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Diagnostic accuracy of the anti-citrulline antibody assay for rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is the most common autoimmune rheumatic disease, but specific and practicable tests for its diagnosis are lacking. We evaluated the diagnostic accuracy of a new commercial ELISA in detecting anti-cyclic citrullinated peptide (CCP) antibodies for the diagnosis of RA. METHODS: Anti-CCP antibodies were determined in 330 serum samples: 98 from RA patients and 232 from controls, including patients with connective tissue diseases, other rheumatic diseases, viral infections, Lyme disease, autoimmune thyroiditis, cancer, and monoclonal gammopathy, and sex- and age-matched healthy subjects. Intra- and interassay CVs were 5-13% and 9-17%, respectively. Rheumatoid factor (RF) was also assayed in every sample, and results were compared to anti-CCP for sensitivity and specificity. RESULTS: At a cutoff value of 50 units, sensitivity was 41% (confidence interval, 31-50%) and specificity was 97.8% (95-100%). Anti-CCP-positive RA patients had a mean antibody concentration of 1100 units (range, 57-3419 units), and anti-CCP-negative RA patients and controls had mean values of 7.6 and 6.8 units, respectively (range, 1-39 units). The area under the ROC curve was 0.71 (95% confidence interval, 0.63-0.78). RF had a higher sensitivity (62%) and a lower specificity (84%) than anti-CCP. When the two antibodies were used together, specificity was 99.6%. CONCLUSION: Anti-CCP antibody testing may be useful if performed concomitantly with RF assay to diagnose patients with suspected early RA.

Adult↗

[Autoantibodies in the diagnosis of rheumatoid arthritis. Utility of anti-cyclic citrullinated peptides].

Rheumatoid arthritis (RA) is one of the commonest inflammatory joint diseases, affecting about 1% of population. Despite its high prevalence, many aspects of its etiopathogeny remain unclarified. Recently, some important findings related to RA pathogenesis with a number of consequences on the treatment and prognosis of this aggressive disease have been reported. It is important to diagnose and to treat the disease early to avoid long-term damage. However, the search for a specific and sensitive serological test to early identify RA patients has yielded poor results. Autoantibodies are found in the sera of RA patients with a variable prevalence and have been classified into RA-specific and RA-unspecific antibodies. It has been recently demonstrated that many of those RA-specific autoantibodies recognize peptides that contain citrulline residues and, thus, a new test to measure the presence of anti-cyclic citrullinated peptides (CCP) antibodies has been developed. Research publications about the utility of anti-CCP antibodies not only in the diagnosis, but also in the prognosis, of RA are increasing exponentially. In fact, the value of the measurement of anti-CCP antibodies is already widely recognized. This review summarizes the most important data about the autoantibodies employed to date in the diagnosis of RA, including anti-CCP antibodies.

Algorithms↗

Anti-cyclic citrullinated peptide antibodies, IgM and IgA rheumatoid factors in the diagnosis and prognosis of rheumatoid arthritis.

OBJECTIVES: To evaluate the association of anti-cyclic citrullinated peptide (anti-CCP) antibodies with immunoglobulin (Ig) M and IgA rheumatoid factors (RF) in discriminating between rheumatoid arthritis (RA) and other rheumatic diseases, and to determine, in a longitudinal study, whether clinical signs of disease severity are associated with the presence of these autoantibodies at the time of patient inclusion. METHODS: The presence of these three markers was determined in 196 patients with established RA, 239 non-RA controls with various rheumatic diseases (cross-sectional study) and in 27 patients with arthritis of less than 1 yr disease duration who were subsequently followed during about 8 yr (longitudinal study). At the time of follow-up, 21 of these 27 patients had RA. They were further evaluated and several clinical variables were recorded. RESULTS: The specificity was significantly increased (from 82-90% to 98% in the cross-sectional study) when the combination of anti-CCP antibodies with IgA RF or the combination of the three serological markers was used. An association was observed between the presence of the three autoantibodies and clinical signs of disease severity (functional disability, presence of erosions and absence of clinical remission). CONCLUSIONS: The presence either of anti-CCP antibodies and IgA RF or of the three markers appears to be useful in the diagnosis of RA. Their association with clinical signs of disease severity at the time of patient inclusion suggests their potential usefulness as markers for prognosis.

