INTRODUCTION: Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) are used in the diagnosis and prognostication of rheumatoid arthritis (RA). We wanted to determine the specific contributions of RF and ACPA to the biological nature of RA and whether they act synergistically. METHODS: We identified 731 patients from our prospective multi-ethnic RA cohort and categorised them into four groups: ACPA-positive, RF-positive, doubly positive and doubly negative. We compared the demographics, Disease Activity Score-28, Health Assessment Questionnaire score, quality of life using Short Form 36 and the use of prednisolone and disease-modifying antirheumatic drugs (DMARDs) of these patient groups. RESULTS: Four hundred and ninety-one patients (67.2%) were ACPA+RF+, 54 (7.4%) were ACPA+RF-, 82 (11.2%) were ACPA-RF+ and 104 (14.2%) were ACPA-RF-. Mean disease duration before the study entry was not different in the four groups. Patients with older age of onset were less likely to be positive for RF and ACPA. Fewer ACPA+RF+ patients were in remission compared to those in the other groups ( P < 0.05). Erythrocyte sedimentation rate (ESR) was higher at study entry in the ACPA+RF+ group (40.4 mm/h vs. 30.6-30.9 mm/h, P < 0.05). Prednisolone and number of DMARDs used were higher in the ACPA+RF+ group compared to the doubly negative group. There were no differences in the functional status and quality of life. CONCLUSIONS RA patients who were positive for both ACPA and RF had lower remission rate, higher baseline ESR and required more corticosteroid and DMARD treatment compared to those who were singly positive or doubly negative. Being doubly positive confers a worse outcome to RA patients.
Humans ; Arthritis, Rheumatoid/diagnosis* ; Male ; Female ; Middle Aged ; Rheumatoid Factor/blood* ; Anti-Citrullinated Protein Antibodies/blood* ; Adult ; Quality of Life ; Prospective Studies ; Antirheumatic Agents/therapeutic use* ; Aged ; Peptides, Cyclic/immunology* ; Prednisolone/therapeutic use* ; Surveys and Questionnaires ; Severity of Illness Index ; Prognosis

Objective Based on 25 indicators including immune factors, cell count classification, and smear results of the knee joint fluid, machine learning models were established to distinguish between osteoarthritis (OA) and rheumatoid arthritis (RA). Methods 100 OA and 40 RA patients scheduled for total knee arthroplasty were enrolled respectively. Each patient's knee joint fluid was collected preoperatively. Nucleated cells were counted and classified. The expression levels of immune factors, including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, IL-8, IL-15, matrix metalloproteinase 3 (MMP3), MMP9, MMP13, rheumatoid factor (RF), serum amyloid A (SAA), C-reactive protein (CRP), and others were measured. Smears and microscopic classification of all the immune factors were performed. Independent influencing factors for OA or RA were identified using univariate binary logistic regression, Lasso regression, and multivariate binary logistic regression. Based on the independent influencing factors, three machine learning models were constructed which are logistic regression, random forest, and support vector machine. Receiver operating characteristic curve (ROC), calibration curve and decision curve analysis (DCA) were used to evaluate and compare the models. Results A total of 5 indicators in the knee joint fluid were screened out to distinguish OA and RA, which were IL-1β(odds ratio(OR)=10.512, 95× confidence interval (95×CI) was 1.048-105.42, P=0.045), IL-6 (OR=1.007, 95×CI was 1.001-1.014, P=0.022), MMP9 (OR=3.202, 95×CI was 1.235-8.305, P=0.017), MMP13 (OR=1.002, 95× CI was 1-1.004, P=0.049), and RF (OR=1.091, 95×CI was 1.01-1.179, P=0.026). According to the results of ROC, calibration curve and DCA, the accuracy (0.979), sensitivity (0.98) and area under the curve (AUC, 0.996, 95×CI was 0.991-1) of the random forest model were the highest. It has good validity and feasibility, and its distinguishing ability is better than the other two models. Conclusion The machine learning model based on immune factors in the knee joint fluid holds significant value in distinguishing OA and RA. It provides an important reference for the clinical early differential diagnosis, prevention and treatment of OA and RA.
Humans ; Arthritis, Rheumatoid/metabolism* ; Machine Learning ; Male ; Female ; Middle Aged ; Aged ; Synovial Fluid/immunology* ; Osteoarthritis, Knee/metabolism* ; Knee Joint/metabolism* ; ROC Curve ; Diagnosis, Differential

