Health-related Quality of Life Outcomes of Adalimumab for Patients With Rheumatoid Arthritis in Korea

Objective@#Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune disorder that impairs patients’ overall health-related quality of life (HRQOL). In this study, we evaluated the effect of adalimumab in Korean patients with active RA on HRQOL. @*Methods@#Patients included in the study had moderate to severe active RA that did not respond to conventional drugs with a Disease Activity Score of 28 joints ＞3.2 and were biologics-naïve. All patients received adalimumab 40 mg subcutaneously every other week and were followed for 24 weeks. The primary endpoint was the change in baseline Health Assessment Questionnaire Disability Index (HAQ-DI) score at week 24. Secondary endpoints were changes in the EuroQol 5-dimension 3-Level (EQ-5D-3L) baseline score and Short Form 36-Item Health Survey (SF-36) domain scores at weeks 12 and 24 and change in baseline HAQ-DI score at week 12. @*Results@#In total, 91 Korean patients were included. Ninety-three percent of patients were in high disease activity with a baseline mean DAS28 value of 6.1 within all patients. The mean change from baseline in HAQ-DI scores were −0.46 at week 12 and∼0.67 at week 24 (p＜0.0001). Additionally, EQ-5D-3L score at weeks 12 and 24 had significantly improved (p＜0.0001) compared to baseline. SF-36 at weeks 12 and 24 had significantly improved (p＜0.0001, p=0.0001) compared to baseline. @*Conclusion@#Treatment with adalimumab resulted in significant improvement in HAQ-DI, EQ-5D-3L, and SF-36 scores at 12 and 24 weeks in Korean RA patient.

Long-term Treatment with Anti-platelet Agents for Collagen-induced Arthritis Improves Radiological Findings

OBJECTIVES: The objectives of this study were to evaluate the long-term effect of anti-platelet treatment on the radiological progression of collagen-induced arthritis in rats. METHODS: Female Lewis rats with collagen-induced arthritis were divided into three experimental groups: saline, aspirin monotherapy (n = 12), and aspirin–clopidogrel dual therapy (n = 12). Drugs were administered daily and continued up to 70 days after the induction of arthritis. The clinical arthritis index (weight, morphology score, and paw thickness) and radiological scores were evaluated. RESULTS: The clinical arthritis index peaked on day 20, while the radiological scores peaked on day 35. No intergroup difference was observed in the clinical arthritis index throughout the experiment. The aspirin–clopidogrel dual therapy group had a significantly higher mean radiological score than the other groups (p = 0.045) on day 35. Further treatments resulted in significantly improved radiological findings in the aspirin monotherapy and aspirin–clopidogrel dual therapy groups on day 70 but no significant improvement in the saline group. CONCLUSION: Anti-platelet agent treatment improved radiological findings on day 70. These observations emphasize the importance of a future long-term study of the effects of anti-platelet agent treatment on arthritis.

ADAM33 Polymorphisms Are Associated with Susceptibility to Systemic Lupus Erythematosus in a Korean Population

OBJECTIVE: The objective of this study is to assess whether genetic functional variants of disintegrin and metalloprotease 33 (ADAM33) are associated with susceptibility to systemic lupus erythematosus (SLE) in a Korean population. METHODS: We previously identified 48 single nucleotide polymorphisms (SNPs) in ADAM33. Six SNPs were selected with regard to the linkage disequilibrium pattern. An association study of ADAM33 was conducted in 190 patients with SLE and 469 control subjects. SNPs were genotyped using the TaqMan Real-time polymerase chain reaction method, and haplotype analyses of related variants were performed. RESULTS: All SNPs were in Hardy-Weinberg equilibrium. Significant associations were found between the ADAM33 polymorphisms and SLE at rs2787094 (adjusted odds ratio [OR] 1.88, 95% confidence interval [CI] 1.00 to 3.54; p<0.0001). The rs554743 polymorphism was associated with the presence of the immunoglobulin M anti-cardiolipin antibody (adjusted OR 0.29, 95% CI 0.10 to 0.83; p=0.021). CONCLUSION: ADAM33 polymorphisms were associated with susceptibility to SLE and development of clinical disease manifestations in a Korean population. Further study is warranted to clarify the role of ADAM33 in SLE pathogenesis.