Adult↗

Investigation of polymorphisms in the PADI4 gene in determining severity of inflammatory polyarthritis.

BACKGROUND: A functional haplotype of the peptidylarginine deiminase 4 (PADI4) gene has recently been identified as a rheumatoid arthritis susceptibility gene in a Japanese but not in a UK population. One possible explanation for this disparity is that the gene determines severity of rather than susceptibility to inflammatory polyarthritis (IP) and that the UK and Japanese cohorts differed in terms of outcome. AIM: To examine the association between individual PADI4 single nucleotide polymorphisms (SNPs) and haplotypes, with the development and severity of erosions by five years in patients with IP. METHODS: 438 patients from the NOAR inception cohort of patients with IP were x rayed five years after presentation with early IP. Association with four exonic SNPs (padi4_89*G/A, padi4_90*T/C, padi4_92*G/C, and padi4_104*T/C), mapping to the PADI4 gene and defining a haplotype previously reported to be associated with rheumatoid arthritis, was investigated. Patients were compared for the presence, extent, and progression of erosions by five years and the presence of antibodies to citrullinated peptide (anti-CCP antibodies). RESULTS: There was no association between individual PADI4 SNPs or haplotypes and the development or extent of erosions by five years. Restricting analysis to patients who satisfied ACR criteria for rheumatoid arthritis by five years did not alter the conclusions. No association with presence of anti-CCP antibodies was detected. CONCLUSIONS: No evidence was found for association of the PADI4 gene with severity as assessed by erosive outcome at five years or with presence of anti-CCP antibodies in patients with IP.

Adult↗

Citrullinated proteins: sparks that may ignite the fire in rheumatoid arthritis.

Antibodies directed to citrullinated proteins (e.g. anti-CCP [cyclic citrullinated peptide] antibodies) are highly specific for rheumatoid arthritis (RA). These antibodies are produced at the site of inflammation in RA, and therefore citrullinated antigens are also expected to be present in the inflamed synovium. We discuss literature showing that the presence of citrullinated proteins in the synovium is not specific for RA. The RA-specific antibodies are therefore most likely the result of an abnormal immune response that specifically occurs in RA patients. It was recently shown that presence of anti-CCP antibodies precedes the onset of clinical symptoms of RA by years. It thus appears that it may take years for initial events that cause the generation of anti-CCP antibodies to develop into full-blown disease.

Animals↗

[Anti-cyclic citrullinated peptide antibodies as a diagnostic test for rheumatoid arthritis].

Early diagnosis of rheumatoid arthritis (RA) is important since aggressive therapy should begin at an early stage. Diagnosis is made on a clinical basis, supported by the determination of rheumatoid factor (RF). However, RF is also positive in healthy subjects, as well as in other autoimmune and infectious diseases. Two other diagnostic markers with a high specificity for RA, antiperinuclear factor (APF) and antikeratin antibodies (AKA), are not in general use because of technical difficulties. APF and AKA are antifilaggrin antibodies (AFA) that bind to determinants rich in the unusual amino acid citrulline, generated by posttranscriptional modification of arginine residues by the enzyme peptidylarginine deiminase (PAD). Enzymatic determination of recombinant filaggrin fragments produces linear peptides, which are recognized by RA-specific autoantibodies. After substitution of serine by cysteine, a cyclic peptide is formed. The conformational change mimics the original structure of the filaggrin and enhances the affinity of the antibodies. Recently, an anti-cyclic citrullinated peptide (anti-CCP) ELISA was developed. The sensitivity of this test is usually 51%-68%, with a specificity of about 96%-98% (significantly higher than that of RF). Together with RF, anti-CCP increases the ability to diagnose patients with early RA. The test might help to predict which patients will develop persistent disease with evidence of radiologic lesions. Implementation of the highly specific anti-CCP test in conjunction with RF would enable reliable early diagnosis in some cases and allow the initiation of aggressive therapy with disease modifying anti-rheumatic drugs (DMARDs).

Antibodies↗

Anti-cyclic citrullinated antibodies: complementary to IgM rheumatoid factor in the early diagnosis of rheumatoid arthritis.

