OBJECTIVETo study the objective diagnostic mechanisms on Chinese medical (CM) syndrome patterns of rheumatoid arthritis (RA), and to research different titers of rheumatoid factor (RF)/citrullinated protein antibody (CCP) in CM syndrome patterns of RA.

METHODSTotally 230 early RA patients were assigned to five CM syndrome pattern groups, i.e., the dampness-heat blockage group (50 cases), the cold-dampness blockage group (50 cases), the Shen-qi deficiency-cold group (50 cases), the Gan-Shen yin deficiency group (40 cases), and the blood stasis blockage group (40 cases). Another 100 healthy subjects were recruited as the healthy control group. RF-IGM, RF-IGA, RF-IGG, and anti-CCP antibody were detected and compared.

RESULTSThe titers of RF-IGM, RF-IGA, RF-IGG, and anti-CCP antibody were higher in all groups than in the healthy control groups (P < 0.01). As for the 5 groups, RF-IGM, RF-IGA,RF-IGG, and anti-CCP antibody were higher in the RA active stage than in the nonactive stage. They were higher in the dampness-heat blockage group in the RA active stage than in the Shen-qi deficiency-cold group, the Gan-shen yin deficiency group, and the blood stasis blockage group.

CONCLUSIONTiters of RF-IGM, RF-IGA, RF-IGG, and anti-CCP antibody could be taken as judging indicators for differentiating objective lab indices of CM syndromes and assessing the active stage of RA.

Adult ; Aged ; Arthritis, Rheumatoid ; blood ; diagnosis ; immunology ; Autoantibodies ; blood ; Case-Control Studies ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Peptides, Cyclic ; immunology ; Rheumatoid Factor ; immunology

OBJECTIVETo study the correlation between the expression of Fcgamma receptor II b (FcgammaRII b) on B cells and rheumatoid arthritis (RA) patients of Shen deficiency syndrome (SDS).

METHODSThere were 43 RA patients, including 26 of SDS and 17 of non-SDS. The expression levels of FcgammaRII b on naive B cells, memory B cells, and plasma blasts in the peripheral blood were detected by flow cytometry. The numbers of tender joints, numbers of swollen joints, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and disease activity score (DAS28), the correlation between the distribution of B cells and the expression level of FcgammaRII b in RA patients were analyzed. Besides, another 21 healthy volunteers were recruited as the control group.

RESULTSThe expression level of FcgammaRII b was 49.65% +/- 15.86% on memory B cells and 43.69% +/- 22.57% on plasma blasts in RA patients of SDS, significantly down-regulated when compared with those of the control group (64.03% +/- 6.01%, 66.59% +/- 10.18%, P < 0.01). The expression level of FcgammaRII b on memory B cells of RA patients of non-SDS was down-regulated more obviously when compared with that of the control group (52.70% +/- 9.52% versus 64.03% +/- 6.01%, P < 0.01). The expression level of FcgammaRII b on plasma blasts was obviously lower in RA patients of SDS than in RA patients of non-SDS (56.10% +/- 17.05%, P < 0.05). The expression level of FcgammaRII b on memory B cells was not correlated with numbers of tender joints, numbers of swollen joints, ESR, RF, or DAS28.

CONCLUSIONSThe defective immunological tolerance of B cells in RA patients of SDS might be closely correlated with down-regulation of FcgammaRII b on memory B cells and plasma blasts. There might exist genetic abnormality of FcgammaRII b gene in RA patients of SDS, thus inducing loss of autoimmunity tolerance.

Adult ; Arthritis, Rheumatoid ; blood ; diagnosis ; immunology ; B-Lymphocytes ; immunology ; metabolism ; Case-Control Studies ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Receptors, IgG ; immunology ; metabolism

OBJECTIVETo systematically evaluate the values of 4 serum markers in the diagnosis of rheumatoid arthritis (RA).

