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Linking Transplant Medicine With
Primary Immunodeficiencies

Javier Carbone, MD, PhD
University Hospital Gregorio Marañon
Transplant Immunology Group
Madrid, Spain

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The 15th Congress ( of the European Society for Immunodeficiencies (ESID) held in Florence, Italy (3-6 October, 2012) encompassed innovations in diagnostic immunology, genetics and immunobiology of primary immunodeficiencies (PID). Advances in clinical practice, novel therapeutic approaches to tolerance induction, and new insights into stem-cell and cellular therapies were covered by experts in this field.

PID are diseases caused by inherited defects of the immune system. Advances in medical research have led to the identification of more than 140 genes which cause more than 200 different forms of PID. The wide spectrum of PID states seen in adult and children highlights the need for increased awareness of their existence. Knowledge of the mechanisms underlying PID may help us to understand the function of the distinct effector functions of the immune system. Furthermore, recent advances in the control of PID are potentially useful in transplant medicine.

november links imageInteresting new PID described in this congress included human IL-21R deficiency (Uzel et al), which highlighted IL-21's critical role in the host defense against cryptosporidium and Pneumocystis, and STAT2 deficiency as a novel immunodeficiency that predisposes to viral infections (Hambleton et al). Toll-like receptors (TLRs) activate biochemical pathways that evoke activation of innate immunity, which leads to dendritic cell maturation and initiation of adaptive immune responses that provoke allograft rejection. Walter et al. described a murine model of dysregulation after infection in which TLR3 stimulation resulted in cytokine storm and increased autoantibody production.

Intravenous immunoglobulin (IVIG) can be used as substitutive therapy in solid organ transplantation. In PID patients receiving IVIG, Bexon et al reported on increased frequency of infections at the end of the IVIG dosing cycle. These authors demonstrated that the frequency of infection varies by week, with the highest frequency of infections at the end of 3- or 4-week dosing cycles. This suggest a "wear-off" effect, reflecting the immunoglobulin serum concentration profile associated with intravenous administration, which is characterized by pronounced peak and trough levels. This information could be taking into account when using IVIG in transplant recipients with post-transplant antibody deficiencies.

Immune monitoring to identify potential candidates for rituximab who are at risk of developing severe hypogammaglobulinemia is yet another potential interesting application for transplant medicine. E Villegas et al demonstrated the possible correlation between immunoglobulin levels after Rituximab treatment and the FCGR3A-158V/F polymorphism. If this observation is confirmed it could be useful to identify patients at higher risk of developing secondary hypogammaglobulinaemia after Rituximab usage.

Disclosure Statement: The author has no relevant financial relationships to disclose.