Rheumatoid Arthritis: Moynet D

Rambert J, Mamani-Matsuda M, Moynet D, Dubus P, Desplat V, Kauss T, Dehais J, Schaeverbeke T, Ezzedine K, Malvy D, Vincendeau P, Mossalayi MD. · Groupe Thérapeutiques d'inflammation et d'infection, Laboratoire d'Immunologie et de Parasitologie, UFR Sciences Pharmaceutiques, Université Bordeaux 2, Bordeaux, France. · PLoS One. · Pubmed #19279679 links to  free full text

Abstract: BACKGROUND: CD23 is a differentiation/activation antigen expressed by a variety of hematopoietic and epithelial cells. It can also be detected in soluble forms in biological fluids. Initially known as the low-affinity receptor for immunoglobulin E (Fc epsilonRII), CD23 displays various other physiologic ligands such as CD21, CD11b/c, CD47-vitronectin, and mannose-containing proteins. CD23 mediates numerous immune responses by enhancing IgE-specific antigen presentation, regulating IgE synthesis, influencing cell differentiation and growth of both B- and T-cells. CD23-crosslinking promotes the secretion of pro-inflammatory mediators from human monocytes/macrophages, eosinophils and epithelial cells. Increased CD23 expression is found in patients during allergic reactions and rheumatoid arthritis while its physiopathologic role in these diseases remains to be clarified. METHODOLOGY/PRINCIPAL FINDINGS: We previously generated heptapeptidic countrestructures of human CD23. Based on in vitro studies on healthy and arthritic patients' cells, we showed that CD23-specific peptide addition to human macrophages greatly diminished the transcription of genes encoding inflammatory cytokines. This was also confirmed by significant reduction of mediator levels in cell supernatants. We also show that CD23 peptide decreased IgE-mediated activation of both human and rat CD23(+) macrophages. In vivo studies in rat model of arthritis showed that CD23-blocking peptide ameliorates clinical scores and prevent bone destruction in a dose dependent manner. Ex-vivo analysis of rat macrophages further confirmed the inhibitory effect of peptides on their activation. Taken together our results support the role of CD23 activation and subsequent inflammatory response in arthritis. CONCLUSION: CD23-blocking peptide (p30A) prevents the activation of monocytes/macrophages without cell toxicity. Thus, targeting CD23 by antagonistic peptide decreases inflammatory markers and may have clinical value in the treatment of human arthritis and allergic reactions involving CD23.

Beby-Defaux A, Frugier F, Bourgoin A, Moynet D, Hajjar C, Sainte-Foie S, Guillemain B, Agius G. · Laboratoire de Microbiologie B, EA 1720 Interactions Agents Infectieux-Hôtes, Centre Hospitalier Universitaire, Poitiers, France. · J Med Virol. · Pubmed #10459164 No free full text.

Abstract: Human T-cell lymphotropic virus type I (HTLV-I) is associated with adult T-cell leukemia (ATL) and tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). Other inflammatory disorders may occur in HTLV-I-infected patients, such as sicca syndrome resembling Sjögren's syndrome. The sicca syndrome may be the unique clinical manifestation of HTLV-I infection, but is associated frequently with TSP/HAM, which could suggest that sicca syndrome might be an early event in disease progression to TSP/HAM in some cases. We investigated whether peculiar pX and LTR mutations could be related to sicca syndrome, or might argue the existence of clinical progression to TSP/HAM. pX, especially pX(I), pX(II), and pX(IV) ORFs corresponding to Tax cytotoxic T-lymphocyte epitopes, and LTR regions from Caribbean patients who have sicca syndrome with or without TSP/HAM, ATL patients, and healthy carriers were sequenced. The sequences were aligned and compared with ATK-1 prototype and published sequences. LTR sequences exhibited 1.5-2.4% of divergence with ATK-1. pX-sequenced regions showed a lower homology within p12(I) encoding sequences. Only few mutations were found within functionally important regions, but were not associated specifically with the clinical status. Finally, no mutations that could be related to sicca syndrome or argue the existence of clinical progression to TSP/HAM were found. It would be of interest to study the clinical evolution of HTLV-I-sicca syndrome in patients and to determine HTLV-I sequences from peripheral blood and salivary glands at different stages.