1.Dual rheumatoid factor and anti-cyclic citrullinated peptide antibody positivity affects the manifestations of rheumatoid arthritis.
Li Huan Angela Marie CHAN ; Khai Pang LEONG ; Justina Wei Lynn TAN ; Xiao GAO ; Wei Qiang SEE ; Ee Tzun KOH
Singapore medical journal 2025;66(9):486-491
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
2.Coagulation profile PT, FBG, FDP, D-D as disease predictors of RA and pSS inflammatory immunity.
Wenwen MIN ; Lei WAN ; Feng LI ; Yu ZHANG ; Ying WANG ; Siyu LIANG
Chinese Journal of Cellular and Molecular Immunology 2025;41(10):895-904
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
3.Osseous changes in the temporomandibular joint in rheumatoid arthritis: A cone-beam computed tomography study
Ola Mohamed REHAN ; Hoda Abdel Kader SALEH ; Hala Ahmed RAFFAT ; Noha Saleh ABU-TALEB
Imaging Science in Dentistry 2018;48(1):1-9
PURPOSE: To evaluate osseous changes of temporomandibular joint (TMJ) in patients with rheumatoid arthritis (RA) using cone-beam computed tomography (CBCT) and to correlate the imaging findings with the severity of TMJ dysfunction, clinical findings, and laboratory findings. MATERIALS AND METHODS: This study consisted of 28 subjects, including 14 RA patients and 14 controls, who were scheduled to undergo CBCT imaging for the diagnosis of a complaint not related to or affecting the TMJ. The Fonseca's questionnaire was used to assess the severity of TMJ dysfunction. Rheumatoid factor (RF) and the erythrocyte sedimentation rate (ESR) were assessed in the RA patients. CBCT was then performed in all subjects and osseous TMJ abnormalities were assessed. RESULTS: According to the Fonseca's questionnaire, 14.3% of the patients had no TMJ dysfunction, while 50%, 21.4%, and 14.3% had mild, moderate, and severe dysfunction, respectively. RF was positive in 64.3% of patients, and the ESR level was high in 100%. Imaging findings revealed a statistically significantly higher prevalence of erosion (85.7%), flattening (89.3%), osteophyte formation (32.1%), subchondral cyst (32.1%), sclerosis (64.3%), and condylar irregularities (28.6%) in the RA patients than in the controls. No correlations were found between CBCT findings and the clinical findings, the severity of TMJ dysfunction, disease duration, or laboratory results. CONCLUSION: RA patients might show extensive osseous abnormalities with no/mild clinical signs or symptoms of TMJ dysfunction that necessitate TMJ imaging for these patients. CBCT is a valuable and efficient modality that can assess osseous TMJ changes in RA patients.
Arthritis, Rheumatoid
;
Blood Sedimentation
;
Bone Cysts
;
Cone-Beam Computed Tomography
;
Diagnosis
;
Humans
;
Osteophyte
;
Prevalence
;
Rheumatoid Factor
;
Sclerosis
;
Temporomandibular Joint
4.Value of serum matrix metalloproteinase 3 in the assessment of early rheumatoid arthritis.
Meng Ke LIU ; Lu Chen WANG ; Fan Lei HU
Journal of Peking University(Health Sciences) 2018;50(6):981-985
OBJECTIVE:
To investigate the expression level of serum matrix metalloproteinase 3 (MMP3) in early rheumatoid arthritis (ERA) patients with normal C-reaction protein (CRP) or erythrocyte sedimentation rate (ESR), and the significance in disease assessment.
METHODS:
In the study, 133 cases of early RA patients, 25 osteoarthritis (OA) patients and 60 healthy controls in Peking University People's Hospital from 2011 to 2015 were included. The RA patients were further divided into 4 groups according to levels of CRP and ESR: 88 patients with increased CRP and increased ESR, 15 patients with normal CRP and normal ESR, 17 patients with normal CRP but increased ESR, and 13 patients with increased CRP but normal ESR. All the clinical information of the patients was collected, and the serum MMP3 levels of both patients and healthy controls were detected by enzyme-linked immune sorbent assay (ELISA).
