Current Rheumatology Reviews - Volume 7, Issue 4, 2011

This has been an interesting year in rheumatology. After about 50 years, we have a drug approved for the treatment of SLE. There are several investigational molecules currently in advanced clinical trials in several conditions, and our group completed the biggest controlled trial in Myositis ever. In this issue, we take a step back to understand the mechanisms of several signaling pathways such as NF-kB, the RAS system, IL-6 Read More

During the past two decades intense research expanded our understanding of the mechanisms underlying the pathogenesis of autoimmune diseases. As a result, a new class of antirheumatic drugs, designed to target various signaling pathways abnormally activated in the immune system have been introduced into the clinic. The proliferation, differentiation and function of various cellular components of the immune Read More

Excess activation of NF-kappa B is often involved in inflammation and cancer progression. We have developed a specific NF-kappa B inhibitor dehydroxyepoxyquinomicin (DHMEQ). It binds to the specific cysteine residue of Rel family proteins. DHMEQ inhibited cytokine secretions and osteoclastogenesis in cultured macrophages. It inhibited various animal models of inflammation and cancer. Especially, it inhibited type Read More

The nuclear factor-κB (NF-κB) family of transcription factors consists of the five members; RelA, RelB, c-Rel, NF-κB1 and NF-κB2, which form homodimers or heterodimers and act via two distinct pathways known as the canonical and non-canonical pathways. A multitude of intracellular molecules participates in the positive and negative regulation of these pathways. Under physiological conditions, signaling via NF-κB play Read More

Interleukin (IL)-6 has many biological functions. It induces acute-phase reactants (CRP, SAA) and suppresses albumin. It induces hepcidin, which regulates iron recycling and absorption, causing iron-deficiency anemia. It induces synovial cells to express receptor activator of nuclear factor-κB ligand (RANKL) and secrete vascular endothelial growth factor (VEGF), leading to osteoclast differentiation and neovascularization. In mi Read More

Loss of self tolerance is the key feature of autoimmunity. The p21Ras/MAP kinase pathway plays a major role in the regulation, selection, differentiation and maturation of lymphocytes. Therefore it is conceivable that malfunctioning of this pathway due to permanent or transient signaling defects can lead to an aberrant clonal selection at the thymus or loss of anergy in the periphery. Multiple disease dependent si Read More

Treatment of rheumatoid arthritis (RA) with biologic agents targeting inflammatory cytokines and cell surface molecules such as Tumor necrosis factor (TNF), Interleukin-6 (IL-6) and CTLA-4 has become a major focus in the field. Biologic agents are generally more effective than traditional disease-modifying antirheumatic drugs (DMARDs) when combined with MTX. However, not only about 30% of patients respond poorly to Read More

The antiphospholipid syndrome is characterized by the presence of arterial or venous thrombosis or recurrent miscarriages in a patient with positive laboratory tests for antiphospholipid antibodies (anticardiolipin antibodies and/or lupus anticoagulant and/or anti-beta2-glycoprotein I). Despite the strong association between antiphospholipid antibodies and thrombosis and obstetric morbidity, their pathogenic role in the Read More

The cause of ankylosing spondylitis (AS) was investigated through 11 Karl Popper sequences. “Popper sequences&rdquo provide a powerful method of investigating a scientific problem. A “Popper sequence” consists of a “problem”, “tentative theory”, “error elimination” which then leads to a “new fact”. The 11 “Popper sequences” establish that: (1) HLA-B27 lymphocytes injected into a rabbit evoke antibodies against Klebsiella Read More