In most cases, a positive ANA test indicates that your immune system has launched a . We also analyzed citrullination dependency by mixing all anti-CCP-positive RA-overlapping CTD and non-RA CTD serum samples together and stratifying them by HLA-DR SE possession. It's also called an ANA or FANA (fluorescent antinuclear antibody) test. Long-term follow-up of patients with anti-cyclic citrullinated peptide antibody-positive connective tissue disease: a retrospective observational study including information on the HLA-DRB1 allele and citrullination dependency. Although all 60 samples tested positive for the anti-CCP antibody using a commercial ELISA kit, 5 out of 33 RA-overlapping CTD and 6 out of 27 non-RA CTD serum samples tested negative using our in-house CCP ELISA. 2019 Apr 3;5(1):e000870, 4. 2009;36(12):268290. A flow chart of the present study is shown in Fig. An ANA test detects antinuclear antibodies (ANA) in your blood. However, in 2010, the American College of Rheumatology changed their criteria for diagnosing RA to include the presence of anti-CCP antibodies [9]. These tests are slightly less accurate than tests that require blood draws that are then sent away to a lab for analysis. 2005;52(12):38138. 26460649). 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. 2017;19(1):190. Brief Summary: Due to the Covid-19 worldwide outbreak, fragile patients with immune diseases, notably rheumatoid arthritis (RA), have to be even more specifically and carefully followed-up. Manage cookies/Do not sell my data we use in the preference centre. The relationship between SE and the overlap of RA in the anti-CCP-positive CTD population is consistent with previous findings showing that SE plays a crucial role in identifying which ACPA-positive patients will ultimately develop arthritis [33]. . 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. Thus, the presence of anti-CCP Abs must be interpreted as highly suggestive of a diagnosis of EORA. CTD patients were classified based on the diagnosis of rheumatoid arthritis (RA), anti- cyclic citrullinated peptide (CCP) antibody positivity, and clinical characteristics. Antibodies protect you from disease by fighting foreign substances like viruses and bacteria. 2008;1143:26885. Bohan A, Peter JB. Furthermore, no reaction was seen when the structurally similar but antigenically unique control peptide was used in the assay using ChonBlock (Fig. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. The present study was supported in part by JSPS KAKENHI (grant no. To assess whether anti-CCP-positive CTD patients had suffered from arthritis during this time frame, the attending physicians of patients completed a questionnaire survey in September 2020. False positives are more common with RF than anti-CCP. 2009;60(1):308. Bone erosion was not observed in non-RA CTD patients but was frequently detected in RA-overlapping CTD patients (70.7%). We retrospectively investigated whether anti-CCP-positive non-RA CTD patients developed RA and attempted to identify factors that may differentiate RA-overlapping CTD from pure CTD. 2000 Jan;43(1):155-163, 7. Aliment Pharmacol Ther. Ann Rheum Dis. The positive predictive value (PPV) of anti-CCP antibody for erosive arthritis was calculated in each disease subset (n=65, groups 1, 2, and 3 with X-ray images in Fig. This is particularly true of laboratory tests that depend on, or directly involve the use of, antibody-based methodology. Arthritis Res Ther 22, 248 (2020). A CCP antibodies test measures the level of these autoantibodies. 2012;64(4):47587. Anti-CCP antibodies can be detected in the early stages of RA, even before symptoms are present. 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. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. The dependency on citrullination was evaluated by subtracting absorbance values of anti-CAP from that of anti-CCP. Interpretation. Undiagnosed Lyme can develop into chronic Lyme, cause debilitating mental health symptoms, spread throughout the body - for example, to the neurological system or the heart - and wreak havoc on patients' quality of life. Once a patient develops a positive anti-CCP, it will usually remain positive, despite remission. Until recently, rheumatoid factor (another antibody involved in RA) was the only antibody used to help diagnose the disease. In a Mayo Clinic study (see Interpretation), the false-positive rate in this subgroup was approximately 10%. 