METHODSSerum samples were obtained from 278 RA patients and 510 control subjects and the levels of rheumatoid factor (RF), anticyclic citrullinated peptide antibody (CCP), antikeratin antibody (AKA), and glucose-6-phosphate isomerase (GPI) were detected using immune turbidimetry, ELISA, indirect immunofluorescence, and ELISA, respectively. The values of these 4 serum markers and their combinations in RA diagnosis were systemically assessed.

RESULTSIn RA diagnosis using one serum marker, two markers, and three or four markers, RF, RF+CCP, RF+CCP+GPI, respectively, had the highest sensitivity; CCP, CCP+AKA, and RF+CCP+AKA+GPI, respectively, had the highest specificity; CCP, CCP+GPI, and RF+CCP+AKA+GPI, respectively, had the highest positive predictive value; GPI, RF+CCP, and RF+CCP+GPI, respectively, had the highest negative predictive value; CCP, CCP+GPI, and RF+CCP+AKA+GPI, respectively, had the highest positive likely ratio; GPI, RF+CCP, and RF+CCP+GPI, respectively, had the lowest negative likely ratio.

CONCLUSIONCCP, RF+CCP, and RF+CCP+GPI are the most ideal for RA diagnosis using one, two, and three or more markers, respectively. CCP is the essential marker for RA diagnosis, and a combined detection of the serum makers can significantly improve the diagnostic accuracy.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Arthritis, Rheumatoid ; blood ; diagnosis ; Autoantibodies ; blood ; Biomarkers ; blood ; Case-Control Studies ; Citrulline ; immunology ; Female ; Glucose-6-Phosphate Isomerase ; blood ; Humans ; Keratins ; immunology ; Male ; Middle Aged ; Rheumatoid Factor ; blood ; Young Adult

OBJECTIVETo explore the diagnostic value of serum anti-cyclic citrullinated peptide (Anti-CCP) antibodies in patients with rheumatoid arthritis (RA).

METHODSAnti-CCP antibodies were detected in the serum samples of 120 RA patients, 71 non-RA patients with various rheumatic diseases, and 50 normal controls by enzyme-linked immunosorbent assay (ELISA) using domestic and imported commercial detection kits. Rheumatoid factors (RF) were assayed by immune-nephelometry. The correlation between Anti-CCP and RF in RA diagnosis was analyzed by calculating the area under curve of the receiver operating characteristic (ROC) curve.

RESULTSThe positive rates for Anti-CCP, detected using both domestic and imported kits, were 61.7% (74/120) and 69.2% (83/120) in RA group, significantly higher than those in the non-RA group (9.9%, 7/71 and 7.0%, 5/71) and normal control group (both 0, P<0.001). The sensitivities for Anti-CCP and RF were 69.2% and 64.2%, and the specificities were 92.9% and 67.6%, respectively. The positive predictive value was 94.3% for Anti-CCP and 77.0% for RF, whereas the negative predictive value was 64.1% for Anti-CCP and 52.7% for RF. The likelihood ratio (LR) was 9.82 for anti-CCP and 1.98 for RF. The area under curve of ROC for Anti-CCP was 0.829 and 0.740 for RF. Anti-CCP antibodies had greater diagnostic value than RF in RA diagnosis, and Anti-CCP showed significant correlation with RF (r=0.29, P=0.001).

CONCLUSIONAnti-CCP antibodies are an excellent serological marker for RA, which shows high diagnostic specificity at early stage, and can increase its diagnostic value when combined with RF detection, but the role of Anti-CCP in the occurrence and prognosis of RA remains to be further investigated.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies ; blood ; immunology ; Arthritis, Rheumatoid ; blood ; diagnosis ; Child ; Female ; Humans ; Male ; Middle Aged ; Peptides, Cyclic ; immunology ; ROC Curve ; Rheumatoid Factor ; blood ; Young Adult