Objective To explore the expression of coagulation indexes in rheumatoid arthritis (RA) and dry syndrome (pSS) and their relationships with inflammation and immune function. Methods A total of 61 patients with RA who were hospitalized in the Department of Rheumatology of Anhui Provincial Hospital of Traditional Chinese Medicine from March 12 to September 9, 2024 were selected as the RA group. And 61 patients with pSS who were hospitalized in the Department of Rheumatology of the same hospital September 4, 2023, to August 17, 2024, were selected as the pSS group. 61 healthy individuals who underwent routine medical checkups at the Physical Examination Center of Anhui Provincial Hospital of Traditional Chinese Medicine during the same period were included as the control group. Baseline clinical indexes before treatment were collected from patients in each group, including prothrombin time(PT), international normalized ratio(INR), thrombia time(TT), fibrinogen(FBG), activated partial thromboplastin time(APTT), fibrin (ogen) degradation products(FDP) and D-Dimer(D-D). Results The expression levels of PT, FBG, TT, FDP, and D-D in the RA group, the pSS group, and the normal group were significantly different. The expression levels of PT, FBG, FDP, and D-D in the RA group were all higher than those in the pSS group and the control group, respectively. And the expression level of TT in the pSS group was lower than that in control group. ROC curve analysis showed that the AUC of PT was 0.638, the AUC of FBG was 0.899, the AUC of FDP was 0.866, and the AUC of D-D was 0.919 in the RA group compared with the normal group. And the AUC of coagulation indexes for joint diagnosis of RA was higher than that of the indexes detected individually. pSS group had an AUC of PT of 0.618 compared with that of the normal group. The AUC of TT was 0.645, and the AUC of coagulation indexes for the joint diagnosis of pSS was higher than the AUC of each index detected separately. Association rule analysis showed that elevated D-D in RA patients had a significant correlation with elevated hs-CRP, CCP and RF, and elevated FBG had a significant correlation with elevated hs-CRP, ESR, RF and CCP. Elevated D-D in pSS patients had a correlation with elevated hs-CRP and anti-SSA, and elevated INR has correlation with elevated hs-CRP, anti-SSA and anti-SSB. Correlation analysis showed that PT, INR, FBG, FDP, and D-D were positively correlated with CRP and ESR, and TT was negatively correlated with CRP and ESR in the RA group. FBG, FDP, and D-D were positively correlated with CRP and ESR in the pSS group. Moreover, coagulation indexes were positively correlated with immune indexes in RA group and pSS group which were all significant. The results of multiple linear regression analysis showed that FBG was a positive correlate of hs-CRP and ESR in RA patients. For PSS patients, FBG and FDP were positive correlates of hs-CRP. APTT and FBG were positive correlates of ESR. Conclusion Compared with pSS, coagulation indexes (especially PT, FBG, FDP and D-D) are more informative for the early diagnosis of RA and the judgment of the degree of the disease, and can be used as an important predictor for the confirmation of the diagnosis of RA.
Humans ; Female ; Male ; Arthritis, Rheumatoid/diagnosis* ; Middle Aged ; Fibrin Fibrinogen Degradation Products/analysis* ; Blood Coagulation ; Adult ; Fibrinogen/metabolism* ; Partial Thromboplastin Time ; Prothrombin Time ; Aged ; Inflammation/immunology* ; ROC Curve

