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Medicine Mar 2019Rheumatoid arthritis (RA) is a chronic debilitating inflammatory disease affecting mainly the joint, surrounding tissue and other extra-articular structures in the body.... (Observational Study)
Observational Study
Rheumatoid arthritis (RA) is a chronic debilitating inflammatory disease affecting mainly the joint, surrounding tissue and other extra-articular structures in the body. RA can lead to destruction of bone and cartilage which may cause severe disability and it is characterized by the presence of serum rheumatoid factor (RF). The anti-cyclic citrullinate peptide (anti-CCP) antibody is another serum biomarker used in RA diagnosis with higher sensitivity and specificity.In this cross-sectional study with retrospective record review, 159 established RA patients from Hospital Universiti Sains Malaysia (HUSM) were recruited. Enzyme-linked immunosorbent assays (ELISAs) for serum RF and anti-CCP were performed. Our goal was to evaluate the significance of anti-CCP antibody in predicting the disease activity and progression in terms of radiological and extra-articular manifestations upon diagnosis.Of the 159 RA patients included in this study, mean age was 48.3 years old and majority (n = 134; 84.3%) were female. A total of 83 (52.2%) and 99 (62.3%) patients had anti-CCP antibody and RF, respectively. Mean Disease Activity Score-28 for Rheumatoid Arthritis with erythrocyte sedimentation rate (ESR) (DAS28-ESR) score for all patients was 4.74 (medium and high disease activity). Fifty-eight (36.5%) patients had radiological defects and 49 (30.8%) patients had extra-articular involvement manifested by rheumatoid nodule, pulmonary involvement, and anemia.In terms of anti-CCP antibody association with clinical and laboratory parameters, a significant co-occurrence of RF and anti-CCP antibody (P = .002) was observed. Anti-CCP antibody was significantly associated with radiological defects in which majority of patients with such defects (n = 40/58; 68.9%) were positive for anti-CCP antibody (P = .001). However, there was no significant difference between mean and classes of disease activity score and extra-articular manifestations between different anti-CCP antibody groups. In addition, extra-articular manifestations were not associated with high disease activity upon RA diagnosisThere was a significant association between anti-CCP antibody positivity and positive RF. Radiological defects were the sole clinical parameter significantly associated with anti-CCP antibody positivity, indicating that patients positive for anti-CCP antibody should be routinely monitored for radiological defects and their onset.
Topics: Adult; Age Factors; Age of Onset; Anti-Citrullinated Protein Antibodies; Arthritis, Rheumatoid; Biomarkers; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Malaysia; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; Rheumatoid Factor; Severity of Illness Index; Sex Factors
PubMed: 30896663
DOI: 10.1097/MD.0000000000014945 -
Annals of the Rheumatic Diseases Jun 1981Tests for antiperinuclear factor (APF) demonstrable by indirect immunofluorescence (IF) on smears of human buccal mucosal cells and for antibodies to keratin (AKA)...
Tests for antiperinuclear factor (APF) demonstrable by indirect immunofluorescence (IF) on smears of human buccal mucosal cells and for antibodies to keratin (AKA) detected on cryostat sections of rat oesophagus were performed on serum from 102 cases of rheumatoid arthritis (RA) and 117 controls. APF was detected in 92% of the cases of RA; positive tests obtained with non-RA sera were generally weaker than those given by the RA group, and the antibody in both RA and non-RA serum was predominantly IgG class. The difficulty in obtaining suitable substrate material previously reported was confirmed, and only 2 satisfactory donors were identified among 27 individuals tested. The incidence of keratin antibodies detected was found to be related to the site from which the tissue was taken; low oesophagus provided the best discrimination between RA and controls (51% and 5% positive respectively), and cardia of the stomach gave the highest incidence of staining in all groups. A laminar staining pattern was seen with most positive sera, but occasionally the keratinised layer was diffusely stained. The presence of AKA showed a marked correlation with both IgM rheumatoid factor and increased Clq binding in RA, but APF did not.
