CTLA4Fcε, a novel soluble fusion protein that binds B7 molecules and the IgE receptors, and reduces human in vitro soluble CD23 production and lymphocyte proliferation.

Immunoglobulin E-mediated allergy and certain autoimmune diseases are characterized by the presence of a T helper type 2 (Th2) immune response and allergen-specific or self-reactive IgE. Soluble CD23 (sCD23) is a B-cell factor that fosters IgE class-switching and synthesis, suggesting that sCD23 may be a therapeutic target for these pathologies. We produced a recombinant protein, CTLA4Fcε, by fusing the ectodomain of the immunoregulatory molecule cytotoxic T-lymphocyte antigen 4 (CTLA-4) with a fragment of the IgE H-chain constant region. In SDS-PAGE/inmunoblot analyses, CTLA4Fcε appeared as a 70,000 MW polypeptide that forms homodimers. Flow cytometry showed that CTLA4Fcε binds to IgE receptors FcεRI and FcεRII/CD23, as well as to CTLA-4 counter-receptors CD80 and CD86. Binding of CTLA4Fcε to FcεRII/CD23 appeared stronger than that of IgE. Since the cells used to study CD23 binding express CD80 and CD86, simultaneous binding of CTLA4Fcε to CD23 and CD80/CD86 seems to occur and would explain this difference. As measured by a human CD23-specific ELISA, CTLA4Fcε - but not IgE - induced a concentration-dependent reduction of sCD23 in culture supernatants of RPMI-8866 cells. Our results suggest that the simultaneous binding of CTLA4Fcɛ to CD23-CD80/CD86 may cause the formation of multi-molecular complexes that are either internalized or pose a steric hindrance to enzymatic proteolysis, so blocking sCD23 generation. CTLA4Fcε caused a concentration-dependent reduction of lymphocyte proliferation in human peripheral blood mononuclear cell samples stimulated in vitro with concanavalin A. The ability to bind IgE receptors on effector cells, to regulate the production of sCD23 and to inhibit lymphocyte proliferation suggests that CTLA4Fcɛ has immunomodulatory properties on human Th2 responses.

Osteoporosis: factores de riesgo, prevención y tratamiento / Osteoporosis risk factors, prevention and treatment

La osteoporosis es una enfermedad esquelética sistémica caracterizada por una baja densidad ósea y un deterioro de la microarquitectura del tejido óseo, con el consecuente aumento de la fragilidad y la susceptibilidad para la aparición de fracturas. Esta enfermedad afecta con mayor frecuencia a las mujeres posmenopáusicas, en una relacion mujer/hombre que puede variar entre 3 a 8 mujeres por cada hombre. Señalándose una incidencia de 25 por ciento para las mujeres mayores de 45 años y 50 por ciento para mujeres de 60 años. De acuerdo con datos de la Organización Mundial de la Salud, el número de personas mayores de 65 años ha aumentado considerablemente en los últimos años; conformado en la actualidad este grupo poblacional por cerca de 380 millones de personas, representando el 7 por ciento de la población total del mundo y de esta, 80 millones son mayores de 80 años. En la siguiente revisión la osteoporosis se expone como un problema de salud pública mundial, siendo el conocimiento de los factores de riesgo, prevención y tratamiento de importancia para la disminución y/o control de la enfermedad