This study was performed to define the clinical spectrum and disease manifestations of ankylosing spondylitis (AS) in a referral hospital setting. We identified the differences in clinical manifestations according to the sex, the age at onset, the presence of peripheral arthritis and the presence of HLA B27. A total 412 patients (357 males, 55 females) were recruited. Eighty-seven percent were men and 155 out of 412 patients (35%) were juvenile-onset. HLA B27 was detected in 385 patients (93%). Peripheral joint involvement was noted in 287 of total AS cases (juvenile- onset ankylosing spondylitis (JOAS), 82%; adult-onset ankylosing spondylitis (AOAS), 61%), and was more common than those reported in other studies. A greater portion of patients with JOAS had peripheral arthritis and peripheral enthesitis than the patients with AOAS. The patients with peripheral arthritis showed a younger age at onset and an increased tendency of having enthesitis and trauma history. The natural history of Korean AS appears largely similar to those seen in Europe and North America, except a few differences. JOAS was quite common and AS was about nine times more common in men than in women. In addition, the HLA B27 antigen frequency was 93%, which is higher than those reported in other studies.
Adolescent ; Adult ; Age of Onset ; Arthritis/*etiology/immunology ; Female ; HLA-B27 Antigen ; Humans ; Korea ; Male ; Sex Characteristics ; Spondylitis, Ankylosing/*complications/immunology

Primary thymic marginal zone B-cell lymphoma (MZBL) of mucosa-associated lymphoid tissue (MALT)-type is a very rare disease with distinct clinicopathologic features. I herein report a rare case of primary thymic MZBL of MALT-type arising in the thymus in a patient with Sjogren's syndrome and rheumatoid arthritis. A mediastinal mass was detected by computerized tomography in a 43-yr-old Korean woman with a history of Sjogren's syndrome and rheumatoid arthritis and the thymus was resected through median sternotomy. The solid and nodular tumor (7x6x3cm) was confined in the thymus. Histologically, the lymphoid infiltrate comprised monotonous centrocyte-like cells with monocytoid cells, small lymphocytes, and plasma cells. Prominent lymphoepithelial lesions were formed by centrocyte-like cells infiltrating the Hassall's corpuscles. Immunohistochemically, the tumor cells were positive for CD20, CD79a, and bcl-2 and negative for CD3, CD5, CD10, CD23, and bcl-6. IgA and kappa light chain restriction were also found in plasma cells in the tumor. Sjogren's syndrome and rheumatoid arthritis are known to be associated with MALT lymphoma and were considered to play an important role in the development of malignant lymphoma in this patient.
Adult ; Arthritis, Rheumatoid/*complications/immunology ; B-Lymphocytes/metabolism ; Female ; Human ; Lymphoma, Mucosa-Associated Lymphoid Tissue/diagnosis/*etiology/immunology ; Sjogren's Syndrome/*complications/immunology ; Thymus Neoplasms/immunology/*pathology ; Tumor Markers, Biological

Adalimumab ; adverse effects ; therapeutic use ; Antirheumatic Agents ; adverse effects ; therapeutic use ; Arthritis, Rheumatoid ; drug therapy ; immunology ; Asian Continental Ancestry Group ; Autoantibodies ; immunology ; Female ; Humans ; Immunoglobulin A ; immunology ; Middle Aged ; Nephritis ; etiology ; immunology

Inhibitors of tumor necrosis factor-alpha (TNF-alpha) have been approved for treating rheumatoid arthritis. As one of the biological response modifiers, etanercept has also been used in the treatment of psoriatic arthritis and inflammatory bowel disease. While etanercept is effective, certain infectious complications, such as tuberculosis, fungus, and cytomegalovirus, have been reported. We report the first Korean case of adenoviral pneumonia in a 55-year-old female who developed disseminated adenoviral infection following etanercept treatment, which resolved after anti-TNF-alpha discontinuation.
Risk Factors ; Recombinant Fusion Proteins/immunology ; Receptors, Tumor Necrosis Factor/immunology ; Middle Aged ; Immunoglobulin G/*adverse effects/immunology ; Immunocompromised Host/drug effects ; Humans ; Female ; Arthritis, Rheumatoid/*drug therapy ; Antirheumatic Agents/*adverse effects/immunology ; Antibodies, Monoclonal/*adverse effects/immunology ; Adenovirus Infections, Human/*etiology/immunology

BACKGROUNDMacrophage-inducible C-type lectin (MINCLE) is an important member of C-type lectin superfamily, which has been shown evidence for susceptibility to arthritis in animal models. We aimed to investigate the possible association of MINCLE with rheumatoid arthritis (RA) susceptibility in Chinese Han population.

METHODSHaplotypes from HapMap database (Chinese Han Beijing, CHB) were used to select tag-single nucleotide polymorphism (SNP) (r(2) = 0.8) residing in MINCLE gene. A total of 563 patients with RA and 404 healthy controls were TagMan genotyped for SNP rs10841845. Association analyses were performed on the whole data set and on RA subsets based on gender difference and the status of anti-cyclic citrullinated peptide (anti-CCP) antibody in RA patients. Association statistics were calculated by age and sex adjusted logistic regression.