Topics: Antibodies; Antibodies, Antinuclear; Antigen-Antibody Complex; Arthritis, Rheumatoid; Female; Humans; Keratins; Male; Rheumatoid Factor
PubMed: 6166255
DOI: 10.1136/ard.40.3.263 -
Arthritis and Rheumatism May 2011
Topics: Arthritis, Rheumatoid; Biomarkers; Humans; Rheumatoid Factor
PubMed: 21538308
DOI: 10.1002/art.30197 -
Journal of Clinical Microbiology Jul 1985Immunoglobulin M (IgM) antibodies directed against IgG antibodies (rheumatoid factor [RF]) are known to occur often in patients with syphilis and to interfere with...
Immunoglobulin M (IgM) antibodies directed against IgG antibodies (rheumatoid factor [RF]) are known to occur often in patients with syphilis and to interfere with serological tests measuring specific antibodies of the IgM class. In this study we examined the occurrence and specificity of the RF and demonstrated a simple method to detect and eliminate the RF for a specific Treponema pallidum IgM enzyme-linked immunosorbent assay. We measured the occurrence of the RF with a sensitive enzyme-linked immunosorbent assay and found that it increased with the duration of syphilitic disease: 1 of 13 primary syphilis serum specimens, 3 of 13 secondary syphilis serum specimens, and 10 of 27 latent syphilis serum specimens were reactive in this RF test. Those sera containing IgM RF were immunoprecipitated with anti-human gamma chain antibodies and 2% polyethylene glycol until the RF was removed. One serum specimen from a patient in the secondary stage of syphilis and eight serum specimens from patients with latent disease still presented the RF after immunoprecipitation. Removal of the IgG antibodies also improved the sensitivity of the treponemal IgM test, indicating competition of these antibodies for binding sites of the antigen. The enzyme-linked immunosorbent assays for detection of RF and antitreponemal IgM antibodies are performed on the same plate. Theoretically, only sera positive for both tests have to be immunoprecipitated. But our findings indicated an increase in sensitivity of the IgM enzyme-linked immunosorbent assay after removal of IgG antibodies responsible for competition at the binding sites.
Topics: Antibodies, Anti-Idiotypic; Antibodies, Bacterial; Arthritis, Rheumatoid; Binding Sites, Antibody; Binding, Competitive; Enzyme-Linked Immunosorbent Assay; Humans; Immunoglobulin G; Immunoglobulin M; Latex Fixation Tests; Polyethylene Glycols; Rheumatoid Factor; Syphilis; Time Factors; Treponema pallidum
PubMed: 3894413
DOI: 10.1128/jcm.22.1.89-94.1985 -
Journal of the Royal Society of Medicine Jun 1983
Review
Topics: Arthritis; Humans; Rheumatoid Factor; Spondylitis, Ankylosing; Terminology as Topic
PubMed: 6345777
DOI: 10.1177/014107688307600601 -
The Journal of Clinical Investigation Jun 1963
Topics: Humans; Molecular Weight; Rheumatoid Factor
PubMed: 14020954
DOI: 10.1172/JCI104780 -
BMC Biotechnology Aug 2015Fluorescence-enhancing microarray on plasmonic gold film is an attractive alternative to traditional enzyme-linked immunosorbent assay (ELISA) for cytokine detection...
Cytokine detection and simultaneous assessment of rheumatoid factor interference in human serum and synovial fluid using high-sensitivity protein arrays on plasmonic gold chips.
BACKGROUND
Fluorescence-enhancing microarray on plasmonic gold film is an attractive alternative to traditional enzyme-linked immunosorbent assay (ELISA) for cytokine detection because of the increased sensitivity. The assay chemistry is similar to an ELISA sandwich assay, but owing to the gold substrate, cytokine measurements are 10 to 100 times more sensitive and can be multiplexed. Plasmonic protein microarrays are, as other immunoassays, affected by the presence of heterophilic antibodies and rheumatoid factor may lead to analytical errors with serious implications for patient care. Here, we present a plasmonic gold substrate protein microarray for high-sensitivity detection of cytokines with simultaneous assessment of rheumatoid factor interference on a single chip.