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. 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. Arthritis care & research. He belongs to the department that is financially supported by five pharmaceutical companies (Mitsubishi-Tanabe Pharma Corp., Chugai Pharmaceutical Co., Ltd., Ayumi Pharmaceutical Corp., Asahi-Kasei Pharma Corp., and UCB Japan Co., Ltd.). This test is 97% specific for RA if it is present. Our science team is put through the strictest vetting process in the health industry and we often reject applicants who have written articles for many of the largest health websites that are deemed trustworthy. However, limited information is currently available on the long-term outcomes of anti-CCP-positive non-RA CTD patients. 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). Anti-CCP-positive non-RA CTD patients rarely developed RA. Early detection of anti-CCP antibodies is crucial to properly treat the disease and stop its progression [10]. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part I): classification of paper patients by expert opinion including uncertainty appraisal. volume22, Articlenumber:248 (2020) Koichiro Ohmura. Anti-CCP antibody and other autoantibody markers can be helpful in determining which patients with rheumatoid arthritis may have benefit from treatments such as anti-tumor necrosis factor-alfa (TNFa) monoclonal antibodies. 1) (Table3). antibodies are routinely tested for by ELISA at Clinipath. Objective: To determine the frequency of anti-CCP antibodies in psoriatic arthritis and to describe the clinical characteristics of such patients. Align your health hacks with your genes for optimal health & cognitive function. Rheumatoid arthritis is an autoimmune, inflammatory disorder caused by a person's immune system mistakenly attacking and destroying healthy cells within the body. Holman, and H.R.G. Cite this article. van de Stadt LA, de Koning MH, van de Stadt RJ, Wolbink G, Dijkmans BA, Hamann D, et al. 2017;76(1):11925. This can lead to a disorder known as autoimmune vasculitis. Background: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are considered highly specific markers of rheumatoid arthritis. Low levels of anti-CCP can be found in the test results of certain patients but may not enough to produce a positive result. Approximately 70% of patients with rheumatoid arthritis are positive for Anti-CCP IgG, while only about 2% of random blood donors and disease controls subjects are positive. Interpretation in the clinical context is important. MAMvd and LAT evaluated citrullination dependency by ELISA. The presence of ANA antibodies at levels of 1:160 or higher are generally taken as a sign of lupus. Due to a higher positive rate than that in the general population (12%) [12, 13], potential differences in autoantigens between RA-overlapping CTD patients and non-RA CTD patients may be a source of concern. INOVA Diagnostics; 02/2020). Cross M, Smith E, Hoy D, et al: The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study. Twenty-seven out of 28 RA-overlapping CTD patients (96%) and 18 out of 21 (85.7%) non-RA CTD patients were citrullination-dependent (Fig. However, the target population in the present study was pSS patients who were cross-sectionally evaluated, and RA-overlapping CTD patients were not excluded when anti-CCP antibody titers were measured. (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). 1). 2021 Feb;73(2):181-193, 5. 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. Citrullination dependency was more common in patients with SE, although it was not statistically significant (p=0.11) (Fig. . 2004;50(2):3806. Evaluating patients suspected of having rheumatoid arthritis (RA), Differentiating RA from other inflammatory arthritis or connective tissue diseases. However, a large proportion of systemic sclerosis patients with the anti-CCP antibody developed erosive arthritis. To assess the reliability of the diagnosis, we evaluated all SLE patients by chart review and found that all patients fulfilled the ACR 1997 or SLICC 2012 criteria. 2014 Jul;73(7):1316-1322, 2. These include [15]: A rheumatoid factor (RF) test is commonly ordered alongside an anti-CCP test to help make a diagnosis. Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by interactions between the environment, specific genetic risk factors, and the human immune system. Duration of preclinical rheumatoid arthritis-related autoantibody positivity increases in subjects with older age at time of disease diagnosis. Arthritis Rheumatol. RMD Open. 