AIMS: To compare the diagnostic sensitivity of anti-cyclic citrullinated (CCP) antibodies and rheumatoid factor (RF) in rheumatoid arthritis (RA) within a general hospital setting. METHOD: Using the American College of Rheumatology (ACR) classification criteria as a gold standard, the frequency of RF and anti-CCP antibody positivity was compared between two groups of RA patients: those with disease duration less than 2 years (early RA, ERA) and those with disease duration more than 2 years (late RA, LRA). RESULTS: In ERA, the diagnostic sensitivity of RF and anti-CCP antibodies was 57% and 79% respectively. In LRA, it was 81% and 84% respectively. CONCLUSION: Anti-CCP antibodies are 20% more sensitivity than RF in the diagnosis of early RA.

Arthritis, Rheumatoid↗

Quantifying and improving rheumatoid arthritis algorithm performance in biobank settings.

OBJECTIVE: To quantify and improve the performance of standard rheumatoid arthritis (RA) algorithms in a biobank setting. METHODS: This retrospective cohort study within the Mayo Clinic (MC) Biobank and MC Tapestry Study identified RA cases by presence of at least two RA codes OR positive anti-cyclic citrullinated peptide antibodies (CCP) plus disease-modifying anti-rheumatic drug (DMARD) prescription as of 7/18/2022. Rheumatology physicians manually verified all RA cases using RA criteria and/or rheumatology physician diagnosis plus DMARD use. All other biobank participants served as non-RA controls. We defined seropositivity as rheumatoid factor and/or anti-CCP positivity. We assessed rules-based and Electronic Medical Records and Genomics (eMERGE) RA algorithms using positive predictive value (PPV). Finally, we developed a novel RA algorithm using a LASSO-based machine learning approach with five-fold cross validation. RESULTS: We identified 1,316 confirmed RA cases (968 MC Biobank, 348 Tapestry, 70 % seropositive) and 82,123 non-RA controls (mean age 65, 61 % female). The PPV of 3 RA codes was 43 %, codes plus DMARD was 54 %, and codes plus DMARD plus seropositivity was 85 %. The PPV of eMERGE was 77 %. Available in the MC Biobank, self-reported RA (PPV 10 %) only minimally improved algorithm performance (PPV from 83 % to 85 %), whereas family history of RA (PPV 3 %) worsened performance. At 90 % PPV, the novel RA algorithm incorporating key variables such as anti-CCP and DMARD use increased sensitivity by 4-11 % compared to eMERGE. CONCLUSION: Rules-based and eMERGE RA algorithms had worse performance in biobank than administrative settings. Our novel RA algorithm outperformed these standard algorithms.

Humans↗

Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis.

OBJECTIVE: To explore the changes in serologic variables and clinical disease activity following B lymphocyte depletion in 22 patients with rheumatoid arthritis (RA). METHODS: B lymphocyte depletion was attained using combination therapy based on the monoclonal anti-CD20 antibody rituximab. Levels of a serologic indicator of inflammation, C-reactive protein (CRP), of antimicrobial antibodies, of autoantibodies including IgA-, IgM-, and IgG-class rheumatoid factors (RF), and of antibodies to cyclic citrullinated peptide (anti-CCP) were assayed. RESULTS: The majority of patients showed a marked clinical improvement after treatment with rituximab, with benefit lasting up to 33 months. Levels of total serum immunoglobulins fell, although the mean values each remained within the normal range. Whereas the IgM-RF response paralleled the changes in total serum IgM levels, the levels of IgA-RF, IgG-RF, and IgG and anti-CCP antibodies decreased significantly more than did those of their corresponding total serum immunoglobulin classes. The kinetics for the reduction in CRP levels also paralleled the decreases in autoantibody levels. In contrast, levels of antimicrobial antibodies did not change significantly. B lymphocyte return occurred up to 21 months posttreatment. The time to relapse after B lymphocyte return was often long and unpredictable (range 0-17 months). Relapse was, however, closely correlated with rises in the level of at least one autoantibody. Increased autoantibody levels were rarely observed in the absence of clinical change. CONCLUSION: Following B lymphocyte depletion in patients with RA, a positive clinical response occurred in correlation with a significant drop in the levels of CRP and autoantibodies. Antibacterial antibody levels were relatively well maintained. B lymphocyte return preceded relapse in all patients. There was also a temporal relationship between clinical relapse and rises in autoantibody levels. Although these observations are consistent with a role for B lymphocytes in the pathogenesis of RA, the precise mechanisms involved remain unclear.