RESULTS:
The serum MMP3 level of RA patients with normal CRP and/or normal ESR [(72.89±6.34) μg/L] was obviously higher than that of OA patients [(42.87±4.14) μg/L] (P=0.002) and healthy controls [(31.62±2.88) μg/L] (P<0.001). The serum MMP3 levels of the patients with normal CRP and normal ESR [(47.04±9.64) μg/L] were higher than those of the healthy controls, and there was statistical significance between the two groups (P<0.05). The serum MMP3 levels of the patients with increased CRP but normal ESR [(94.18±9.11) μg/L] and the patients with normal CRP but increased ESR [(79.42±10.60) μg/L] were both higher than those of the OA patients and healthy controls, and there was obvious statistical difference (P<0.05). In the early RA patients with normal CRP and/or normal ESR, the serum MMP3 level was positively correlated with the CRP level (r=0.336, P=0.024). The positive rate of MMP3 in the patients with normal CRP and/or normal ESR was 44.44%, higher than the positive rate of CRP (28.89%) and the positive rate of ESR (37.78%). In these early RA patients, the positive rate was 52.94% in the patients with normal CRP but increased ESR and 53.85% in the patients with increased CRP but normal ESR.
CONCLUSION
The detection of the serum MMP3 level was significant in the assessment of early RA patients within 2-year duration who had normal CRP or ESR value.
Arthritis, Rheumatoid/diagnosis*
;
Blood Sedimentation
;
Humans
;
Matrix Metalloproteinase 3/blood*
;
Osteoarthritis
5.Bone Scintigraphy in the Diagnosis of Rheumatoid Arthritis: Is There Additional Value of Bone Scintigraphy with Blood Pool Phase over Conventional Bone Scintigraphy?.
Ji Young KIM ; Yun Young CHOI ; Chan Woo KIM ; Yoon Kyoung SUNG ; Dae Hyun YOO
Journal of Korean Medical Science 2016;31(4):502-509
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
6.Atypical Wegener's Granulomatosis Accompanied with Rheumatoid Arthritis: A Case Report.
Laboratory Medicine Online 2015;5(3):161-164
Wegener's granulomatosis (WG) is highly correlated with cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA). Patients with rheumatoid arthritis (RA) rarely contract WG. Although several concurrent cases have been reported overseas, there are no known cases in Korea. Here we report a unique case of RA with atypical WG testing positive for perinuclear ANCA (p-ANCA) and negative for anti-myeloperoxidase (MPO) antibodies. The 62-yr-old female patient presented with multiple joint pain and showed typical blood test results for RA, i.e., an elevated erythrocyte sedimentation rate and C-reactive protein concentration, and positive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies. RA was clear based on a total score of 10 when applying the classification criteria developed by the American College of Rheumatology/European League Against Rheumatism (2010). In an autoimmune target test, speckled and skeleton patterns were observed. In an ANCA test, p-ANCA was observed (titer, 1:2,560), and tests for anti-proteinase 3 (PR3) and anti-MPO antibodies were negative. After admission, multiple nodules were detected on a chest X-ray and a computed tomography scan. We suspected that she had rheumatic nodules or vasculitis and performed an open lung biopsy. We detected necrotic granulomatous vasculitis, classified as WG, thus leading to WG diagnosis. In conclusion, WG was diagnosed in an RA patient who was negative for c-ANCA (negative PR3) and positive for p-ANCA (negative anti-MPO), and this peculiar finding is likely to improve diagnosis in cases of RA with atypical WG.
Antibodies
;
Antibodies, Antineutrophil Cytoplasmic
;
Arthralgia
;
Arthritis, Rheumatoid*
;
Biopsy
;
Blood Sedimentation
;
C-Reactive Protein
;
Classification
;
Cytoplasm
;
Diagnosis
;
Female
;
Hematologic Tests
;
Humans
;
Korea
;
Lung
;
Rheumatic Diseases
;
Rheumatic Nodule
;
Rheumatoid Factor
;
Skeleton
;
Thorax
;
Vasculitis
;
Wegener Granulomatosis*
7.Rhupus syndrome.
