Project 1 is to improve the quantity and quality of immune-phenotypic data of peripheral lymphocyte subsets from PAD patients. Currently, the flow cytometric analysis is performed by different laboratories using different panels of monoclonal antibodies. A standardized assessment is underway. Results of this subproject can be viewed on the new website www.ipidnet.org.
Project 2 is to define genetic variations in PAD patients with agammaglobulinemia and low B cell counts who do not have a definitive genetic/molecular diagnosis by the analysis of specific points of arrest of B cell differentiation in the bone marrow.
We have undertaken bone marrow biopsy and FACS immunophenotyping in patients with CVID in order to assess if the clinical and immunological phenotype correlates with a specific developmental block/alteration in the early stages of B cell development. Our preliminary data are very interesting and promising: early B cell development in CVID is disturbed at different stages in a large percentage of CVID patients and apparently more patients share a similar developmental defect.
Project 3 is to analyse the role of the different B lymphocyte subpopulations in the protection from infections by encapsulated bacteria. We showed that IgM anti PnPS antibodies in PAD correlate with the capacity to differentiate into plasmablasts. We also demonstrated that a reduced proliferative response to CpG correlates with an increased lung infection rate. Due to the impaired proliferative responde, CpG induced plasmablast differentiation is decreased in patients with CD21low (>10%).
Project 4 is to define quantitative and qualitative antibody defects in PAD patients.
Project 5 is to identify biomarkers to predict the risk of infusion reaction in PAD patients. Anti-IgA antibodies have been proposed as predictive factors for the occurrence of adverse reactions to IgG replacement therapy which contains traces of IgA in PAD patients, but their pathogenetic role and their isotype (IgG vs IgE) is still unclear.