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. Therefore, the clinical significance of the presence of the anti-CCP antibody in non-RA CTD patients remains unclear. van Delft MAM, Verheul MK, Burgers LE, Derksen V, van der Helm-van Mil AHM, van der Woude D, et al. Ann Rheum Dis. Arthritis Rheum. is currently the most widely used anti-citrullinated peptide assay. SI Abnormal Reports. Rheumatoid arthritis (RA) is a chronic, systemic inflammatory . Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. Limitations: The presence of immune complexes may cause false-positive results due to increased non-specific binding. Arthritis Rheum. RFs are used as a marker in individuals with suspected rheumatoid arthritis (RA) or other autoimmune conditions. Springer Nature. TI, SN, and KO conceived the study design. Bone erosions on the hands and feet were assessed by X-ray. Associations between genetic factors, tobacco smoking and autoantibodies in familial and sporadic rheumatoid arthritis. In some cases, patients have even died from complications . PubMedGoogle Scholar. 1) and 31 anti-CCP-positive non-RA CTD patients (group 3 in Fig. CAS Methods . Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Arthritis Rheum. Some tests can detect the presence of other types of ACPAs that the anti-CCP antibody test cant detect. Terao C, Ohmura K, Ikari K, Kawaguchi T, Takahashi M, Setoh K, et al. If CCP antibodies are found in your blood, it can be a . Anti-CCP or ACPAs is a protein and is mostly found in the joints of patients who . If you also test positive for RF, you likely have the disease [25]. In both patients with primary and SLE associated APS positive results correlate with a predisposition for arterial or venous thrombosis, foetal loss, or thrombocytopoenia. In other words, the blood test (RF) can be positive for years before the joint pain develops. When we compared clinical, serological, and genetic features between non-RA CTD and RA-overlapping CTD patients, we found not only the presence of joint symptoms, bone erosion, and RF, which were all included in the 1987 revised ACR criteria [25], but also a higher anti-CCP titer and more prevalent HLA-DRB1 SE in RA-overlapping CTD patients (Table2). Anti-cyclic citrullinated peptide (anti-CCP) antibodies are commonly found in patients with rheumatoid arthritis (RA), an autoimmune disorder that destroys the joints throughout the body [1]. Use. This immune activation destroys healthy tissue in the joints and worsens RA symptoms [3]. Google Scholar. Background/Purpose: A large multicenter healthcare system recently adopted multiplex immunoassay as an initial screen for antinuclear antibody (ANA) with confirmatory reflex testing by immunofluorescence antibody assay (IFA). Ann N Y Acad Sci. In total, 842 CTD patients with a primary diagnosis that was not RA were selected from our CTD database as of December 2012. Ann Rheum Dis. 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. One other test that can help is the anti-CCP antibody test. (4,7,9) For more information see Connective Tissue Disease Cascade. Anti-CCP antibodies are commonly found in rheumatoid arthritis patients and are thought to play a key role in the disease process. The frequency of antibodies against cyclic citrullinated peptides and rheumatoid factor in healthy population: a field study of rheumatoid arthritis from northern Turkey. Growing up, he suffered from inflammation, brain fog, fatigue, digestive problems, insomnia, anxiety, and other issues that were poorly understood in traditional healthcare. Many patients with other autoimmune disorders and inflammatory conditions test positive for rheumatoid factor but don't have rheumatoid arthritis. All authors approved the final manuscript. In addition, we calculated the association of citrullination dependency with erosive disease. However, some non-RA connective tissue disease (CTD) patients also test positive for the anti-CCP antibody and, thus, may ultimately develop RA. Anti CCP antibody assay may be false positive in many patients of tubercular synovitis. There are many infections, connective tissue diseases, malignancies, and advancing age factors associated with false-positive RF tests. Anti-cyclic citrullinated peptide (CCP) antibody and anti-cyclic arginine peptide (CAP) antibody titers. Arthritis Rheum. 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. 2010 Sep;62(9):2569-2581, 3. