Autoantibodies to low-density-lipoprotein-receptor-related protein 2 (LRP2) in systemic autoimmune diseases

We previously reported that autoantibodies (autoAbs) to the main epitope on CD69 reacted to its homologous amino acid sequence in low-density-lipoprotein-receptor-related protein 2 (LPR2), a multiligand receptor for protein reabsorption. In this study, we have investigated the prevalence, autoepitope distribution, and clinical significance of the autoAbs to LRP2 in patients with systemic autoimmune diseases. Using six recombinant proteins (F2–F7) for LRP2 and one for CD69, we detected autoAbs to LRP2 in sera of patients with rheumatoid arthritis (RA), systemic lupus erythematosus, Behçet's disease, systemic sclerosis, and osteoarthritis and then mapped autoepitopes by Western blotting. The autoAbs to LRP2 were detected in 87% of the patients with rheumatoid arthritis, 40% of those with systemic lupus erythematosus, 35% of those with systemic sclerosis, 15% of those with osteoarthritis, and 3% of those with Behçet's disease. Multiple epitopes on LRP2 were recognized by most of the anti-LRP2(+ )serum samples. All of the tested anti-CD69 autoAb(+ )samples reacted to LRP2-F3 containing the homologous sequence to the main epitope of CD69; however, only 38% of the anti-LRP2-F3(+ )samples reacted to CD69. Clinically, the existence of the autoAbs to LRP2-F4, -F5, and -F6 correlated with the presence of proteinuria in RA. This study revealed that LRP2 is a major autoantigen in RA. The autoAbs to LRP2 are probably produced by the antigen-driven mechanism and the autoimmunity to LRP2 may spread to include CD69. The anti-LRP2 autoAbs may play pathological roles by inhibiting the reabsorbing function of LRP2

The epigenetic function of androgen receptor in prostate cancer progression

Androgen and androgen deprivation (castration) therapies, including androgen receptor antagonists, are clinically used to treat patients with prostate cancer. However, most hormone-dependent prostate cancer patients progress into a malignant state with loss of hormone-dependency, known as castration (drug)-resistant prostate cancer (CRPC), after prolong androgen-based treatments. Even in the CRPC state with irreversible malignancy, androgen receptor (AR) expression is detectable. An epigenetic transition to CRPC induced by the action of AR-mediated androgen could be speculated in the patients with prostate cancer. Androgen receptors belongs to the nuclear receptor superfamily with 48 members in humans, and acts as a ligand-dependent transcriptional factor, leading to local chromatin reorganization for ligand-dependent gene regulation. In this review, we discussed the transcriptional/epigenetic regulatory functions of AR, with emphasis on the clinical applications of AR ligands, AR protein co-regulators, and AR RNA coregulator (enhancer RNA), especially in chromatin reorganization, in patients with prostate cancer

Anti-inflammatory effects of hyaluronan in arthritis therapy: Not just for viscosity

Hyaluronic acid (HA) has been widely used for viscosupplementation of diseased or aged articular joints. However, recent investigations have revealed the active anti-inflammatory or chondroprotective effect of HA, suggesting its potential role in attenuation of joint damage. In particular, interactions between HA and other inflammatory mediators are attracting interest. This review summarizes several aspects of recent investigations of the anti-inflammatory effects of HA in arthritis