BACKGROUND: Inflammatory cytokines such as tumor necrosis factor alpha (TNFalpha) and interleukin (IL)-6 play an important role in pathophysiology of rheumatoid arthritis (RA). We investigated the possibility whether TNFalpha and IL-6 could be used as an objective marker reflecting treatment response in RA. METHODS: Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and rheumatoid factor (RF) together with TNFalpha and IL-6 were measured in 159 specimens obtained from 95 RA patients. RA patients were divided into pre-treatment, methotrexate (MTX) and non-MTX groups by treatment regimen and into inactive and active groups by disease activity. The agreement between changes in marker levels and treatment response, and the correlation between each marker were analyzed. RESULTS: IL-6 was higher in active than in inactive group of patients in all three different treatment subgroups, but TNFalpha was not different between the two groups. IL-6 showed a better agreement with treatment response (MTX group, K=0.58; non-MTX group, K=0.21) than ESR or CRP, whereas TNFalpha did not show an agreement with treatment response. IL-6 was correlated with both ESR (r=0.22) and CRP (r=0.54), but TNFalpha was correlated only with ESR (r=0.21). CONCLUSIONS: Unlike TNFalpha, IL-6 reflects disease activity of RA and shows a better agreement with treatment response than ESR or CRP, indicating that it has an association with clinical features of RA. Therefore IL-6 could be used as an additional marker in the evaluation of treatment response when markers like ESR or CRP show results discordant from clinical features.
Adult ; Arthritis, Rheumatoid/diagnosis/*drug therapy/immunology ; Biological Markers/blood ; Blood Sedimentation ; C-Reactive Protein/analysis ; Female ; Humans ; Interleukin-6/*blood ; Methotrexate/therapeutic use ; Middle Aged ; Rheumatoid Factor/blood ; Tumor Necrosis Factor-alpha/*blood

BACKGROUND: Despite its unsatisfactory specificity, rheumatoid factor (RF) is the only serologic marker included in the diagnostic criteria of the American College of Rheumatology (ACR) for rheumatoid arthritis. Recently, the diagnostic value of anti-cyclic citrullinated peptide (CCP) antibodies has been emphasized in rheumatoid arthritis (RA) due to its high specificity. To evaluate the second generation of anti-CCP antibodies as a diagnostic marker, we evaluated anti-CCP test in 163 individuals. METHODS: The study population was divided into the following four groups: RA group (n=18), other disease group with arthritic symptoms (n=44), other disease group without arthritic symptoms (n=45), and healthy group (n=56). Anti-CCP was measured by an ELISA analyzer (Coda, Bio-Rad, USA) with Immunoscan RA (Euro-Diagnostica, Malmo, Sweden) and RF was measured by an automated chemistry analyzer (Toshiba, Japan) with RF-LATEX X1 (Denka Seiken, Japan). RESULTS: The sensitivity of anti-CCP and RF was 72.2% and 100%, respectively, and the respective figures for the specificity were 96.6% and 73%. On each ROC curve, the area under the curve was 0.867 for anti-CCP and 0.959 for RF. In other disease groups, most of the false positive cases of RF were found in the patients with hyperlipidemia or HBV carriage. However, anti-CCP was not detected in any of the patients with these two conditions. False positive rates of RF in the three control groups were 34.1% in other disease group with arthritic symptoms, 48.9% in the other disease group without arthritic symptoms, and 3.6% in healthy group. The respective figures for anti-CCP were 6.8%, 2.2%, and 1.8%. CONCLUSIONS: The specificity of anti-CCP antibodies was higher than that of RF for discriminating RA from other diseases, especially in the patients with hyperlipidemia or HBV carriage. With its high specificity, anti-CCP antibodies can play an additive role in establishing the diagnosis of RA in patients with RF positivity.
Adult ; Arthritis, Rheumatoid/*diagnosis ; Autoantibodies/*blood ; Biological Markers/blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Middle Aged ; Peptides, Cyclic/*immunology ; ROC Curve ; Reagent Kits, Diagnostic ; Rheumatoid Factor/blood ; Sensitivity and Specificity