A Case of Guillain-Barre Syndrome in a Patient of Behcet's Disease

Behcet's disease (BD) is a multi-systemic inflammatory disease of unknown origin that affects nearly all organs including the nervous system. Although the neurological involvement is less frequent than other major presentations, it is important because it can produce severe disabilities. Peripheral nervous system manifestations are relatively rare in BD. Although few cases of peripheral neuropathy or myopathy have been reported in BD, they are cases of multiple neuropathies, sensorimotor peripheral neuropathy, or neuropathy autonomic dysfunction. Guillain-Barre syndrome (GBS), also known as an acute inflammatory demyelinating polyneuropathy, is an acute demyelinating polyradiculopathy of uncertain etiology. No case of GBS associated with BD in Korea has been reported. Herein we report on a patient of BD who suffered from weakness of extremities and was diagnosed as GBS.

Withdrawal: Animal Models in Systemic Lupus Erythematosus

This article has been retracted.

Prediction for TNF Inhibitor Users in RA Patients According to Reimbursement Criteria Based on DAS28

OBJECTIVE: The purpose of this study is to examine the difference between the numbers of patients in rheumatoid arthritis (RA) who are eligible to TNF inhibitors by the past Korean National Health Insurance reimbursement guideline and by the disease activity score with 28-joint assessment (DAS28) based criteria. METHODS: Data were obtained from a multi-center registry for biologics users in Korean RA patients, BIOlogics Pharmacoepidemiologic StudY (BIOPSY). DAS28 was calculated based on either ESR or CRP, and DAS28 of more than 5.1 or between 3.2 and 5.1 with radiographic changes was defined as a cut-off point for the initiation of TNF inhibitors. For the maintenance criteria, we used both of improving in DAS28 score (>1.2) and low disease activity (DAS 28<3.2). Differences between the numbers in each step by two criteria were described with Chi-square test and Kappa agreement. RESULTS: Of the 489 patients in BIOPSY, 299 were included in this study. Among them, 278 patients (93.0%) were eligible of TNF inhibitors when we applied the new initiation criteria with DAS28-ESR, and 244 patients (81.6%) were indicated for TNF inhibitors with DAS28-CRP. For the maintenance criteria, a low disease activity (DAS28<3.2) in 3 months after starting TNF inhibitors is too strict for achieving (33.6% with DAS28-ESR and 50.0% with DAS28-CRP). Instead, decreasing DAS28 by more than 1.2 is more reasonable as a tool for deciding early responsiveness of TNF inhibitors in RA patients (81.2% both with DAS28-ESR and DAS28-CRP). CONCLUSION: Our results show that the candidates for TNF inhibitors will be enormously changed according to a change in the reimbursement criteria. To define appropriate patients to receive TNF inhibitors, a further study with regard to the impact of changes in the reimbursement criteria on the outcomes of RA patients will be required.

Role of Citrullinated Fibrinogen Peptides in the Activation of CD4 T Cells from Patients with Rheumatoid Arthritis

This study was conducted to determine whether CD4 T cell responses to citrullinated fibrinogen occur in patients with rheumatoid arthritis (RA), especially in HLA-DR4-positive subjects. Whole peripheral blood mononuclear cells (PBMCs) of RA patients and control subjects were stimulated with citrullinated fibrinogen peptides, and T-cell production of proliferation and proinflammatory cytokines, such as interferon-gamma(IFN-gamma) and interleukin-17A (IL-17A), were measured. In addition, CD4 T cells from RA patients were stimulated with the citrullinated fibrinogen peptide, Fib-alpha R84Cit, identified as a DRB1*0401-restricted T cell epitope in HLA-DR4 transgenic mice, and the degree of T cell activation was examined similarly. No proliferative responses to the citrullinated fibrinogen peptides were observed in whole PBMCs or CD4 T cells from RA patients. Furthermore, no increased production of IFN-gamma or IL-17A was found in whole PBMCs or CD4 T cells stimulated with the citrullinated fibrinogen peptides, although these cells responded to recall antigen, a mixture of tetanus toxoid, purified protein derivative (PPD) from Mycobacterium tuberculosis, and Candida albicans. The results of this study indicate that anti-citrulline immunity in RA patients may be mediated by fibrinogen because there is no evidence of CD4 T cell-mediated immune responses to citrullinated fibrinogen peptides.

