Rapid detection of S. mutans surface antigen I/II using a sensitive monoclonal anti-Ag I/II antibody by ELISA.

The cell-surface protein antigen I/II (Ag I/II) is expressed in oral streptococci, which are known as the causative agent of a number of diseases including dental caries, endocarditis, gingivitis, and periodontal disease. Consequently, monoclonal antibodies (MAb) capable of recognizing the streptococcal Ag I/II protein could be a useful tool for the diagnosis and cure of these diseases. In this study, a previously generated monoclonal anti-Ag I/II antibody, ckAg I/II, was used to detect a small amount of Streptococcus mutans (S. mutans) surface antigen Ag I/II. The ckAg I/II was proved to be very sensitive and able to detect as little as 1 ng of recombinant Ag I/II protein within 5 min and Ag I/II in saliva within 10 min, as well as native Ag I/II in 20 µL of culture supernatant by ELISA. These results suggest that ckAg I/II can be used as a fast and efficient diagnostic tool to detect Ag I/II.

Risk factors of severe infections in patients with rheumatoid arthritis treated with leflunomide.

OBJECTIVES: To determine the risk of severe infection requiring or complicating hospitalization associated with leflunomide therapy in patients with rheumatoid arthritis (RA). METHODS: We performed a retrospective study of RA patients who were prescribed leflunomide between 2004 and 2011. Background clinical and laboratory features were compared between patients who suffered severe leflunomide-associated infections and those who did not. RESULTS: Since January 2005, 401 RA patients have started on leflunomide. Among those, 33 (8.2%) developed severe infections: pneumonia, oral candidiasis, pyelonephritis, pulmonary tuberculosis, cellulitis, disseminated herpes zoster, tonsillitis, and pulmonary cryptococcosis. Logistic regression showed that age at entry, the presence of DM, and daily dosage of corticosteroid were associated with development of severe infections. CONCLUSIONS: These results showed that some patients with RA who were taking leflunomide developed severe infections requiring hospitalization, and that older age, DM, and a higher daily dosage of corticosteroid were risk factors associated with leflunomide-associated severe infections.

Quercetin inhibits IL-1ß-induced proliferation and production of MMPs, COX-2, and PGE2 by rheumatoid synovial fibroblast.

This study was aimed to determine the effects of quercetin on the interleukin-1ß (IL-1ß)-induced proliferation of rheumatoid synovial fibroblasts (RASFs) and production of matrix metalloproteinases (MMPs), cyclooxygenase (COX), and prostaglandin E2 (PGE2) by RASFs. The proliferation and apoptosis of RASFs was evaluated with CCK-8 reagent and flow cytometry in the presence of IL-1with CCK-8 reagquercetin. The expression of MMPs, IL-1ß enhanced the expression of MMP-1, MMP-3, tissue inhibitor of metalloproteinase (TIMP)-1, COXs, PGE2, and intracellular mitogen-activated protein kinase (MAPK) signalings including phosphorylated extracellular signal-regulated kinase (p-ERK), p-p38, phosphorylated c-Jun N-terminal kinase (p-JNK), and nuclear factor kB (NF-kB) were examined by immunoblotting or semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) in conditions as described above. Quercetin inhibits unstimulated and IL-1ß-induced proliferation of RASFs and MMP-1, 3, COX-2 messenger ribonucleic acid and protein expression, PGE2 production induced with IL-1ß. Quercetin also inhibits the phosphorylation of ERK-1/2, p38, JNK and activation of NF-kB by IL-1ed. These results indicate that quercetin inhibits synovial fibroblasts proliferation and MMPs, COX-2, and PGE2 production, which involved joint destruction in rheumatoid arthritis (RA), and suggest that it might be a new therapeutic agent for management of RA.

Successful treatment for conventional treatment-resistant dermatomyositis-associated interstitial lung disease with adalimumab.