RESULTSOverall, MINCLE SNP rs10841845 was not associated with susceptibility to RA. However, following anti-CCP stratification, rs10841845 GG genotypes conferred a significantly protective effects against anti-CCP-positive RA (OR 0.65, 95%CI 0.430 - 0.995, P = 0.048). Following gender stratification, SNP rs10841845 G allele appeared to insert its RA protective effect only in male patients, both at allele level (G vs. A OR 0.66, 95%CI 0.46 - 0.93, P = 0.018) and at genotype level (GG vs. AA+AG, OR 0.429, 95%CI 0.20 - 0.95, P = 0.036). Notably, the male RA protective effect of rs10841845 G allele was only seen in anti-CCP-positive RA (G vs. A: OR 0.64, 95%CI 0.43 - 0.96, P = 0.029; GG vs. AA+AG: OR 0.375, 95%CI 0.14 - 0.94, P = 0.038). Furthermore, we observed a significant reduction of Disease Activity Score (DAS) 28 score (3.91 ± 0.70 vs. 5.66 ± 0.31, P = 0.022) and serum C-reactive protein levels (31.64 ± 24.13 vs. 91.80 ± 12.02, P = 0.012) in male anti-CCP-positive RA patients carrying rs10841845 GG genotype, compared with patients carrying AA+AG genotypes.

CONCLUSIONSOur study provides the evidence for a gender specific association between MINCLE rs10841845 and RA susceptibility. The SNP rs10841845 G allele appears to have protective effect against anti-CCP-positive RA and confer reduced RA activity in men.

Aged ; Antibodies ; blood ; Arthritis, Rheumatoid ; etiology ; genetics ; immunology ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Lectins, C-Type ; genetics ; Male ; Middle Aged ; Peptides, Cyclic ; immunology ; Polymorphism, Single Nucleotide ; Receptors, Immunologic ; genetics

OBJECTIVETo investigate the impact of rheumatoid arthritis (RA)-associated HLA-DRbeta1 * 0401, * 0402, * 0403, * 0404 and * 0101 subtypes on the protein kinase A (PKA) signaling pathway.

METHODSAdenylate cyclase (AC), cAMP and PKA activity in transfectants expressing RA-associated HLA-DRbeta1 subtypes and their mutants were detected.

RESULTSCompared to HLA-DRbeta1 * 0402 transfectants, the RA-associated HLA-DRbeta1 * 0401, * 0404 and * 0101 transfectants produced significantly lower levels of AC, cAMP and PKA.

CONCLUSIONRA-associated HLA-DRbeta1 molecules are involved in the pathogenesis of RA through down-regulation of the PKA signaling pathway.

Adenylyl Cyclases ; analysis ; Arthritis, Rheumatoid ; etiology ; genetics ; immunology ; Cyclic AMP ; analysis ; genetics ; Cyclic AMP-Dependent Protein Kinases ; physiology ; Down-Regulation ; HLA-DR Antigens ; analysis ; genetics ; Immunophenotyping ; In Vitro Techniques ; Signal Transduction

OBJECTIVETo investigate the expression of discoidin domain receptor 2 (DDR2) of fibroblast-like synovial cells in improved adjuvant-induced animal (AIA) model for rheumatoid arthritis (RA) and to provide evidence for DDR2's antagonist use clinically.

METHODSAIA was modified by administrating 0.1 mL of complete Freund's adjuvant (CFA, mixed with 5 mg Bacillus Calmette-Guerin vaccine/mL) into rats' right hind paws and 0.125 mL tumor necrosis factor-alpha (2 U/mL) into right ankles and subpatellar fatty tissue. The expression of DDR2 in fibroblast-like synovial cells was assessed using immunohistochemistry, immunofluorescence histochemistry, and in situ hybridization methods. Levels of anti-collagen II antibody were measured using enzyme-linked immunosorbent assay.

RESULTSGiven the terms mentioned above, we found a more practical rat model, apparently decreasing immunization time (average 3-5 days). DDR2 can be detected upon the 15th day of immunization; expression gradually increased with time going on, and reaching a peak 35 days after immunization before gradually decreasing. Serum anti-collagen II antibody showed similar expression patterns as DDR2, but reached peak later than DDR2, about 40 days after immunization.

CONCLUSIONRegular expression of DDR2 in animal models infers its important role in the pathological process of RA.

Animals ; Antibodies ; blood ; Arthritis, Experimental ; etiology ; metabolism ; Arthritis, Rheumatoid ; chemically induced ; metabolism ; BCG Vaccine ; Collagen Type II ; immunology ; Discoidin Domain Receptors ; Female ; Fibroblasts ; drug effects ; metabolism ; pathology ; Freund's Adjuvant ; Rats ; Rats, Sprague-Dawley ; Receptor Protein-Tyrosine Kinases ; metabolism ; Receptors, Mitogen ; metabolism ; Synovial Fluid ; cytology ; metabolism

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