored sera of 397 patients. Despite this limitation, PPV for developing RA in non-RA CTD patients (2/33, 6.1%) was markedly lower than that in healthy individuals (8296%) [3, 4] and similar to the incidence of RA complications in CTD patients in the present study ((group 1 and group 2)/group 0 in Fig. A positive anti-CCP and negative RF blood test show that you may be in the early stages of the disease or may have it in the future. Most of the time, a positive test result for antinuclear antibodies (ANA) indicates the presence of an autoimmune disorder. We also investigated the citrullination dependency of anti-CCP test results because anti-CCP antibodies may react with the non-citrullinated part of CCP peptides, which have been reported in several diseases, such as SLE [16], autoimmune hepatitis [14], and tuberculosis [15]. Kasukawa R TT, Miyawaki S, Yoshida H, Tanimoto K, Nobunaga M, Suzuki T, Takasaki Y, Tamura T. Preliminary diagnostic criteria for classification of mixed connective tissue disease: In: Kasukawa R, Sharp GC (Eds) Mixed Connective Tissue Disease and Antinuclear Antibodies. We also investigated whether the 33 patients with anti-CCP-positive CTD subsequently developed RA by asking each attending physician to confirm their fulfillment of the 1987 revised ACR criteria over time. Positive ANA -Know Common 5 causes for a positive ANA Test What Does A Positive CCP Test Mean? - MedMG Shiboski SC, Shiboski CH, Criswell L, Baer A, Challacombe S, Lanfranchi H, et al. Aletaha D, Neogi T, Silman AJ, et al: 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. 1, 7.6%). The ANA test is not specific to any one disease, but a high level of ANA can be a sign of systemic lupus erythematosus (SLE). The rheumatoid factor is not clinically significant. The anti-CCP antibodies can exist in a person's system long before they ever exhibit symptoms of RA. Despite the high specificity of the test, anti-CCP antibodies have also been observed in psoriatic arthritis. Required fields are marked *. (2) RF is an autoantibody directed against the Fc portion of immunoglobulin while ACPA are directed against peptides and proteins containing citrulline, a modified form of the amino acid arginine. Once a patient develops a positive anti-CCP, it will usually remain positive, despite remission. Testing positive for anti-CCP antibodies increases the risk of developing a more aggressive form of rheumatoid arthritis. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements. Background Many clinicians are aware that certain therapies administered to their patients can have downstream consequences in the form of clinical laboratory test interferences. Background Systemic lupus erythematosus (SLE) is a complex and challenging autoimmune disease. We believe that the most accurate information is found directly in the scientific source. 2010 Sep;62(9):2569-2581, 3. 2019 Sep;71(9):1504-1511, 9. PDF Autoantibodies related to systemic autoimmune with COVID-19 Low . Anti-cyclic citrullinated peptide (CCP) antibody and anti-cyclic arginine peptide (CAP) antibody titers. Antinuclear Antibody, Rheumatoid Factor, and Cyclic-Citrullinated Systemic lupus erythematosus manifestation following COVID-19: a case However, we could not find any significant association of citrullination dependency with erosive disease (OR=4.4 (95% CI 0.3244), p value=0.3). (2) RF is an autoantibody directed against the Fc portion of immunoglobulin while ACPA are directed against peptides and proteins containing citrulline, a modified form of the amino acid arginine. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. Anti-CCP antibodies, also called CCP antibodies, are a type of antibody called autoantibodies. Through this personalized approach, he discovered his genetic weaknesses and was able to optimize his health 10X better than he ever thought was possible. Google Scholar. Around 30% of RA patients test negative for both antibodies [24]. but is for informational and educational purposes alone. In other words, the blood test (RF) can be positive for years before the joint pain develops. Symptoms: They're extremely varied. As a result, we found significant effect on developing RA (OR Inf (95% CI 0.7-Inf), p value 0.048). K Ohmura: Received research grants and/or speakers fees from Abbvie, Actelion, Asahikasei Pharma, Astellas, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, GSK, Janssen, JB, Mitsubishi Tanabe, Nippon Kayaku, Nippon Shinyaku, Novartis, Sanofi, and