Osteoclasts are a major component of bone metabolism in physiologic condition and in rheumatoid arthritis (RA). RA is a chronic, autoimmune, inflammatory disease primarily affecting the joints. Joint inflammation leads to cartilage and bone destruction by osteoclast activation. This osteoclast activation leads to typical RA symptoms and is the therapeutic target. Several kinds of drugs are used for preventing bone loss by osteoclasts in RA patients. However, the bone destructive action of osteoclasts is not the only mechanism in RA pathogenesis. Recent research suggests that the osteoclasts regulate hematopoietic stem cell niches and invoke immune responses in bone. Osteoclasts are derived from bone marrow hematopoietic stem cells, and maintain the hematopoietic stem cell niches contract with osteoblasts. Osteoclasts secret several cytokines to regulate inflammation and T cell differentiation, and present antigen to T cells via major histocompatibility complex class I and class II molecules. Osteoclast concepts in both origins and functions are under major reconsideration and research. In this review, we will discuss these new insights.
Arthritis, Rheumatoid* ; Bone Marrow ; Cartilage ; Cell Differentiation ; Cytokines ; Hematopoietic Stem Cells ; Humans ; Inflammation ; Joints ; Major Histocompatibility Complex ; Metabolism ; Osteoblasts ; Osteoclasts* ; RANK Ligand ; T-Lymphocytes

No abstract available.
Arthritis, Rheumatoid* ; Lung Diseases* ; Lung*

Human immunodeficiency virus (HIV) infection is a global pandemic affecting more than 2.9 million people. Aside from opportunistic infections and malignancies, it involves multiple organs, resulting in many complications, and frequently shows various rheumatic manifestations. With improving survival of patients due to the development of highly active anti-retroviral therapy, the number of HIV-infected patients with rheumatic complications is certain to increase. However, reports on HIV induced rheumatic manifestations in Korean patients are limited. On the other hand, spondyloarthropathy is the most common form of inflammatory arthropathy in HIV associated rheumatic manifestations and is frequently accompanied by peripheral arthritis and enthesitis, while axial skeletal involvement is a rare presentation. Herein we report on a 46-year-old man with HIV infection presenting with an axial spondyloarthropathy who was treated successfully with nonsteroidal anti-inflammatory drug, sulfasalazine, and low dose steroid.
Arthritis ; Hand ; HIV Infections ; HIV* ; Humans ; Humans* ; Middle Aged ; Opportunistic Infections ; Pandemics ; Rheumatic Diseases ; Spondylarthropathies* ; Sulfasalazine

Rheumatoid arthritis (RA) mainly affects polyarticular joints and is characterized by inflammation of the synovial membrane leading to joint destruction. We report on an unusual case of RA presenting as an intra-articular mass invading bone of the wrist joint in a patient with chronic monoarthritis. A 43-year-old man presented with left wrist joint pain and swelling lasting several years. A plain radiograph showed a non-specific osteolytic lesion in the distal ulna but a magnetic resonance image demonstrated an intra-articular irregular mass-like lesion with eccentric bone erosion the distal radioulnar joint. Synovial biopsy detected hyperplasia of the synovial lining cell layer and finger-like protrusions of inflamed and edematous fibrovascular stroma containing dense inflammatory infiltrates, mainly plasma cells, B cells, and CD4+ T cells. Rheumatoid factor and anti-citrullinated protein antibody were highly positive. The patient was diagnosed with RA and treated with disease-modifying anti-rheumatic drugs, showing a good response on further follow-up.
Adult ; Antirheumatic Agents ; Arthritis, Rheumatoid* ; B-Lymphocytes ; Biopsy ; Follow-Up Studies ; Humans ; Hyperplasia ; Inflammation ; Joints ; Plasma Cells ; Rheumatoid Factor ; Synovial Membrane ; T-Lymphocytes ; Ulna ; Wrist Joint* ; Wrist*

OBJECTIVE: Granulomatosis with polyangiitis (GPA), formally known as Wegener's granulomatosis, is a systemic vasculitis with necrotizing granulomatous inflammation. As treatment directed against tumor necrosis factor (TNF)-alpha failed in GPA, we investigated whether "TNF-alpha signature" (i.e. gene expression profile of TNF-alpha activation) was present in peripheral blood mononuclear cells (PBMCs) of patients with GPA. METHODS: Gene expression profiling was performed using total RNA from PBMCs of 41 patients with GPA and 23 healthy control subjects using the Illumina microarray technique. Gene set enrichment analysis (GSEA) was performed to detect the presence of TNF-alpha signature using the curated list C2-V3.0 by the Broad Institute. False discovery rate<0.05 was considered statistically significant. RESULTS: GSEA did not show significant enrichment of any TNF-alpha associated gene sets in GPA. Expression levels of genes up-regulated by TNF-alpha did not differ between healthy control subjects, patients in remission (Birmingham Vasculitis Activity Score [BVAS]=0), and those with active disease (BVAS> or =1). In addition, an unsupervised hierarchical clustering of those genes failed to cluster the samples into healthy control subjects and GPA in remission or with active disease. B cell activation signature was enriched in GPA patients. CONCLUSION: Absence of a TNF-alpha signature in PBMCs may suggest that TNF-alpha plays a less important role in the pathogenesis of GPA than previously accepted.
Gene Expression ; Gene Expression Profiling ; Humans ; Inflammation ; RNA ; Systemic Vasculitis ; Transcriptome ; Tumor Necrosis Factor-alpha* ; Vasculitis ; Wegener Granulomatosis

