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Blood, 15 January 2008, Vol. 111, No. 2, pp. 483.
Unraveling the immune response during AIHAUNIVERSITY OF THE WEST OF ENGLAND
In this issue of Blood, Ward and colleagues make some novel fundamental observations on the nature of the immune response during autoimmune hemolytic anemia (AIHA). They show a key role for T regulatory cells (Tregs) in the pathogenesis of this autoimmune disease.
The management of autoimmune diseases represents a major challenge to medicine in the 21st century. These diseases constitute a major cause of long-term dehabilitation, and the only effective treatment is often global immunosuppression, which has considerable, sometimes disastrous, side effects. AIHA is a classical example of such conditions, and front-line treatment almost invariably requires immunosuppression involving administration of corticosteroids and sometimes even splenectomy.2,3 In extreme cases, AIHA can cause significant problems during transfusion, as panagglutinating or red cell–bound autoantibodies interfere with crossmatching and may reduce the effectiveness of transfusion due to the production of alloantibodies.4 A better understanding of the pathogenesis of the aberrant immune response to autoantigens is a long-term goal in the treatment of AIHA and other autoimmune diseases.
AIHA is the first disease in which Tregs have been identified to respond to autoantigen—a peptide epitope derived from the human red cell Rh proteins. Ward et al confirm that one hallmark of Tregs involved in the pathology of AIHA is that they express IL-10 and the transcription factor FoxP3. However, more importantly, the authors confirm that autoreactive Tregs show discrete phenotypic differences that indicate they derive from a Th1 effector T-cell population specific for the Rh proteins, a result that warrants further investigation. Ward et al also demonstrate that CTLA-4 ligation costimulates (along with interaction with the TCR) the isolated Tregs to express cytokines (IL-10 and IFN-
Footnotes
Conflict-of-interest disclosure: The author declares no competing financial interests.
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| Copyright © 2008 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
) involved in their further proliferation. Now that the individual cells and their surface markers involved in the pathogenesis of AIHA have been defined, further studies may reveal precisely how effector cells that promote inflammation switch to tolerance-inducing Tregs during the course of disease. This will ultimately lead to better regimes for the clinical management of autoimmunity, which currently lacks specific therapies. 