Dermatomyositis (DM) is a systemic autoimmune disorder characterized by the inflammation of skeletal muscles and pathognomonic skin rashes, namely heliotrope rash and Gottron's papules and involvement of other organs. Interstitial lung disease (ILD) seems to be one of the most characteristic manifestations of the lung and associated with increased morbidity and mortality in patients with DM. Despite DM-associated ILD requires aggressive therapy with cytotoxic agents, the efficacy is questionable in some cases, and more effective and less toxic therapies are needed. Recently, although there have been several reports of successful treatment of refractory case of PM and DM with the TNF-α antagonists, including infliximab and etanercept, there was no enough evidence for DM-associated ILD. We described herein a patient with DM-associated ILD who had poor response to conventional therapies and successfully treated with adalimumab.

CD40 ligation of rheumatoid synovial fibroblasts regulates RANKL-mediated osteoclastogenesis: evidence of NF-kappaB-dependent, CD40-mediated bone destruction in rheumatoid arthritis.

OBJECTIVE: To determine whether CD40 ligation of rheumatoid arthritis synovial fibroblasts (RASFs) is able to induce RANKL expression and osteoclastogenesis in RASFs, and to identify its mechanism of action in patients with RA. METHODS: CD40 of RASFs was ligated with CD40 ligand (CD40L)-transfected L cells or activated T cells. The formation of osteoclasts in cocultures of CD40-ligated RASFs and T lymphocyte-depleted peripheral blood mononuclear cells was evaluated by tartrate-resistant acid phosphatase staining, detection of calcitonin receptor, and resorption pit formation assay. The expression of NF-kappaB, IkappaB alpha, ERK-1/2, phospho-ERK-1/2, p38, phospho-p38, and RANKL was examined by immunoblotting and/or semiquantitative reverse transcription-polymerase chain reaction. RESULTS: CD40 ligation of RASFs by CD40L-transfected L cells or activated T cells induced RANKL expression and enhanced osteoclastogenesis. CD40 ligation of RASFs also induced activation of ERK-1/2, p38 MAPK, and NF-kappaB and up-regulation of CD40 ligation-induced RANKL expression, whereas osteoclastogenesis was reduced in RASFs transfected with a dominant-negative mutant of IkappaB alpha or by an NF-kappaB inhibitor. However, specific inhibitors of MAPK/ERK-1/2 and p38 MAPK partially blocked the induction of RANKL expression and osteoclastogenesis. Monoclonal antibodies against interleukin-1 and tumor necrosis factor alpha partially inhibited CD40 ligation-mediated osteoclastogenesis. CONCLUSION: These results indicate that CD40 ligation of RASFs induces RANKL expression mainly via NF-kappaB activation and also results in enhanced osteoclast formation, both of which might play important roles in bone and cartilage destruction in RA. Inhibition of the CD40-CD40L interaction is a potential strategy for the prevention of bone damage in RA.

Transverse myelitis in a patient with primary antiphospholipid syndrome.

The neurological manifestations of antiphospholipid syndrome (APS) are diverse. Transverse myelitis (TM) is an uncommon, but well-known neurological complication of systemic lupus erythematosus (SLE). On the other hand, the reported cases associated with primary APS are extremely rare. To our knowledge, this is the first report of TM in a patient with primary APS in Korea. A 32-year-old male patient was admitted with the sudden onset of numbness, a tingling sensation, and weakness in both lower extremities. He had a 19 months history of external iliac and femoral arterial thromboses prior to admission. The laboratory results indicated the presence of anticardiolipin antibodies of the IgG class and lupus anticoagulant. No other autoantibodies were detected and there were no apparent clinical manifestations of SLE or multiple sclerosis. A T2-weighted magnetic resonance (MR) image showed swelling and increased intensity of the cervical and thoracic spinal cord between C6 and T7 with slight enhancement by contrast medium. After steroid pulse therapy, the patient's symptoms were gradually relieved and the abnormal findings on MR imaging disappeared.