OBJECTIVE: The purpose of this study is to evaluate the outcome of uveitis in ankylosing spondylitis (AS) during tumor necrosis factor (TNF)-inhibiting therapy and to compare the incidence rate of uveitis in infliximab, adalimumab, and etanercept. METHODS: A retrospective evaluation was performed in AS patients who had started TNF-inhibiting therapy from June 2003 to June 2011. The clinical characteristics of patients with documented uveitis were evaluated. RESULTS: Among 316 patients treated with TNF inhibitor, 26 patients (8%) had experienced uveitis during TNF-inhibiting therapy. Among them, 15 patients were treated with etanercept, eight with adalimumab, and three with infliximab. The overall incidence rate of uveitis flare during therapy with TNF inhibitor was 46 per 1,000 person-years (pys) (95% confidence interval [CI], 32 to 64). The incidence rate did not differ between TNF inhibitors, with 54/1,000 pys (95% CI, 34 to 81) for etanercept, 46/1,000 pys (95% CI, 21 to 87) for adalimumab, and 22/1,000 pys (95% CI, 5 to 64) for infliximab. Fourteen patients experienced a first episode of uveitis. The overall incidence rate of new onset-uveitis after therapy with TNF inhibitor was 19 per 1,000 pys (95% CI, 10 to 31). The incidence rate for etanercept was 24/1,000 pys (95% CI, 12 to 45); adalimumab, 15/1,000 pys (95% CI, 3 to 45); and infliximab, 7/1,000 pys (95% CI, 0 to 40). There was no statistical difference in the incidence of uveitis flare or the cumulative uveitis-free rate among the three TNF inhibitors. CONCLUSION: The relative rate of uveitis, including the first episode, was determined using the TNF inhibitor. However, there was no difference in the incidence rate of uveitis among the three TNF inhibitors.
Humans ; Incidence* ; Korea* ; Retrospective Studies ; Spondylitis, Ankylosing* ; Tumor Necrosis Factor-alpha* ; Uveitis* ; Adalimumab ; Infliximab ; Etanercept

Reactivation of hepatitis B virus (HBV) is not infrequently reported in patients with rheumatologic diseases treated with biologic disease modify anti-rheumatic drugs (DMARDs) such as a tumor necrosis factor-alpha inhibitor or a B cell depleting molecule. HBV reactivation is reported not only in patients with chronic hepatitis B but also in cases with resolved HBV where HBsAg is negative and anti-HBc positive. Studies suggest that with treatment using biologic DMARDs, the risk of HBV reactivation increases when HBsAg is positive independent of HBV DNA replication status, and in those with anti-HBc positive and serum HBV DNA positive. Therefore, testing for HBsAg as well as anti-HBc is important before initiating treatment with a biologic DMARD. In addition, evaluation of serum HBV DNA may be required when either HBsAg or anti-HBc turns out to be positive. Although series of reports suggest that prophylactic antiviral therapy in patients with higher risk of HBV reactivation would diminish morbidity and mortality from hepatic cause, solid guidelines pertaining to when to initiate and terminate HBV antiviral therapy and which agent should be used should be provided in the future.
Antirheumatic Agents* ; DNA ; DNA Replication ; Hepatitis B Surface Antigens ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis B, Chronic ; Hepatitis* ; Humans ; Mass Screening* ; Mortality ; Tumor Necrosis Factor-alpha

Rheumatoid arthritis (RA) is a systemic inflammatory disease associated with both genetic and environmental factors. The DRB1 gene at the human leukocyte antigen (HLA) locus of chromosome 6p21.3 was the first genetic factor associated with RA to be identified in the 1980s; however, identification of causative genes other than those at the HLA locus has been challenging for geneticists because of the strong linkage disequilibrium in this locus and the non-Mendelian inheritance pattern of RA. Recent advances in high-throughput single nucleotide polymorphism genotyping technologies and bioinformatic analysis tools have facilitated the identification of positive associations of hundreds of genes with RA using family-based linkage analyses and genome wide association studies. Some of the RA associated genes at non-HLA loci are as follows: PADI4, PTPN22, STAT4, and TNFAIP3. In this paper, we describe the pathological mechanisms mediated by these genes. In addition, we review results of previous genetic studies of RA and future challenges in connecting the dots of missing heritability in the post-genome-wide association study era.
Arthritis, Rheumatoid* ; Genetics ; Genome-Wide Association Study ; Humans ; Inheritance Patterns ; Leukocytes ; Linkage Disequilibrium ; Polymorphism, Single Nucleotide

No abstract available.
Arthritis, Rheumatoid* ; Education*

No abstract available.
Female ; Humans ; Spondylitis, Ankylosing