Animal Models in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disorder affected by multiple genetic, hormonal and environmental factors, which makes it impossible to identify the exact cause of this ailment by only investigating SLE patients, who are genetically heterogeneous, and live in various environments. Therefore, the study of mouse models of lupus has provided valuable clues to help identify, and to validate, novel molecular pathways and targets implicated in the pathogenesis of the disease. While there is no perfect model to reflect all the disease phenotypes observed in human patients, disease subsets are represented in various animal models, which allows modulation of a particular pathophysiological pathway, resulting in the possibility of dissecting its specific contribution to disease development. Spontaneous mouse models of lupus have led to identification of numerous susceptibility loci, from which several candidate genes have been found, while induced models of lupus have provided insight into the role of environmental factors, as well as a better understanding of the cellular mechanisms by which SLE develops. Animal models also allow us to screen and evaluate potential preventive and therapeutic agents. Correlation of specific pathways in animal models to subsets of human disease offers the unique possibility of more accurate preclinical predictions of efficacy for single or combinatorial therapeutic approaches in the clinic. Here, we introduce various animal models of SLE, and review current data focused on genetic factors that are associated with susceptibility or phenotypes of lupus, leading into the present understanding of the genetic basis in lupus pathogenesis.

Gene Expression Profile of T-cell Receptors in the Synovium, Peripheral Blood, and Thymus during the Initial Phase of Collagen-induced Arthritis

BACKGROUND: Current management strategies attempt to diagnose rheumatoid arthritis (RA) at an early stage. Transcription profiling is applied in the search for biomarkers for detecting early-stage disease. Even though gene profiling has been reported using several animal models of RA, most studies were performed after the development of active arthritis, and conducted only on the peripheral blood and joint. Therefore, we investigated gene expression during the initial phase of collagen-induced arthritis (CIA) before the arthritic features developed in the thymus in addition to the peripheral blood and synovium. METHODS: For gene expression analysis using cDNA microarray technology, samples of thymus, blood, and synovium were collected from CIA, rats immunized only with type II collagen (Cll), rats immunized only with adjuvant, and unimmunized rats on days 4 and 9 after the first immunization. Arrays were scanned with an Illumina bead array. RESULTS: Of the 21,910 genes in the array, 1,243 genes were differentially expressed at least 2-fold change in various organs of CIA compared to controls. Among the 1,243 genes, 8 encode T-cell receptors (TCRs), including CD3zeta, CD3delta, CD3epsilon, CD8alpha, and CD8beta genes, which were down-regulated in CIA. The synovium was the organ in which the genes were differentially expressed between CIA and control group, and no difference were found in the thymus and blood. Further, we determined that the differential expression was affected by adjuvant more than Cll. The differential expression of genes as revealed by real-time RT-PCR, was in agreement with the microarray data. CONCLUSION: This study provides evidence that the genes encoding TCRs including CD3zeta, CD3delta, CD3epsilon, CD8alpha, and CD8beta genes were down-regulated during the initial phase of CIA in the synovium of CIA. In addition, adjuvant played a greater role in the down-regulation of the CD3 complex compared to CII. Therefore, the down-regulation of TCR gene expression occurred dominantly by adjuvant could be involved in the pathogenesis of the early stage at CIA.

Gene Expression Profile of T-cell Receptors in the Synovium, Peripheral Blood, and Thymus during the Initial Phase of Collagen-induced Arthritis

BACKGROUND: Current management strategies attempt to diagnose rheumatoid arthritis (RA) at an early stage. Transcription profiling is applied in the search for biomarkers for detecting early-stage disease. Even though gene profiling has been reported using several animal models of RA, most studies were performed after the development of active arthritis, and conducted only on the peripheral blood and joint. Therefore, we investigated gene expression during the initial phase of collagen-induced arthritis (CIA) before the arthritic features developed in the thymus in addition to the peripheral blood and synovium. METHODS: For gene expression analysis using cDNA microarray technology, samples of thymus, blood, and synovium were collected from CIA, rats immunized only with type II collagen (Cll), rats immunized only with adjuvant, and unimmunized rats on days 4 and 9 after the first immunization. Arrays were scanned with an Illumina bead array. RESULTS: Of the 21,910 genes in the array, 1,243 genes were differentially expressed at least 2-fold change in various organs of CIA compared to controls. Among the 1,243 genes, 8 encode T-cell receptors (TCRs), including CD3zeta, CD3delta, CD3epsilon, CD8alpha, and CD8beta genes, which were down-regulated in CIA. The synovium was the organ in which the genes were differentially expressed between CIA and control group, and no difference were found in the thymus and blood. Further, we determined that the differential expression was affected by adjuvant more than Cll. The differential expression of genes as revealed by real-time RT-PCR, was in agreement with the microarray data. CONCLUSION: This study provides evidence that the genes encoding TCRs including CD3zeta, CD3delta, CD3epsilon, CD8alpha, and CD8beta genes were down-regulated during the initial phase of CIA in the synovium of CIA. In addition, adjuvant played a greater role in the down-regulation of the CD3 complex compared to CII. Therefore, the down-regulation of TCR gene expression occurred dominantly by adjuvant could be involved in the pathogenesis of the early stage at CIA.