RESULTS
Paired serum and synovial fluid samples from patients with rheumatoid arthritis (n = 18), osteoarthritis (n = 9) or healthy controls (n = 10) were arrayed on near-infrared fluorescence enhancing plasmonic gold chips spotted with cytokine-specific capture antibody and isotype control antibody. Possible rheumatoid factor interference was visualised by a non-specific signal from the isotype control antibody, and pre-treatment of samples with heat-aggregated animal IgG eliminated this background contamination. The platform was optimised using the cytokine IL-20. The protein microarray platform allowed for the detection of human IL-20 at levels <1 pg/ml with reliable IL-20 quantification over a 5-log dynamic range. Samples for which rheumatoid factor caused artefacts were identified and a method for eliminating rheumatoid factor interference was developed and validated. IL-20 protein levels were significantly higher in synovial fluid samples from patients with rheumatoid arthritis compared to osteoarthritis (p < 0.001), while serum levels of IL-20 did not differ between patients with rheumatoid arthritis, osteoarthritis or healthy controls.
CONCLUSION
Using novel plasmonic gold chips, we developed a highly sensitive and accurate assay platform to detect lowly expressed cytokines in biological fluids, allowing for the elimination of rheumatoid factor interference in as little as 5 μl sample volume. The detection limit was below 1 pg/ml for IL-20 and linearity was achieved over a 5-log dynamic range. This technology is highly advantageous for cytokines where sensitivity or sample volume is critical or where assessment of rheumatoid factor interference needs addressed and eliminated.
Topics: Animals; Arthritis, Rheumatoid; Female; Gold; Humans; Immunoassay; Interleukins; Male; Osteoarthritis; Protein Array Analysis; Rheumatoid Factor; Synovial Fluid
PubMed: 26268325
DOI: 10.1186/s12896-015-0186-0 -
Arthritis Research & Therapy 2009In a previous issue of Arthritis Research and Therapy, Ursum and colleagues report the relative stabilities of anticitrullinated protein/peptide antibodies (ACPAs) and...
In a previous issue of Arthritis Research and Therapy, Ursum and colleagues report the relative stabilities of anticitrullinated protein/peptide antibodies (ACPAs) and IgM rheumatoid factors during the course of rheumatoid arthritis and their differential correlation with markers of the acute-phase response. These findings add to a growing body of evidence highlighting the distinct nature of these two autoantibody systems and the role of ACPAs as a disease-specific marker of rheumatoid arthritis.
Topics: Acute-Phase Reaction; Arthritis, Rheumatoid; Autoantibodies; Autoantigens; Biomarkers; Citrulline; Humans; Immunoglobulin M; Rheumatoid Factor
PubMed: 19796372
DOI: 10.1186/ar2786 -
The Journal of Rheumatology Aug 2010To validate in a general patient population (GPP) the clinical value of measuring rheumatoid factor (RF) isotypes in relationship to IgG anti-cyclic citrullinated...
OBJECTIVE
To validate in a general patient population (GPP) the clinical value of measuring rheumatoid factor (RF) isotypes in relationship to IgG anti-cyclic citrullinated peptide (CCP) antibodies (CCP2 and CCP3).
METHODS
Serum samples were obtained as follows: 1021 GPP, for whom RF was ordered for diagnosis, 137 with rheumatoid arthritis (RA), 100 healthy blood donors (HBD), and 50 with systemic lupus erythematosus. Turbidimetry and ELISA were utilized for RF screening, and individual RF isotypes and IgG anti-CCP antibodies were measured by ELISA; RF IgG was measured after pepsin digestion.