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. The Dangers of a Misdiagnosis. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. These antibodies are in fact present (real) but they are NOT elevated because of . Differential Diagnosis. 3.2.2. suggested that pSS patients who test positive for the anti-CCP antibody subsequently develop RA [31]. A rheumatoid factor test measures the amount of rheumatoid factor in your blood. A positive result for cyclic citrullinated peptide (CCP) antibodies may be suggestive of rheumatoid arthritis (RA) if compatible clinical features of disease are present. A plus sign next to the number [1+, 2+, etc] means that the information is found within the full scientific study rather than the abstract. van Venrooij WJ, van Beers JJ, Pruijn GJ. The entire, 55-min procedure for the detection of RF and anti-CCP using a dual-target ELISA assay is shown schematically in Fig. Verheul MK, Bohringer S, van Delft MAM, et al: Triple positivity for anti-citrullinated protein autoantibodies, rheumatoid factor, and anti-carbamylated protein antibodies conferring high specificity for rheumatoid arthritis: Implications for very early identification of at-risk individuals. Aletaha D, Neogi T, Silman AJ, et al: 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. (PPTX 45 kb), Prevalence of arthritis in anti-CCP-positive non-RA CTD patients. Ann Rheum Dis. Autoantibodies can cause disease by attacking the body's healthy cells by mistake. Anti Citrullinated Antibody. Horizontal dashed lines in a and b represent the cut-off level (=0.1) of citrullination dependency. Aggarwal R, Liao K, Nair R, Ringold S, Costenbader KH. Your email address will not be published. Furthermore, our observation period, 8.9years, was sufficiently long to assess the outcomes of the anti-CCP-positive population because the median period during which an anti-CCP-positive population developed RA was previously reported to be 4.5years [4]. 2011;63(11):322633. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition. Symptoms: They're extremely varied. 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 For some antibodies, further confirmatory testing may be required, (for example, for Jo 1 antibodies), as false positives may occur with the screening ELISA. Majka DS, Deane KD, Parrish LA, Lazar AA, Baron AE, Walker CW, et al. Anti-cyclic citrullinated peptide (CCP) antibodies are important serum markers used in the clinical diagnosis of rheumatoid arthritis (RA).However, it has been reported that CCP antibodies can be positive in various other autoimmune conditions.Multiple studies have investigated previous generations of CCP assays (CCP 1, CCP 2, CCP 3), and several have shown CCP to be a highly . Antibodies are . Arthritis Rheum. If you feel that any of our content is inaccurate, out-of-date, or otherwise questionable, please leave a comment or contact us at support@selfdecode.com. About 70% of RA patients test positive for anti-CCP antibodies [4, 23]. If you test positive for anti-CCP and are diagnosed with RA, your doctor will likely pursue a more aggressive treatment regimen. The HLA-DRB1 allele was typed using the WAKFlow system (Wakunaga Pharmaceutical, Akitakata, Japan) and the following were classified as HLA-DRB1 SE: *01:01, *01:02, *04:01, *04:04, *04:05, *04:08, *04:10, *04:13, *04:16, *10:01, *13:03, *14:02, and *14:06, as reported previously [29]. Regulation of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis: contrasting effects of HLA-DR3 and the shared epitope alleles. 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. 2007;66(4):5116. Anti-citrullinated protein antibodies (ACPAs) are autoantibodies (antibodies to an individual's own proteins) that are directed against peptides and proteins that are citrullinated.They are present in the majority of patients with rheumatoid arthritis.Clinically, cyclic citrullinated peptides (CCP) are frequently used to detect these antibodies in patient serum or plasma (then referred to as . In contrast, antinuclear antibodies often attack your body's own tissues specifically targeting each cell's nucleus. Approximately 70% of RA patients are positive for anti-CCP IgG, while only 2% of random blood donors and control subjects are positive. Arthritis Rheum. 1987:417. Antibodies are proteins that your immune system makes to fight foreign substances like viruses and bacteria. The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. 