The pursuit of transplantation tolerance: new mechanistic insights
CELLULAR & MOLECULAR IMMUNOLOGY
Authors: Gupta, Pawan K.; McIntosh, Christine M.; Chong, Anita S.; Alegre, Maria-Luisa
Abstract
Donor-specific transplantation tolerance that enables weaning from immunosuppressive drugs but retains immune competence to non-graft antigens has been a lasting pursuit since the discovery of neonatal tolerance. More recently, efforts have been devoted not only to understanding how transplantation tolerance can be induced but also the mechanisms necessary to maintain it as well as how inflammatory exposure challenges its durability. This review focuses on recent advances regarding key peripheral mechanisms of T cell tolerance, with the underlying hypothesis that a combination of several of these mechanisms may afford a more robust and durable tolerance and that a better understanding of these individual pathways may permit longitudinal tracking of tolerance following clinical transplantation to serve as biomarkers. This review may enable a personalized assessment of the degree of tolerance in individual patients and the opportunity to strengthen the robustness of peripheral tolerance.
Large B-Cell Lymphoma With IRF4 Rearrangement: From Theory to Practice
AJSP-REVIEWS AND REPORTS
Authors: Vincent, Gabriel; Richebourg, Steven; Cloutier, Stephanie; Fortin, Melanie; Jacob, Simon; Amin-Hashem, Mohamed
Abstract
Interferon regulatory factor 4 (IRF4) rearrangement is a common cytogenetic anomaly reported in various neoplastic lymphoproliferative disorders. IRF4 is a gene located on chromosome 6 that encodes for the IRF4 protein belonging to the IRF family of transcription factors. Large B-cell lymphoma with IRF4 rearrangement constitutes a novel provisional entity included in the classification of lymphoid tissue recently proposed by the World Health Organization in its fourth revised edition. This rare entity, with a specific clinical presentation, is defined by the presence of a rearrangement of the IRF4 gene. We report a rare case of a 19-year-old female patient presenting with a large B-cell lymphoma with IRF4 rearrangement located in the right tonsil, with characteristic histologic appearance and the phenotype of neoplastic cells. The presence of an IGH-IRF4 rearrangement was also confirmed, using a fluorescence in situ hybridization analysis with 2 successive hybridizations on the same slide. Patient was treated with 6 cycles of R-CHOP with no evidence of recurrence.