Filaggrin is expressed in the cornified layer of epidermis and known to be one of the antigenic targets in rheumatoid arthritis. Although the citrulline residue in filaggrin is thought to be an antigenic determinant recognized by autoantibodies, the diagnostic sensitivity of synthetic citrullinated peptide is variable. To investigate the implication of anti-filaggrin antibodies recognizing uncitrullinated filaggrin in rheumatoid arthritis, we assayed antibody titers using unmodified recombinant filaggrin in the sera from 73 patients with rheumatoid arthritis, 150 patients with other connective tissue diseases and 70 normal controls. We also performed the correlation analysis between antibody titers and the clinical variables in patients with rheumatoid arthritis. Titers of IgG anti-filaggrin antibodies were significantly higher in rheumatoid arthritis patients compared to normal controls (P=0.02), but not in patients with osteoarthritis, ankylosing spondylitis or systemic lupus erythematosus. IgG anti-filaggrin antibodies were more frequently found in patients with rheumatoid arthritis compared to normal controls (12.3% vs 1.4% respectively, P=0.04). An anti-filaggrin antibody titer was correlated with visual analogue scale of pain, tender joint count, Ritchie articular index or C-reactive protein, but not with anti-nuclear antibody or rheumatoid factor. These results suggest that anti-filaggrin antibody recognizes the uncitrullinated filaggrin as an antigen and its titer correlates with clinical parameters, explaining the variable sensitivity of anti-filaggrin antibody test.
Amino Acid Sequence ; Antibodies/*blood/*immunology ; Arthritis, Rheumatoid/blood/*diagnosis/*immunology ; Case-Control Studies ; Citrulline/*analysis ; Humans ; Intermediate Filament Proteins/*chemistry/*immunology/isolation & purification ; Molecular Sequence Data ; Research Support, Non-U.S. Gov't

BACKGROUND: The presence of rheumatoid factor (RF) is one of the classification criteria of the American College of Rheumatology (ACR) for rheumatoid arthritis (RA), but it has a limitation of low specificity. We compared the diagnostic utility of anti-cyclic citrullinated peptide (CCP) antibodies analyzed by an automated immunoassay system with that measured by a 96 well plate ELISA method. METHODS: The RF and anti-CCP antibodies were determined in 172 serum samples: 52 RA patients, 73 disease controls (systemic lupus, Sjogren's syndrome, palindromic rheumatism), and 47 healthy controls. Anti-CCP antibodies were measured by DIASTAT 96 well plate ELISA method (Axis-Shield Diagnostics, UK) and AxSYM automated microparticle enzyme immunoassay system (Abbott Laboratories, USA). RF was assayed by latex immunoturbidimetry (Toshiba 200 FR, Japan). The diagnostic performances of these tests were compared using a ROC curve analysis, and linearity and precision analysis of AxSYM anti-CCP was carried out. RESULTS: The sensitivities of RF, DIASTAT anti-CCP, and AxSYM anti-CCP were 78.8%, 84.6%, and 82.7%, respectively and the specificities were 72.5%, 88.3%, and 88.3%, respectively. On ROC curve analysis, the area under the curve was 0.924 for AxSYM anti-CCP, 0.886 for DIASTAT anti-CCP, and 0.847 for RF. AxSYM anti-CCP showed a good linearity, and within-run and total-run precision. CONCLUSIONS: Diagnostic performance of automated AxSYM anti-CCP assay was comparable to that of DIASTAT 96 well plate ELISA method. AxSYM anti-CCP assay has an advantage of random access capability and will be useful in laboratories with low sample number and/or with a need of rapid turnaround time.
Adolescent ; Adult ; Aged ; Arthritis, Rheumatoid/*diagnosis ; Autoantibodies/*blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; *Immunoenzyme Techniques ; Male ; Middle Aged ; Peptides, Cyclic/*immunology ; ROC Curve ; Reagent Kits, Diagnostic ; Rheumatoid Factor/blood ; Sensitivity and Specificity

