Advances in basic and clinical immunology in 2011

Abstract

Investigations of basic immunologic mechanisms and clinical studies of primary immunodeficiencies were most prevalent in 2011. Significant progress was achieved in the characterization of T(H)17 cell differentiation and associated cytokines in the setting of inflammatory disorders, HIV infection, and immunodysregulation disorders. The role of transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) mutations in the pathogenesis of CVID was further described and reported to be likely mediated by impaired TACI expression affecting B-cell function. The frequency of autoimmunity in patients with partial DiGeorge syndrome was estimated at 8.5%, predominantly resulting in blood cytopenias and hypothyroidism. Several reports emphasized the presentation of neoplasias, most often lymphomas, as the first manifestation of several primary immunodeficiencies. Novel strategies for newborn screening of B-cell lymphopenia by measuring immunoglobulin κ chain-deletion recombinant excision circles and for adenosine deaminase deficiency using tandem mass spectrometry were demonstrated to be feasible at a large scale. Progress in the treatment of primary immunodeficiencies included increased success with unrelated HLA-compatible donors for hematopoietic stem cell transplantation and the development of new gene therapy approaches with improved safety features. Induced pluripotent stem cells were developed from patients with primary immunodeficiencies, providing a virtually unlimited resource for pathophysiology and gene correction studies. New findings in several of the uncommon immunodeficiencies, such as the increased susceptibility to severe viral infections caused by defects in the activation of the Toll-like receptor 3 pathway, overall contributed to the understanding of their immunologic basis and provided for the design of effective diagnostic and therapeutic strategies.