Pill induced esophagitis / 대한내과학회지

No abstract available.

Successful Treatment of Interstitial Pneumonitis Induced by Leflunomide / 대한류마티스학회지

Leflunomide is a disease-modifying antirheumatic drug that has been available in Korea since 2003. Leflunomide induced interstitial pneumonitis has been reported as an adverse effect in other countries but not in Korea. A 57-year-old woman was treated with leflunomide since she had been resistant to methotrexate, hydroxychloroquine and sulfasalazine. She developed high fever, dyspnea, and non-productive cough 3 months after the administration of leflunomide. She was diagnosed leflunomide-induced interstitial pneumonitis based on history, physical, laboratory, radiologic and pathologic findings. The patient was treated by prednisolone 1 mg/kg/day with cholestyramine 24 g/day, resulting in dramatic improvement. Here we report a case of leflunomide induced pneumonitis treated successfully with high dose steroid.

Association of FOXJ1 polymorphisms with systemic lupus erythematosus and rheumatoid arthritis in Korean population

The forkhead-box J1 (FOXJ1) transcription factor could suppress a spontaneous activation of T cells and B cells through an induction of IkappaBbeta that results in repression of NF-kappaB activity. In Foxj1 deficiency mice, systemic autoimmune inflammation is quite common symptom. Therefore, deregulated Foxj1 is supposed to be associated with autoimmune diseases and/or other inflammatory diseases. Previously, we identified that polymorphisms of human FOXJ1 gene (g.-460C>T, g.1805G>T and g.3375G>C) are associated with allergic rhinitis in a Korean population. In present study, we compared the genotype and allele frequencies of these SNPs between healthy controls and systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) patients. We also investigated the relationships between each genotype and the expression levels of anti-nuclear antibodies in SLE patients, and rheumatoid factor and anti-cyclic citrullinated peptide in RA patients. The frequencies of haplotypes constructed by these FOXJ1 SNPs were compared between controls and SLE (or RA) patients. The results of genotype and allele analysis showed that the prevalence of polymorphism g.3375G>C was associated with the susceptibility of SLE (P = 0.0072 and 0.0042, respectively). But no significant association was found with RA. In the haplotype analysis, however, the main CGG showed a weak association between controls and RA patients (P = 0.048).

A Case of Idiopathic Thrombocytopenic Purpura in a Patient with Behcet's Disease / 대한류마티스학회지

In Behcet's disease, thrombocytopenia has rarely been reported in association with the hemolytic uremic syndrome, thrombotic thrombocytopenic purpura or in association with cyclosporine or chlorambucil in the treatment of ocular inflammatory disease and meningoencephalitis. In this paper we report a case of thrombocytopenia in a 33-year-old female with Behcet's disease who has taken no medications for three years. After history taking, physical examination, routine laboratory and bone marrow examination, we diagnosed her case as idiopathic thrombocytopenic purpura (ITP). She recovered with high dose steroid treatment. To our knowledge, this is the first report having ITP in a patient with Behcet's disease.