Takeda. Correspondence to Patients who test positive for anti-CCP antibodies at the time of diagnosis are likely to progress more rapidly and develop more destructive forms of RA [13, 26, 11]. Hensvold AH, Frisell T, Magnusson PK, Holmdahl R, Askling J, Catrina AI. Thirty-nine out of the 62 RA-overlapping CTD patients tested positive for the anti-CCP antibody (62.9%). Rantapaa-Dahlqvist S, de Jong BA, Berglin E, Hallmans G, Wadell G, Stenlund H, et al. Semin Immunopathol. Anti-CCP antibodies target proteins in which the amino acid arginine has been converted (citrullinated) into another amino acid called citrulline. Clin Chem Lab Med. Anti-citrullinated peptide antibody assays and their role in the diagnosis of rheumatoid arthritis. Avoiding CCP False Positives in Rheumatoid Arthritis Diagnosis - Fisher Sci Significantly elevated levels of CCP antibodies may be useful to identify RA patients with erosive joint disease. The presence of anti-SCL-70 (anti-topoisomerase) antibodies is highly specific to the diagnosis of diffuse scleroderma, while the presence of anti-centromere antibodies is highly specific to the diagnosis of limited scleroderma. Based on these findings, a higher anti-CCP antibody titer and the presence of SE appear to be important factors in the development of RA, not only in the general population, but also in the anti-CCP-positive CTD population. Even patients with Rheumatoid arthritis can have a positive ANA. Anti-cyclic citrullinated peptide positivity in non-rheumatoid arthritis disease samples: citrulline-dependent or not? Antibodies protect you from disease by fighting foreign substances like viruses and bacteria. You might be able to help lower your inflammatory joint symptoms by maintaining adequate vitamin D levels, addressing any gum disease you may have, and quitting smoking. Ann Rheum Dis. Arthritis Rheum. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. The present study was performed in accordance with the Helsinki Declaration and was approved by Kyoto University Graduate School and Faculty of Medicine Ethics Committee (approval numbers: E458 and R1540). California Privacy Statement, Highest rates of false-positive RF tests were found in patients with SLE (18.3% vs. 12.7% CCP), Sjgren's syndrome (73.3% vs. 3.3% CCP), and a control group with chronic hepatitis (24.7% vs. 1.3% CCP). Development of the anti-citrullinated protein antibody repertoire prior to the onset of rheumatoid arthritis. A positive result for cyclic citrullinated peptide (CCP) antibodies indicates a high likelihood of rheumatoid arthritis (RA). In total, 842 CTD patients with a primary diagnosis that was not RA were selected from our CTD database as of December 2012. If the workup is negative, care monitoring is recommended. Arthritis Res Ther. Follow-up of primary Sjogrens syndrome patients presenting positive anti-cyclic citrullinated peptides antibody. Anti-dsDNA Test - Testing.com These antibodies are produced by the person's immune system and identify the body's tissue cells as foreign bodies and attack them. A positive result by itself does not automatically lead to a diagnosis. Information is shared for educational purposes only. Evaluating the frequency of G6PD deficiency in blood donors found the prevalence was higher in donors with a positive family history, and the potentially severe consequences of a G6 PD hemolytic crisis may argue in favor of routine G 6PD screening of male blood donors in areas with high prevalence. Fusconi M, Vannini A, Dall'Aglio AC, Pappas G, Cassani F, Ballardini G, et al. HLA-DRB1 SE and anti-CCP antibody titers may facilitate the differentiation of RA-overlapping CTD from anti-CCP-positive non-RA CTD. 2019 Oct 25;57(11):1668-1679, Cyclic citrullinated peptide (CCP) antibodies in serum are detected by binding to the wells of a commercial microtiter plate coated with synthetic CCP. If a patient tests positive for anti-CCP this is a strong indicator of RA. Ann Rheum Dis. Patients presenting with mono or pauciarticular pain of large joints with positive anti CCP antibody assay have to be investigated to rule out the possibility of early stage of tubercular arthritis before labeling them as of rheumatoid arthritis. Burgers LE, Raza K, van der Helm-van Mil AH: Window of opportunity in rheumatoid arthritis - definitions and supporting evidence: from old to new perspectives. A rheumatoid factor test measures the amount of rheumatoid factor in your blood. Joe