BACKGROUND/AIMS: To examine the correlation between radiological joint damage and serological parameters in early rheumatoid arthritis (RA). METHODS: This retrospective study reviewed the records of 216 patients diagnosed with RA and classified them according to disease duration: group 1, < or = 24 months; group 2, > 24 months; and group 3, all patients combined. The extent of joint damage was assessed from plain radiographs using a modified version of the Larsen method and compared among groups. RESULTS: The mean radiographic joint damage score was significantly higher in patients who had established RA (10.1 points) compared with those who had early RA. In group 1, the inflammatory parameters, erythrocyte sedimentation rate, and C-reactive protein were positively correlated with the joint damage score, but rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody were not. A subgroup analysis revealed that the anti-CCP positive patients in groups 1 and 2 had greater joint damage scores than did the anti-CCP negative patients, but no difference in RF was observed between subgroups. Anti-CCP positivity was not significantly correlated with joint damage sores in group 3. CONCLUSIONS: Anti-CCP positivity was significantly correlated with more severe joint damage at diagnosis. A correlation was observed between the radiological joint damage score and inflammatory parameters in early and established RA, indicating that anti-CCP can serve as a diagnostic tool and predict structural joint damage. These findings suggest anti-CCP positive patients should receive aggressive therapeutic intervention.
Adult ; Arthritis, Rheumatoid/*immunology/*radiography ; Autoantibodies/*blood ; *Biological Markers ; Early Diagnosis ; Female ; Finger Joint/radiography ; Humans ; Male ; Metacarpophalangeal Joint/radiography ; Middle Aged ; Peptides, Cyclic/*immunology ; Retrospective Studies ; Severity of Illness Index ; Wrist Joint/radiography

BACKGROUND/AIMS: Increased resting energy expenditure (REE) in rheumatoid arthritis (RA) patients is thought to be caused by hypermetabolism associated with production of proinflammatory cytokines. Our aim in the present study was to explore the possible association between REE and disease activity in females with RA. METHODS: A total of 499 female RA patients were recruited to this cross-sectional study assessing REE scores on disease activity indices (the routine assessment of patient index data 3 [RAPID3], the disease activity score 28, and the clinical/simplified disease activity index [CDAI/SDAI]) and the levels of RA-associated autoantibodies (rheumatoid factor and anticyclic citrullinated peptide [anti-CCP] antibodies). Age-matched healthy female controls (n = 131) were also enrolled. RESULTS: REE did not differ between RA patients (all patients, and those in remission or not) and controls, or between RA patients in remission or not (p > 0.05 for all comparisons). Increased REE in total RA patients was associated with younger age and a higher body mass index (BMI) (p < 0.001 and p < 0.001, respectively), but not with disease activity index scores on any of RAPID3, CDAI, or SDAI. BMI was the only clinical parameter exhibiting a significant relationship with REE quartiles (Q1 to Q4; p < 0.001); none of disease duration, functional status, or anti-CCP antibody titer in RA patients was significantly related to REE, based on analysis of covariance. CONCLUSIONS: We found no association between REE and disease activity in RA patients, implying that energy metabolism in RA patients might be independent of RA-associated systemic inflammation.
Adult ; Age Factors ; Aged ; Arthritis, Rheumatoid/blood/diagnosis/*metabolism/physiopathology ; Biological Markers/blood ; Body Mass Index ; Case-Control Studies ; Cross-Sectional Studies ; *Energy Metabolism ; Female ; Humans ; Inflammation Mediators/blood ; Middle Aged ; Peptides, Cyclic/immunology ; Predictive Value of Tests ; *Rest ; Rheumatoid Factor/blood ; Severity of Illness Index