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| Author(s): |
Anna Cristina Collanieri
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) |
| Defense date: | 2010-09-21 |
| Examining board members: |
Dewton de Moraes Vasconcelos;
Claudia Maria de Castro Gomes;
Cristina Maria Kokron;
Maria Notomi Sato;
Maria Marluce dos Santos Vilela
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| Advisor: | Dewton de Moraes Vasconcelos |
| Abstract | |
Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder of heterogeneous origin, defined by a decrease of at least two immunoglobulin isotypes, lack of antibody response to immunization and the exclusion of other causes of primary hypogammaglobulinemia. The absence of adequate levels of antibodies in patients with CVID results in recurrent bacterial infections, most frequently in the respiratory and digestive tract, which can lead to sinusal and lung sequels. Over the past six years the discovery of genes related to the phenotype of CVID began, such as the genes of TACI, BAFF-R, CD19 and ICOS. Among the immunological changes, there is impairment of memory B cells (CD19+/IgM-IgD-CD27+), leading to disturbance of isotypic switching and reduced secretion of immunogobulins. Currently this feature has been used to classify CVID. During the present study we observed that patients with CVID present changes in the expression of CD27 not only in B cells, but also in T cells, and reduced lymphoproliferative response to PHA. CD27 molecule is a member of the TNF family present constitutively in T cells, and after activation in B cells. Its importance in the immune response is related to the proliferation and co-activation of specific T cells that act in T-B interaction, in the T cell dependent B cells response. Thus disturbances in the CD27 pathway can result in defects in isotypic switch and differentiation of germinal center B cells, as well as memory cells. These characteristics can be observed in murine models of CD27/CD70 deficiency. Our findings allow a new approach for the study of CVID. The evaluation of defects in CD27/CD70 signaling in humans might become a new tool for understanding an incompletely understood disease. Such an approach may contribute to the development of new treatments, acting directly on the molecule in question. In addition, we also suggest the use of phenotyping of CD27 molecules on B and T lymphocytes, in addition to membrane IgM and IgD to characterize CVID, associated to the analysis of the molecule CD154 to exclude other immunodeficiencies (AU) | |