Cohen flipped the script on conventional and alternative medicineand it worked. Currently, they are not widely used in clinical practice [22]. When you test positive for rheumatoid factor and/or another autoantibody called anti-cyclic citrullinated protein (anti-CCP) you are considered to have "seropositive rheumatoid arthritis.". Furthermore, the 2010 ACR/EULAR criteria were used to diagnose RA [26]. About 70% of RA patients test positive for anti-CCP antibodies [4, 23]. Anti CCP Antibody Assay: A Diagnostic Dilemma in Diagnosis of X-rays of the hands and feet were taken for 27 out of the 33 anti-CCP-positive CTD patients, and only one showed bone erosions (Fig. Flow chart of the classification of patients with connective tissue disease (CTD). Environmental and genetic factors in the development of anticitrullinated protein antibodies (ACPAs) and ACPA-positive rheumatoid arthritis: an epidemiological investigation in twins. A flow chart of the present study is shown in Fig. Positive results for cyclic citrullinated peptide (CCP) antibodies may occur in some patients with systemic lupus erythematosus or other autoimmune, connective tissue diseases. Effects of smoking and shared epitope on the production of anti-citrullinated peptide antibody in a Japanese adult population. Knowing the symptoms of autoimmune joint disease is of utmost importance as well. Although late RA prognosis may be linked to adverse consequences, early diagnosis has been reported to improve outcomes; notably reduced joint destruction or deformity, delayed radiologic progression, and decreased functional disability. 2017;76(1):11925. (2-4) Delayed diagnosis of RA is associated with joint erosion, destruction or deformities, poor response to treatment with ultimate increase in morbidity, and mortality.(3,4). Therefore, we excluded anti-CCP-negative samples and examined citrullination dependency. Methods . Thus, the presence of anti-CCP Abs must be interpreted as highly suggestive of a diagnosis of EORA. Therefore, we retrospectively investigated whether anti-CCP antibody-positive non-RA CTD patients developed RA and clarified whether HLA-DRB1 SE and the citrullination dependency of the anti-CCP antibody are predictive factors for RA. A large-scale association study identified multiple HLA-DRB1 alleles associated with ACPA-negative rheumatoid arthritis in Japanese subjects. The datasets generated and/or analyzed in the present study are available from the corresponding author upon reasonable request. These patients may develop RA in the future because the emergence of anti-citrullinated protein antibodies (ACPA), including the anti-CCP antibody, precedes the onset of RA [3,4,5,6]. Anti Citrullinated Antibody. If you test positive for anti-CCP antibodies, yet youre healthy and arent showing symptoms of RA, you have a much greater risk of developing the disease [19]. Antinuclear Antibody Panel (ANA Test) Antibodies are proteins made by your immune system. If you test positive for anti-CCP and are diagnosed with RA, your doctor will likely pursue a more aggressive treatment regimen. Anti CCP antibody assay may be false positive in many patients of tubercular synovitis. CCP - Overview: Cyclic Citrullinated Peptide Antibodies, IgG, Serum RACGP - Antinuclear antibody test - Australian Family Physician When faced with a positive rheumatoid factor, it's important to rule out other conditions that cause positivity. Previous studies reported that 410% of non-RA CTD patients tested positive for the anti-CCP antibody [1, 2], which is consistent with the present results. An antinuclear antibody test is a blood test that looks for certain kinds of antibodies in your body. Limitations of our study also include the following points: (1) There is a possibility that treatment for CTD suppressed RA development in anti-CCP positive patients although there were significantly less patients who had taken DMARDs compared with RA overlapping CTD (Table2). They are found in around 30-40% of patients with SLE. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Thirty-three anti-CCP-positive non-RA CTD patients were retrospectively followed up for the development of RA. The substance to which this antibody reacts is cardiolipin, so the individuals with a false-positive syphilis test actually had a form of anticardiolipin antibodies. In contrast, antinuclear antibodies often attack your body's own tissues specifically targeting each cell's nucleus. Terms and Conditions, The anti-cyclic citrullinated peptide antibody (anti-CCP) test (which has a high specificity for rheumatoid arthritis), full blood count (cytopaenias are a feature of SLE), urinalysis (haematuria and/or proteinuria may be due to renal manifestations of autoimmune disease), serum complement proteins C3 and C4 (low complement can reflect . Kakumanu P, Sobel ES, Narain S, Li Y, Akaogi J, Yamasaki Y, et al. . Overview. 