Adult↗

Citrullination of synovial proteins in murine models of rheumatoid arthritis.

OBJECTIVE: Antibodies directed to citrulline-containing proteins are highly specific for rheumatoid arthritis (RA) and can be detected in up to 80% of patients with RA. Citrulline is a nonstandard amino acid that can be incorporated into proteins only by posttranslational modification of arginine by peptidylarginine deiminase (PAD) enzymes. The objective of this study was to investigate the presence of anticitrulline antibodies, PAD enzymes, and citrullinated antigens in mouse models of both acute and chronic destructive arthritis: streptococcal cell wall (SCW)-induced arthritis and collagen-induced arthritis (CIA), respectively. METHODS: Synovial tissue biopsy specimens were obtained from naive mice, mice with CIA, and mice with SCW-induced arthritis. The expression of messenger RNA (mRNA) for PAD enzymes was analyzed by reverse transcriptase-polymerase chain reaction; the presence of PAD proteins and their products (citrullinated proteins) was analyzed by Western blotting and by immunolocalization. The presence of anticitrullinated protein antibodies was investigated by an anti-cyclic citrullinated peptide (anti-CCP) enzyme-linked immunosorbent assay (ELISA) and an ELISA using in vitro citrullinated fibrinogen. RESULTS: In both mouse models, PAD type 2 (PAD2) mRNA was present in the synovium but was not translated into PAD2 protein. In contrast, PAD4 mRNA, although absent from healthy synovium, was readily transcribed and translated by polymorphonuclear neutrophils infiltrating the synovial tissue during inflammation. As a consequence, several synovial proteins were subjected to citrullination. One of these proteins was identified as fibrin, which has been reported to be citrullinated also in synovium of patients with RA. Although generation of citrullinated antigens during synovial inflammation in the mice was eminent, no anti-CCP antibodies could be detected. CONCLUSION: Citrullination of synovial antigens is an active process during joint inflammation in both mice and humans, but the induction of autoantibodies directed to these proteins is a more specific phenomenon, detectable only in human RA patients.

Animals↗

Endogenous Retroelement Activation is Implicated in Interferon-α Production and Anti-Cyclic Citrullinated Peptide Autoantibody Generation in Early Rheumatoid Arthritis.

OBJECTIVE: Endogenous retroelements (EREs) stimulate type 1 interferon (IFN-I) production but have not been explored as potential interferonogenic triggers in rheumatoid arthritis (RA). We investigated ERE expression in early RA (eRA), a period in which IFN-I levels are increased. METHODS: ERE expression (long terminal repeat [LTR] 5, long interspersed nuclear element 1 [LINE-1], and short interspersed nuclear element [SINE]) in disease-modifying treatment-na&#xef;ve eRA whole-blood and bulk synovial tissue samples was examined by reverse transcription-polymerase chain reaction and NanoString alongside IFN-&#x3b1; activity. Circulating lymphocyte subsets, including B cell subsets, from patients with eRA and early psoriatic arthritis (ePsA) were flow cytometrically sorted and similarly examined. Existing established RA and osteoarthritis (OA) synovial single-cell sequencing data were reinterrogated to identify repeat elements, and associations were explored. RESULTS: There was significant coexpression of all ERE classes and IFNA in eRA synovial tissue samples (n = 22, P < 0.0001) and significant positive associations between whole-blood LINE-1 expression (n = 56) and circulating IFN-&#x3b1; protein (P = 0.018) and anti-cyclic citrullinated peptide (anti-CCP) titers (P < 0.0001). ERE expression was highest in circulating eRA B cells, particularly na&#xef;ve B cells compared with ePsA, with possible ERE regulation by SAM and HD Domain Containing Deoxynucleoside Triphosphate Triphosphohydrolase 1 transcription (SAMDH1) implicated and associations with IFNA again observed. Finally, in established RA synovium, LTRs, particularly human endogenous retroviral sequence K (HERVK), were most increased in RA compared with OA, in which, for all synovial subsets (monocytes, B cells, T cells, and fibroblasts), ERE expression associated with increased IFN-I signaling (P < 0.001). CONCLUSION: Peripheral blood and synovial ERE expression is examined for the first time in eRA, highlighting both a potential causal relationship between ERE and IFN-I production and an intriguing association with anti-CCP autoantibodies. This suggests EREs may contribute to RA pathophysiology with implications for future novel therapeutic strategies.