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 . It also have a specificity of around 95%, which is the percentage of results that will be . PubMed Our goal is to not have a single piece of inaccurate information on this website. Your doctor will also order ESR and CRP tests that measure inflammation. The anti-CCP antibody test measures your bodys level of antibodies that commonly target specific proteins found in the joints. 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]. There are also tests that you can take at your doctors office which only require a blood sample from a finger prick. In the present study, we focused on differences in the citrullination dependency of the anti-CCP antibody. 1). The anti-CCP test has a sensitivity of around 65-75%, which is the percentage of results that will be correctly positive. Takeshi Iwasaki and Shuichiro Nakabo contributed equally to this work. Around 30% of RA patients test negative for both antibodies [24]. The frequency of the HLA-DRB1 shared epitope (SE) and anti-CCP antibody titers were both significantly higher in anti-CCP-positive RA-overlapping CTD patients than in anti-CCP-positive non-RA CTD patients, while no significant differences were observed in citrullination dependency. The wells are then washed to remove unbound serum constituents, and horse radish peroxidase-labeled goat anti-human IgG antibody is added. Note that each number in parentheses [1, 2, 3, etc.] Rheumatoid factor is an antibody that is not usually present in the normal individual. However, most labs do not offer this test yet [1, 18]. All statistical analyses were conducted using R version 3.6.3. To investigate whether the anti-CCP antibody became negative over time, we obtained the latest anti-CCP antibody titer in January 2020 from the medical records of 64 anti-CCP-positive CTD patients whose anti-CCP antibody titers had been measured. 2023 BioMed Central Ltd unless otherwise stated. Patients with chronic inflammatory diseases are often treated with immunosuppressants and therefore are of particular concern during the SARS-CoV-2 pandemic. 1992;19(3):42430. 2003;48(10):27419. 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.". Your doctor may order an anti-dsDNA if you have a positive antinuclear antibody . 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%. Anti-citrullinated peptide (anti-CCP): antibodies against proteins with post-translational modification of arginine, which may have a role in pathogenesis of RA Newer generation of tests with similar sensitivity (80%) and improved specificity (95%) for RA compared to RF (should be ordered simultaneously in the appropriate clinical setting) 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. The immune system then produces antibodies to attack these . Description of the definition of the follow-up length. A negative result by itself does not rule out the disease. However, ACPA-positive healthy subjects, which account for 12% of the population [12, 13], do not have higher frequency of HLA-DRB1 SE [13]. Provided by the Springer Nature SharedIt content-sharing initiative. The Mann-Whitney U test was used to analyze absorbance difference between anti-CCP and anti-CAP patients. But ANCAs attack healthy cells known as neutrophils (a type of white blood cell) by mistake. Flow chart of the classification of patients with connective tissue disease (CTD). Clin Chem Lab Med. It affects about 0.6% of the US population with a global prevalence of 0.24%. 2014;66(12):181827. The test is ordered when a person displays signs and/or symptoms of rheumatoid arthritis. Eight hundred and forty-two CTD patients were selected from the CTD database in our division as of December 2012. J Rheumatol. Shiboski SC, Shiboski CH, Criswell L, Baer A, Challacombe S, Lanfranchi H, et al. 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? Association between SARSCoV2 and SLE is not clear. Information is shared for educational purposes only. Today, anti-histone antibodies are still used as a marker for systemic lupus . Most of the time, a positive test result for antinuclear antibodies (ANA) indicates the presence of an autoimmune disorder. Hedstrom AK, Ronnelid J, Klareskog L, Alfredsson L: Complex relationships of smoking, HLA-DRB1 genes, and serologic profiles in patients with early rheumatoid arthritis: Update from a Swedish population-based case-control study. (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.
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