Role of T lymphocyte in the pathogenesis of rheumatoid arthritis / 한양의대학술지

PURPOSE OF REVIEW: Rheumatoid arthritis (RA) is characterized by a chronic T-cell response that has escaped normal control mechanisms. This review summarizes recent insights in pathways that are functional in RA and that favor continuous and pathogenic T-cell activation. RECENT FINDINGS: T-cell activation is ultimately determined by positive signals from costimulatory molecules and negative signals from regulatory T cells. Blockade of the classic costimulatory pathway, CD28-CD80 or CD86, is beneficial in RA. Additional pathways that predominantly control the activation of memory and effector T cells are functionally important in synovial inflammation. Some of these costimulatory molecules(such as stimulatory killer cell immunoglobulin-like receptors and NKG2D) appear to be relatively specific for RA and not to play a role in normal immune responses. In addition to this predominance of positive signals, age-disproportionate decline in thymic activity in RA may lead to a diminution of regulatory T cells and loss of their negative signals. SUMMARY: The successful treatment trial of RA with CTLA-4Ig clearly documents the importance of T-cell costimulation in RA disease activity. Novel costimulatory pathways may be of even greater significance than CD28 in RA and may represent promising new therapeutic targets. The finding of reduced thymic activity in RA is exciting and will stimulate further studies of T-cell homeostasis and the function of regulatory cells.

Diagnostic Performances of Anti-Cyclic Citrullinated Peptides Antibody and Antifilaggrin Antibody in Korean Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease of unknown etiology. We studied the diagnostic performances of anti-cyclic citrullinated peptides antibody (anti-CCP) assay and recombinant anti-citrullinated filaggrin antibody (AFA) assay by enzyme linked immunosorbent assay (ELISA) in patients with RA in Korea. Diagnostic performances of the anti-CCP assay and AFA assay were compared with that of rheumatoid factor (RF) latex fixation test. RF, anti-CCP, and AFA assays were performed in 324 RA patients, 251 control patients, and 286 healthy subjects. The optimal cut off values of each assay were determined at the maximal point of area under the curve by receiver-operator characteristics (ROC) curve. Sensitivity (72.8%) and specificity (92.0%) of anti-CCP were better than those of AFA (70.3%, 70.5%), respectively. The diagnostic performance of RF showed a sensitivity of 80.6% and a specificity of 78.5%. Anti-CCP and AFA showed positivity in 23.8% and 17.3% of seronegative RA patients, respectively. In conclusion, we consider that anti-CCP could be very useful serological assay for the diagnosis of RA, because anti-CCP revealed higher diagnostic specificity than RF and AFA at the optimal cut off values and could be performed by easy, convenient ELISA method.

Expression of Receptor Activator of NF-kB Ligand (RANKL) and Formation of Osteoclast in Cultured Synovial Fibroblasts / 대한류마티스학회지

OBJECTIVE: A number of soluble factors,which play important role in the pathophysiology of rheumatoid synovitis are also known to be involved in osteoclast differentiation and activation through RANKL (Receptor activator of NF-kB ligand). To investigate the importance of RANKL in the pathogenesis of bone erosion in rheumatoid arthritis (RA) patients, we analyzed the expression of RANKL and Osteoprotegerin (OPG) and examined the formation of osteoclasts in rheumatoid synovial fibroblasts under the influence of various osteotropic factors. METHODS: Primary culture synoviocytes or fibroblast-like synoviocytes isolated from synovial tissues of 8 RA patients were cultured and treated with IL-1beta (2 ng/ml), TNF-alpha (2 ng/ml), INF-gamma(1000 micro/ml), IL-15 (10 ng/ml), IL-12 (10 ng/ml), dexamethasone (10(-9) M), PMA (10 ng/ml) or 1,25 (OH)2D3 (10(-9) M) for 18 hours. Expression RANKL or OPG mRNA was measured by semiquantitative RT-PCR within linear amplification condition. TRAP (+) MNC (tartrate resistant acid phosphatase-positive multinucleated cell) formation was induced from primary culture synoviocytes or in coculture system of synovial fibroblasts with PBMCs in the presence of M-CSF and 1,25 (OH)2D3. RESULTS: 1. The intensity of base-line expression was different from patient to patient. Primary culture synoviocytes and synovial fibroblasts express RANKL and OPG mRNA with decreasing intensity when they are passaged. 2. Expresssion of RANKL mRNA was significantly increased by 1,25 (OH)2D3 and IL-1beta (158.8+/-21% and 197.2+/-17% of controls, p<0.05 and p<0.005, respectively), while decreased significantly by dexamethasone (25.6+/-4.6% of controls, p<0.005). Expression of RANKL mRNA was significantly increased by IL-1beta and decreased by dexamethasone, in a dose- and time-dependant manner. 3. TRAP (+) MNCs are formed from primary culture synoviocytes or in coculture system of synovial fibroblasts and PBMC in the presence of M-CSF and 1,25 (OH)2D3. Dexamethasone clearly inhibited TRAP (+) MNCs formation from synovial cells. CONCLUSION: The regulatory mechanism for the expression of RANKL or OPG in rheumatoid synoviocytes might be different from that in bone marrow cells. Modulating the expression of these molecules could have potential therapeutic implication targeting bone destruction in RA.