Humans↗

[Value of anti-cyclic citrullinated peptides antibodies in comparison with rheumatoid factor for rheumatoid arthritis diagnosis].

The detection of anti-cyclic citrullinated peptides (CCP) antibodies is a new marker for diagnosis of rheumatoid arthritis. We screened 100 patients suffering from rheumatic pathologies or from other affections where rheumatoid factor is frequently detected. The screening was assessed by a second generation ELISA (Immunoscan RA) in comparison with agglutination assay (Latex and Waaler-Rose) and specific ELISA (IgM, IgG and IgA). The sensitivity of the anti-CCP is good (>70%) with an excellent specificity (98%). In our study the predictive value of the Immunoscan RA reached 71% and more among patients with joints symptoms. Anti-CCP antibody test could serve as a better diagnosis marker than rheumatoid factor.

Agglutination Tests↗

Autoantibody profile in rheumatoid arthritis during long-term infliximab treatment.

The aim of the present study was to investigate the effect of long-term infliximab treatment on various autoantibodies in patients with rheumatoid arthritis. Serum samples from 30 consecutive patients, who were prospectively followed during infliximab and methotrexate therapy for refractory rheumatoid arthritis, were tested at baseline and after 30, 54 and 78 weeks. At these points, median values of the Disease Activity Score were 6.38 (interquartile range 5.30-6.75), 3.69 (2.67-4.62), 2.9 (2.39-4.65) and 3.71 (2.62-5.06), respectively. Various autoantibodies were assessed by standard indirect immunofluorescence and/or ELISA. Initially, 50% of patients were positive for antinuclear antibodies, and this figure increased to 80% after 78 weeks (P = 0.029). A less marked, similar increase was found for IgG and IgM anticardiolipin antibody titre, whereas the frequency of anti-double-stranded DNA antibodies (by ELISA) exhibited a transient rise (up to 16.7%) at 54 weeks and dropped to 0% at 78 weeks. Antibodies to proteinase-3 and myeloperoxidase were not detected. The proportion of patients who were positive for rheumatoid factor (RF) was similar at baseline and at 78 weeks (87% and 80%, respectively). However, the median RF titre exhibited a progressive reduction from 128 IU/ml (interquartile range 47-290 IU/ml) to 53 IU/ml (18-106 IU/ml). Anti-cyclic citrullinated peptide (CCP) antibodies were found in 83% of patients before therapy; anti-CCP antibody titre significantly decreased at 30 weeks but returned to baseline thereafter. In conclusion, the presence of anti-double-stranded DNA antibodies is a transient phenomenon, despite a stable increase in antinuclear and anticardiolipin antibodies. Also, the evolution of RF titres and that of anti-CCP antibody titres differed during long-term infliximab therapy.

Antibodies, Anticardiolipin↗

Serologic markers of early rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects symmetrically multiple joints. Recent therapeutic strategy has been focusing on the symptoms of the disease and the ways to prevent its progression as early as possible. Thus, early diagnosis is crucial since early therapy with disease-modifying anti-rheumatic drugs reduces the severity of joint damage. It is the early period of the development of the disease that a specific and sensitive serologic test is needed. The RA patient sera contains a lot of antibodies. Some of them are not specific for RA occurring also in other diseases, others are highly specific and detectable only in rheumatoid arthritis. Rheumatoid factor (RF) is a very sensitive but poorly specific marker which makes it rather an unsuitable antibody for rheumatoid arthritis. RA-specific antibodies can be very useful for early diagnosis and prognosis of the disease. Among the antibodies described in recent years the most promising candidates are the autoantibodies to antigens containing one or more than one citrulline residues (cyclic citrulline peptides, CCP) - the anti-CCP antibodies. They have been shown in recent research to play an important role in the diagnosis, prognosis and therapeutic approach to patients with RA. Their high specificity, the ability to diagnose RA early in its development and distinguish it from other nonerosive type of arthritis, make the anti-CCP a key serologic marker in the future.