Jae Ki MIN ; Kyoung Ann LEE ; Hae Rim KIM ; Ho Youn KIM ; Sang Heon LEE
The Korean Journal of Internal Medicine 2015;30(1):131-131
No abstract available.
Antirheumatic Agents/therapeutic use
;
Arthritis, Rheumatoid/blood/*complications/diagnosis/drug therapy/physiopathology
;
Biological Markers/blood
;
Drug Therapy, Combination
;
Facial Dermatoses/complications/diagnosis
;
Female
;
Hand Joints/physiopathology/radiography
;
Humans
;
Immunosuppressive Agents/therapeutic use
;
Inflammation Mediators/blood
;
Knee Joint/physiopathology/radiography
;
Lupus Erythematosus, Systemic/blood/*complications/diagnosis/drug therapy
;
Middle Aged
;
Syndrome
;
Treatment Outcome
8.Assessment of Peripheral Neuropathy in Patients With Rheumatoid Arthritis Who Complain of Neurologic Symptoms.
Mi Kyung SIM ; Dae Yul KIM ; Jisun YOON ; Dae Hwan PARK ; Yong Gil KIM
Annals of Rehabilitation Medicine 2014;38(2):249-255
OBJECTIVE: To assess the prevalence of peripheral neuropathy in patients with rheumatoid arthritis (RA) having neuropathic symptoms, and to investigate the relationship between electrophysiological findings of peripheral neuropathy and clinical findings of RA. METHODS: Patients with a clinical diagnosis of RA and who had tingling or burning sensation in any extremity were electrophysiologically examined for evidence of peripheral neuropathy. Study parameters, including age, gender, laboratory parameters, duration of RA, and medication, were recorded. The symptoms and signs of neuropathy were quantified with the neuropathy symptom score, and the functional statuses of these patients were assessed. RESULTS: Out of a total of 30 RA patients, 10 (33%) had peripheral neuropathy: 2 had bilateral carpal tunnel syndrome (CTS), 5 had unilateral CTS, 1 had sensory polyneuropathy, and 2 had motor-sensory polyneuropathy. The mean ages of the patients with and without peripheral neuropathy were 69.4 and 56.5 years, respectively (p<0.05). A significant relationship was found between peripheral neuropathy and anti-cyclic citrullinated peptide (anti-CCP) antibody. However, no relationship was found between peripheral neuropathy and the type of medication, RA duration, the patients' functional status, neuropathic symptoms, erythrocyte sedimentation rate, and C-reactive protein values. CONCLUSION: Neuropathic symptoms are common in RA patients, and it is difficult to distinguish peripheral neuropathy symptoms from those of arthritis. Patients with RA, particularly elderly patients and anti-CCP antibody positive patients who complain of neuropathic symptoms should undergo electrophysiological examination.
Aged
;
Arthritis
;
Arthritis, Rheumatoid*
;
Blood Sedimentation
;
Burns
;
C-Reactive Protein
;
Carpal Tunnel Syndrome
;
Diagnosis
;
Extremities
;
Humans
;
Neurologic Manifestations*
;
Peripheral Nervous System Diseases*
;
Polyneuropathies
;
Prevalence
;
Sensation
9.Assessment of Peripheral Neuropathy in Patients With Rheumatoid Arthritis Who Complain of Neurologic Symptoms.