RESULTS
We validated the generally accepted 90%-98% positive predictive value (PPV) and about 68% sensitivity of the anti-CCP2 test on our diagnosed cohorts as 96% (95% CI 89-99) and 65% (95% CI 56-73), respectively. The 282 RF IgM+ specimens identified in the GPP were subdivided into 3 subsets: (1) 83 as RF IgM+ IgG+ IgA+ with 63% (95% CI 51-73) anti-CCP2+ (i.e., sensitivity similar to the RA cohort); (2) 50 as RF IgM+ IgG- IgA+ with significantly fewer anti-CCP2+ (22%; 95% CI 12-36); and (3) about half as IgM+ IgG- IgA- with just 3% (95% CI 1-8) anti-CCP2+, i.e., not significantly different from the 1% (95% CI 0-5) in HBD. Thus, the chance for a specimen in the GPP to be anti-CCP2+ (i.e., to come from an RA patient) was increased by 7- and 21-fold, respectively, by identifying RF IgA and IgG in addition to IgM. About one-third of anti-CCP- RA patients in our cohort were RF IgM+ IgG+ IgA+, reflected as 3.4% in the anti-CCP2- GPP. The agreement between anti-CCP2 and anti-CCP3 was significantly higher for RF+ RA and GPP patients, 86% (95% CI 78-93) and 83% (95% CI 73-91), respectively, than for the RF- RA (27%; 95% CI 6-61), RF- GPP (4%; 95% CI 0-19), and non-RA controls. Anti-CCP2 but not anti-CCP3 significantly distinguished the HBD from the GPP (95% CI).
CONCLUSION
Measurement of the 3 isotypes of RF may increase by 7- to 21-fold the chance of making the serologic diagnosis of RA; a testing algorithm is proposed. The anti-CCP antibody response appears significantly less peptide-specific in the presence of IgM RF than in its absence.
Topics: Adolescent; Adult; Aged; Arthritis, Rheumatoid; Female; Humans; Immunoglobulin G; Immunoglobulin Isotypes; Lupus Erythematosus, Systemic; Male; Middle Aged; Peptides, Cyclic; Predictive Value of Tests; Rheumatoid Factor; Serologic Tests; Young Adult
PubMed: 20516016
DOI: 10.3899/jrheum.091236 -
Medicine Jun 2019Rheumatoid Arthritis (RA) is a serious chronic disease which will result in serious syndrome such as joints stiffness, disability, and death. The major medications...
BACKGROUND
Rheumatoid Arthritis (RA) is a serious chronic disease which will result in serious syndrome such as joints stiffness, disability, and death. The major medications treating RA usually make sense and side effects, while moxibustion is known as a safe and effective treatment for RA. This review aims to systematically evaluate the effect and safety of moxibustion for treating RA.
METHODS
The following databases will be searched from their inception to March 2019: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Wan-Fang Databases, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Citation Information by National Institute of Informatics, Chinese Scientific Journal Database (VIP Database). Two reviewers will search these databases, select data and measure the quality of studies independently. The methodological quality will be assessed by the Cochrane risk of bias tool. Data will be synthesized by either the fixed-effects or random-effects model according to a heterogeneity test. The primary outcome is symptom evaluation including morning stiffness, pain and joint swelling. The number of joints affected by RA, adverse effects, quality of life, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and Rheumatoid factor (RF) will be evaluated as secondary outcomes. Risk ratio for dichotomous data and mean differences with a 95% confidence interval for continuous data will be adopted to express the effect and safety of acupuncture for RA.
RESULTS
This study will provide a high-quality synthesis of current evidence of moxibustion for asthma from several aspects including morning stiffness, pain and joint swelling. The number of joints affected by RA, adverse effects, quality of life, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and Rheumatoid factor (RF).
CONCLUSION
The conclusion of our study will provide updated evidence to judge whether moxibustion is an effective and safe intervention for patients with RA.
ETHICS AND DISSEMINATION
As individuals will not be involved, the ethical approval will not be required. This review will be published in a peer-reviewed journal or at a relevant conference.
PROSPERO REGISTRATION NUMBER
CRD42019126685.
Topics: Arthritis, Rheumatoid; Blood Sedimentation; C-Reactive Protein; Chronic Disease; Humans; Moxibustion; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic; Research Design; Rheumatoid Factor; Severity of Illness Index
PubMed: 31169700
DOI: 10.1097/MD.0000000000015899