Arthritis, Rheumatoid↗

The prevalence of autoantibodies against cartilage intermediate layer protein, YKL-39, osteopontin, and cyclic citrullinated peptide in patients with early-stage knee osteoarthritis: evidence of a variety of autoimmune processes.

We studied arthritis-related autoantibodies in 136 patients with knee osteoarthritis (OA) and 67 age- and sex-matched healthy individuals in the Shanghai District of China. Serum antibody titers for recombinant fusion proteins of cartilage intermediate layer protein (CILP) and YKL-39 were analyzed using enzyme-linked immunosorbent assay (ELISA) and Western blot. Serum antibody titers against recombinant osteopontin (OPN) and cyclic citrullinated peptide (CCP) antibodies were measured also using ELISA. Anti-CILP antibodies were detected in 25/136 OA patients but only 1/67 controls. Anti-YKL-39, anti-OPN, and anti-CCP antibodies were detected in 9/136, 11/136, and 7/136 of the OA patients, respectively, and 0/67 controls. There was rarely overlap of these antibodies in a single patient, suggesting distinct antigen specificity in each case. The antibodies were detected in patients with OA of grades II and III but not grade IV. The prevalence of autoantibodies to various arthritis-related proteins in early-stage knee OA supports the involvement of a specific immune response in initial cartilage degeneration in OA.

Adipokines↗

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.

Antibodies, Antineutrophil Cytoplasmic↗

Attitudes to early rheumatoid arthritis: changing patterns. Results of a survey.

OBJECTIVE: To determine if rheumatologists have changed their views on diagnosis and treatment of early rheumatoid arthritis (RA). METHODS: Three consecutive questionnaires were sent out to international rheumatologists in 1997, 2000, and 2003. The following aspects of early RA were covered: definition; patient referral time; diagnostic means; follow up intervals; and treatment strategies. All initial participants who responded to at least one of the follow up surveys were included in the analysis. RESULTS: RA is now defined by a smaller number of affected joints (monarthritis: 9.8% respondents in 1997 v 17.4% in 2003), and shorter symptom duration (<3 months: 65.5% in 1997 v 85.8% in 2003). Early referrals (<6 weeks) increased (8.9% in 1997 v 17.4% in 2003). Serological test for diagnosis was mostly rheumatoid factor (100% in 2003), but anti-CCP was already used by 17.4% in 2003. Follow up of patients with early RA intensified (every 2 weeks: 16.1% in 1997 v 30.4% in 2003; every month: 47.8% in 2003 v 64.3% in 1997). Treatment with disease modifying antirheumatic drugs (DMARDs) mainly comprised methotrexate, sulfasalazine, and antimalarial drugs. Leflunomide was among the two favourite DMARDs of 10.9% in 2003, whereas no biological agent was so. In 2003, 46.7% respondents started treatment with DMARDs if RA was suspected (30.9% in 1997); no one waited for erosions to occur (7.3% in 1997). CONCLUSION: The data obtained in this study suggest that the concept of diagnosing and treating RA early is accepted by a large proportion of the rheumatological community.

Antirheumatic Agents↗

Filaggrin related antibodies among the aged.

BACKGROUND: The mean age at onset of new cases of rheumatoid arthritis (RA) has increased markedly. Because the prevalence of false positive rheumatoid factor reactions increases with advancing age, the diagnostic value of this test has limitations among the aged. OBJECTIVE: To study the occurrence of two filaggrin related antibodies in an aged population. METHODS: The study covered 300 subjects aged 78-88 years, one of whom had RA. The sera were tested with enzyme linked immunosorbent assays (ELISAs), using filaggrin purified from human skin and citrullinated cyclic peptide (CCP) as antigens. RESULTS: One patient with RA was positive for both antibodies. When the cut off level for positive reactions was set at the 98th centile of healthy blood donors, 24 (8%) of the other subjects were positive for antibodies against filaggrin, but only one against CCP. CONCLUSION: The test for anti-CCP antibody has better specificity than the test for antibodies against filaggrin among the aged.

Aged↗