We aimed to investigate the value of bone scintigraphy with additional blood pool phase (BSBP), compared with conventional bone scintigraphy (CBS), in the assessment of rheumatoid arthritis (RA). A total of 242 patients (43 males, 199 females; 14-78 years) with arthralgia, and underwent BSBP were retrospectively analyzed. On the first physical examination, active arthritis was found in 128 of the 242 patients. Clinical diagnosis was made by a rheumatologist on the basis of the 1987 American College of Rheumatology (ACR) criteria, which are considered to be the gold standard. The diagnostic performances and prognostic value of BSBP and CBS were analyzed in the total patients with arthralgia and in the patients with arthritis. The sensitivity of BSBP (84.2%, 80/95) were significantly higher than that of CBS (74.8%, 72/95) in the patients with arthralgia (P = 0.039). When BSBP was interpreted with the results of elevated/positive anti-CCP antibody, its accuracy over CBS also became significantly higher (86.0%, 208/242 vs. 83.1%, 201/242 respectively, P = 0.021). The diagnostic odds ratio of BSBP positivity was higher than CBS positivity in the patients with arthralgia (26.0, 12.9-52.4 vs. 21.1, 10.8-41.3) and with arthritis (12.0, 4.9-29.4 vs. 10.0, 4.2-23.4). Both BSBP and CBS appear to provide acceptable accuracy and comparable diagnostic performance for diagnosis of RA. However, in the patients with arthralgia, BSBP was found to be more sensitive than CBS and more accurate when interpreted with the result of anti-CCP antibody. This could help physicians diagnose RA in daily clinical practice.
Adolescent ; Adult ; Aged ; Arthralgia/complications ; Arthritis, Rheumatoid/complications/*diagnosis ; Autoantibodies/blood ; Bone and Bones/diagnostic imaging ; Female ; *Gated Blood-Pool Imaging ; Humans ; Male ; Middle Aged ; Odds Ratio ; Peptides, Cyclic/immunology ; Positron-Emission Tomography ; Prognosis ; Retrospective Studies ; Sensitivity and Specificity ; Technetium/chemistry ; *Tomography, X-Ray Computed ; Young Adult

BACKGROUND/AIMS: To evaluate the impact on mortality of anti-tumor necrosis factor (anti-TNF) treatment of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: We retrospectively reviewed the medical records of 100 RA-ILD patients who visited our tertiary care medical center between 2004 and 2011, identified those treated with an anti-TNF agent, divided patients into non-survivor and survivor groups and evaluated their clinical characteristics and causes of death. RESULTS: A total of 24 RA-ILD patients received anti-TNF therapy, of whom six died (25%). Mean age at initiation of anti-TNF therapy was significantly higher in the nonsurvivor versus survivor group (76 years [range, 66 to 85] vs. 64 years [range, 50 to 81], respectively; p = 0.043). The mean duration of anti-TNF treatment in the non-survivor group was shorter (7 months [range, 2 to 14] vs. 23 months [range, 2 to 58], respectively; p = 0.030). The duration of anti-TNF therapy in all nonsurviving patients was < 12 months. Pulmonary function test results at ILD diagnosis, and cumulative doses of disease-modifying drugs and steroids, did not differ between groups. Five of the six deaths (83%) were related to lung disease, including two diffuse alveolar hemorrhages, two cases of acute exacerbation of ILD, and one of pneumonia. The sixth patient died of septic shock following septic arthritis of the knee. CONCLUSIONS: Lung complications can occur within months of initial anti-TNF treatment in older RA-ILD patients; therefore, anti-TNF therapy should be used with caution in these patients.
Adult ; Aged ; Aged, 80 and over ; Antirheumatic Agents/adverse effects/*therapeutic use ; Arthritis, Rheumatoid/complications/diagnosis/*drug therapy/immunology/mortality ; Female ; Humans ; Lung Diseases, Interstitial/diagnosis/etiology/*mortality ; Male ; Middle Aged ; Republic of Korea ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Tertiary Care Centers ; Time Factors ; Treatment Outcome ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors

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

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 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

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