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LINKING AUTOIMMUNITY WITH ALLOIMMUNITY

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

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javier carboneThe 8th International Congress on Autoimmunity held in Granada, Spain (9-13 May, 2012) provided physicians, immunologists, rheumatologists, researchers, and clinicians interested in autoimmune diseases with a forum where they could present their views on the latest available diagnostic and therapeutic tools.

Alloimmunity and autoimmunity share a number of important afferent, effector, and regulatory immunological pathways. Knowledge of the mechanisms underlying autoimmune diseases may help us to understand alloimmune reactions.

Furthermore, recent advances in the control of autoimmune diseases are potentially useful in transplant medicine and vice versa. Here, we provide some examples.

Intravenous immunoglobulin (IVIG) is increasingly used both as substitutive and immunomodulatory therapy in solid organ transplantation; however, uncertainties about its mechanism of action continue to be a barrier. The final session of the congress (Dr. De Groot) included an interesting presentation about T regitopes, which are present in both the Fc and Fab fractions of IgG. Knowledge of these highly promiscuous major histocompatibility complex class II T-cell epitopes that are capable of specifically activating CD4(+)CD25(Hi)FoxP3(+) natural regulatory T cells may clarify the immunomodulatory mechanism of action of IVIG.

Rituximab is increasingly used in desensitization protocols in solid organ transplantation. july linksImmune monitoring to identify potential candidates for rituximab from among patients with rheumatoid arthritis who are at risk of developing severe infection is yet another interesting application for transplant medicine. Studies of large cohorts of rheumatoid arthritis patients treated with rituximab have shown that severe IgG hypogammaglobulinemia is a risk factor for severe infection. The indication for rituximab should be carefully balanced in such cases, since IgG hypogammaglobulinemia (sometimes severe) can appear in heart and lung recipients in the first few months after transplantation.

Short courses of anti-CD25 (the alpha-chain of the IL-2 receptor) are increasingly used as induction therapy in solid organ transplantation with good control of alloimmune responses. With regard to manipulation of the IL-2 receptor axis to induce tolerance, Professor Abbul K Abbas suggested that low-dose interleukin-2 had the potential to expand regulatory functions. This immunomodulatory strategy is being tested in cancer therapy, bone marrow transplantation, and autoimmune diseases. Low-dose interleukin-2 has been shown to lead to T regulatory cell recovery and concomitant clinical improvement in patients with HCV-induced vasculitis, an autoimmune condition. A key issue is the definition of a dose of interleukin-2 that is highly selective for human Tregs while avoiding or minimizing stimulatory effects on T effector cell responses. It is interesting that we now consider using a pro-inflammatory cytokine to regulate inflammatory conditions in autoimmune diseases (some years ago this idea would have been considered very risky).

These are excellent examples of the complexity of the immune system and the possibilities to regulate alloimmunity even with seemingly paradoxical interventions.


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