Diagnostic Performance of the Antifilaggrin Antibody in Rheumatoid Arthritis / 임상검사와정도관리

BACKGROUNDS: Rheumatoid factor (RF) is common serological marker for the diagnosis of rheumatoid arthritis (RA), but its sensitivity and specificity are not satisfactory for the diagnosis of RA. Therefore, we investigated the diagnostic performance of a new antifilaggrin antibody test by enzyme linked immunosorbent assay (ELISA) in RA. METHODS: Recombinant human filaggrin was deiminated in vitro by peptidylarginine deiminase and used as the coating antigen for ELISA. We performed the RF and the antifilaggrin antibody for 324 RA patients, 251 non-RA patients (rheumatic diseases other than RA), and 286 normal individuals and evaluated the sensitivities and specificities of RF and antifilaggrin antibody. Optimal cut off values were calculated as mean+2SD in 95% confidence interval except 3SD for 286 normal individuals. Optimal cut off values of antifilaggrin antibody and RF were 9.6 U/ml and 12 U/ml, respectively. RESULTS: The sensitivities and specificities of antifilaggrin antibody were 44.8% and 89.2% at optimal cut off values. The sensitivity and specificity of RF were 75.0% and 83.3%. Combination of "antifilaggrin antibody and RF" showed significantly high specificity of 95.2% and that of "antifilaggrin antibody or RF" showed slightly high sensitivity of 79.3% at optimal cut off values. Antifilaggrin antibody was positive in 17.3% among 81 sero-negative RA patients. CONCLUSION: We considered that antifilaggrin antibody could be used a supplementary test of RF for the diagnosis of RA, because "antifilaggrin antibody and RF" had higher diagnostic specificity than RF alone and antifilaggrin antibody test was easy, convenient ELISA method in performance.

Diagnostic Performance of the Anti-Cyclic Citrullinated Peptide Antibodies in Rheumatoid Arthritis / 대한진단검사의학회지

BACKGROUND: The Rheumatoid Factor (RF) is the only serological marker in the diagnosis of rheumatoid arthritis (RA), but its sensitivity and specificity are not satisfactory for the diagnosis of RA. Therefore, we investigated the diagnostic performance of a new anti-cyclic citrullinated peptide antibodies test (anti-CCP) by the enzyme-linked immunosorbent assay (ELISA) in RA. METHODS: A cyclic peptide variant that contains citrulline was used as an antigenic substrate in ELISA. We performed the RF and anti-CCP in 324 RA patients, 251 non-RA patients (rheumatic diseases other than RA), and 286 normal individuals. Diagnostic performances such as sensitivity and specificity were evaluated by the receiver-operator characteristics (ROC) curve at optimal cut-off values. The optimal cut-off values were determined at the maximal point of the area under the curve. RESULTS: The sensitivity and specificity of anti-CCP were 72.8% and 92% at 3.8 U/mL. The sensitivity and specificity of RF were 80.6% and 78.5% at 9 U/mL. The sensitivity and specificity of anti-CCP and RF were 67%, 95.2% and 63.3%, 90% at 8.4 U/mL, 20 U/mL, respectively. A combination of anti-CCP with RF increased the sensitivity and specificity to 79.3%, 96.4%, respectively. Anti-CCP was positive in 23.8% among 63 sero-negative RA patients. CONCLUSIONS: We considered that the anti-CCP might be useful as another new serological marker for the diagnosis of a RA combination with RF, or not, because the anti-CCP has a higher diagnostic specificity than the RF and was an easy, convenient ELISA method in performance.

Acute leukemian in patients with juvenile rheumatoid arthritis displaysing multiply osteolytic lesions and compression fracture / 대한내과학회지

No abstract available.