2009;36(12):268290. The entire, 55-min procedure for the detection of RF and anti-CCP using a dual-target ELISA assay is shown schematically in Fig. 1987:417. Anti-cyclic citrullinated peptides (anti-CCP) are a type of autoantibody: an antibody that works against your body's normal antibodies. These include [15]: A rheumatoid factor (RF) test is commonly ordered alongside an anti-CCP test to help make a diagnosis. Treating RA early on (within 6 after symptoms begin) is crucial in preventing the disease from progressing and reducing joint damage and disability [28]. Because of this, most assays detect only IgM. These autoantibodies begin targeting and attacking otherwise healthy tissue. is a clickable link to peer-reviewed scientific studies. Your immune system normally makes antibodies to help you fight infection. Causes of MSK pain are divided into nonrheumatic and rheumatic categories. Links with this icon indicate that you are leaving the CDC website.. (10) Based on these studies, there exist a subset of patients with RA who are negative for RF and ACPA IgG (seronegative) who must be diagnosed clinically or with use of emerging diagnostic tests. Arthritis Care Res. Limitations: The presence of immune complexes may cause false-positive results due to increased non-specific binding. This ANA testing method led to an increase in rheumatology referrals for RNP . Anti-RNP. RF positivity, HLA-DRB1 SE possession, and anti-CCP antibody titers may facilitate the differentiation of anti-CCP-positive RA-overlapping CTD from anti-CCP-positive non-RA CTD. In the present study, we used the 1987 ACR criteria, not the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria [26], because the latter are not applicable to patients with symptoms that may be attributed to another disease, including CTD, and also include the anti-CCP antibody. Google Scholar. Clinical utility of anti-CCP antibodies in the differential diagnosis 2023 BioMed Central Ltd unless otherwise stated. Note that each number in parentheses [1, 2, 3, etc.] Cite 28th Dec, 2015 Seronegative Rheumatoid Arthritis | Orlando | UCF Health Although we considered an anti-CCP titer 100 to be 100, the relationship between the anti-CCP antibody titer and the risk of developing RA is supported by patients with a high ACPA level having a high score in the 2010 ACR/EULAR classification criteria of RA [26] as well as a high anti-CCP antibody titer being more strongly associated with RA in the general population [32]. CCP antibodies, also called anti-CCP antibodies, are a type of antibody called autoantibodies. These tests are slightly less accurate than tests that require blood draws that are then sent away to a lab for analysis. Rheumatoid factors are proteins produced by your immune system that can attack healthy tissue in your body. Based on his own health success, he went on to found SelfDecode, the worlds first direct-to-consumer DNA analyzer & precision health tool that utilizes AI-driven polygenic risk scoring to produce accurate insights and health recommendations. Citrullinated proteins increase their levels substantially when an inflammatory cascade is activated such as in RA [1, 2]. 2005;52(12):38138. High levels of rheumatoid factor in the blood are most often associated with autoimmune diseases, such as rheumatoid arthritis and Sjogren's syndrome. Rheumatoid Arthritis: Blood Tests for Diagnosis - Verywell Health TI and SN measured anti-CCP antibody titers by ELISA. Psoriatic arthritis, a form of arthritis that occurs in people with the skin disease psoriasis, Painful or swollen joints (especially the fingers and wrists), usually occurring on both sides of the body, Stiffness in the joints that gradually decreases throughout the day, Rheumatoid nodules, small hard lumps that develop under the skin. Tagged: Mean. Today, anti-histone antibodies are still used as a marker for systemic lupus .
causes of false positive anti ccp antibodies
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causes of false positive anti ccp antibodies