These recommendations are based on the consensus of clinical experts from a wide range of disciplines taking available evidence into account while balancing the benefits and risks of nonpharmacological, pharmacological, and surgical treatment modalities, and incorporating their preferences and values. Different backgrounds in terms of patient education or drug availability in different countries were not evaluated but will be important.

Knee articular cartilage samples obtained by arthroscopy from ten patients with well defined knee osteoarthritis (OA) were studied by light and transmission electron microscopy. The morphological phenotype of cells from fibrillated and non-fibrillated regions of OA cartilage was characterized. Three different cell sub-populations were identified. Type 1 cells were found in the superficial and upper middle zones and comprised single chondrocytes and cells organized in aggregates or "clones' that showed a typical chondrocyte phenotype. Type 2 cells displayed a secretory phenotype. Type 3 cells comprised chondrocytes undergoing a degenerative process and were distributed throughout all zones of the cartilage. Changes in the cytoskeletal arrangement, presence of abundant filopodia, peripheral localization of centrioles, and presence of primary cilia were found in many chondrocytes suggesting that they are active motile cells. No mitotic figures were found in this study. Morphometrical analysis was performed to determine the total number of cells and the number of chondrocytes per lacuna in the superficial and upper middle zones of fibrillated and non-fibrillated OA cartilage. There were no statistically significant differences in the total number of cells. In contrast, fibrillated OA cartilage contained a statistically significantly higher percentage of lacunae containing four of more chondrocytes than non-fibrillated OA cartilage samples. The absence of mitotic figures and the presence of motile elements in many chondrocytes raise the possibility that cell aggregates or "clones' in damaged OA cartilage originate by an active process of cell migration rather than by cellular division.

No abstract

(2016) Immunological evaluation of rheumatoid arthritis patients treated with itolizumab, mAbs, 8:1, 187-195, DOI: 10.1080/19420862.2015 To link to this article: https://doi.org/10. 1080/19420862.2015 Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation that affects approximately 1% of the general population. Itolizumab, a monoclonal antibody specific for the human CD6 molecule mainly expressed on T lymphocytes, has been shown to inhibit proliferation of T cells and proinflammatory cytokine production in psoriasis patients. We have now assessed the immunological effect of itolizumab in combination with methotrexate in rheumatoid arthritis by analyzing clinical samples taken from 30 patients enrolled in a clinical trial. T and B cell subpopulations were measured at different time points of the study. Plasma cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. The combined treatment of itolizumab and methotrexate led to a reduction in the frequency of T cell subpopulations, and plasma levels of proinflammatory cytokines showed a significant decrease up to at least 12 weeks after treatment ended. No anti-idiotypic antibody response was detected. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease.

IL-15 is a proinflammatory cytokine that acts early in the inflammatory response and has been associated with several autoimmune diseases including rheumatoid arthritis, where it had been proposed as a therapeutic target. We recently reported an IL-15 antagonist peptide corresponding to sequence 36-45 of IL-15 (KVTAMKCFLL) named P8, which specifically binds to IL-15Rα and inhibits IL-15 biological activity with a half maximal inhibitory concentration (IC50) of 130 µ m in CTLL-2 proliferation assay. In order to improve binding of peptide P8 to the receptor IL-15Rα, we used an Ala scan strategy to study contribution of each individual amino acid to the peptide's antagonist effect. Here, we found that Phe and Cys are important for peptide binding to IL-15Rα. We also investigated other single site mutations and replaced the second Lys in the sequence by the polar non-charged amino acid threonine. The resulting peptide [K6T]P8 exhibited a higher activity than P8 with an IC50 of 24 µm. We also found that this peptide was more active than peptide P8 in the inhibition of TNFα secretion by synovial cells from rheumatoid arthritis patients. The peptide [K6T]P8 described in this work is a new type of IL-15 antagonist and constitutes a potential therapeutic agent for rheumatoid arthritis.