Mi Kyung SIM ; Dae Yul KIM ; Jisun YOON ; Dae Hwan PARK ; Yong Gil KIM
Annals of Rehabilitation Medicine 2014;38(2):249-255
OBJECTIVE: To assess the prevalence of peripheral neuropathy in patients with rheumatoid arthritis (RA) having neuropathic symptoms, and to investigate the relationship between electrophysiological findings of peripheral neuropathy and clinical findings of RA. METHODS: Patients with a clinical diagnosis of RA and who had tingling or burning sensation in any extremity were electrophysiologically examined for evidence of peripheral neuropathy. Study parameters, including age, gender, laboratory parameters, duration of RA, and medication, were recorded. The symptoms and signs of neuropathy were quantified with the neuropathy symptom score, and the functional statuses of these patients were assessed. RESULTS: Out of a total of 30 RA patients, 10 (33%) had peripheral neuropathy: 2 had bilateral carpal tunnel syndrome (CTS), 5 had unilateral CTS, 1 had sensory polyneuropathy, and 2 had motor-sensory polyneuropathy. The mean ages of the patients with and without peripheral neuropathy were 69.4 and 56.5 years, respectively (p<0.05). A significant relationship was found between peripheral neuropathy and anti-cyclic citrullinated peptide (anti-CCP) antibody. However, no relationship was found between peripheral neuropathy and the type of medication, RA duration, the patients' functional status, neuropathic symptoms, erythrocyte sedimentation rate, and C-reactive protein values. CONCLUSION: Neuropathic symptoms are common in RA patients, and it is difficult to distinguish peripheral neuropathy symptoms from those of arthritis. Patients with RA, particularly elderly patients and anti-CCP antibody positive patients who complain of neuropathic symptoms should undergo electrophysiological examination.
Aged
;
Arthritis
;
Arthritis, Rheumatoid*
;
Blood Sedimentation
;
Burns
;
C-Reactive Protein
;
Carpal Tunnel Syndrome
;
Diagnosis
;
Extremities
;
Humans
;
Neurologic Manifestations*
;
Peripheral Nervous System Diseases*
;
Polyneuropathies
;
Prevalence
;
Sensation
10.Early effects of tumor necrosis factor inhibition on bone homeostasis after soluble tumor necrosis factor receptor use.
Mie Jin LIM ; Seong Ryul KWON ; Kowoon JOO ; Min Jung SON ; Shin Goo PARK ; Won PARK
The Korean Journal of Internal Medicine 2014;29(6):807-813
BACKGROUND/AIMS: Our aim was to assess whether short-term treatment with soluble tumor necrosis factor (TNF) receptor affects circulating markers of bone metabolism in rheumatoid arthritis (RA) patients. METHODS: Thirty-three active RA patients, treated with oral disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids for > 6 months, were administered etanercept for 12 weeks. Serum levels of bone metabolism markers were compared among patients treated with DMARDs at baseline and after etanercept treatment, normal controls and naive RA patients not previously treated with DMARDs (both age- and gender-matched). RESULTS: Bone-specific alkaline phosphatase (BSALP) and serum c-telopeptide (CTX)-1 levels were lower in RA patients treated with DMARDs than in DMARD-naive RA patients. After 12 weeks of etanercept treatment, serum CTX-1 and sclerostin levels increased. In patients whose DAS28 improved, the sclerostin level increased from 1.67 +/- 2.12 pg/mL at baseline to 2.51 +/- 3.03 pg/mL, which was statistically significant (p = 0.021). Increases in sclerostin levels after etanercept treatment were positively correlated with those of serum CTX-1 (r = 0.775), as were those of BSALP (r = 0.755). CONCLUSIONS: RA patients treated with DMARDs showed depressed bone metabolism compared to naive RA patients. Increases in serum CTX-1 and sclerostin levels after short-term etanercept treatment suggest reconstitution of bone metabolism homeostasis.
Adult
;
Alkaline Phosphatase/blood
;
Arthritis, Rheumatoid/blood/diagnosis/*drug therapy
;
Biological Markers/blood
;
Bone Morphogenetic Proteins/blood
;
Bone Remodeling/*drug effects
;
Collagen Type I/blood
;
Female
;
Genetic Markers
;
Homeostasis
;
Humans
;
Immunoglobulin G/*administration & dosage
;
Immunosuppressive Agents/*administration & dosage
;
Inflammation Mediators/blood
;
Male
;
Middle Aged
;
Peptides/blood
;
Receptors, Tumor Necrosis Factor/*administration & dosage
;
Time Factors
;
Treatment Outcome
;
Tumor Necrosis Factor-alpha/antagonists & inhibitors

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