The special role of anti-ADAMTS13-IgA in acquired TTP: Production induced by infectious microorganisms?

J. Falk, T. Vigh, I. Scharrer (Mainz, Germany)

Platelets - Physiology and Disorders of platelet number and function
Date: 17.02.2017,
Time: 17:15 - 18:15

Objective: Thrombotic thrombocytopenic purpura (TTP) is a rare syndrome involving the production of thrombi in the microvasculature accompanied by thrombocytopenia and symptoms of organ ischemia. Acquired TTP develops when a patient produces antibodies which react with the protease Adamts13. IgG antibodies have been shown to dominate the immune response in TTP. In order to further assess their clinical implications we conducted a study analyzing the anti-Adamts13 antibody isotypes IgG, IgA and IgM in patients suffering from acquired TTP.

Methods: Plasma samples from 9 patients suffering an acute TTP episode and 27 patients in remission were analyzed. Additionally, medical histories and available documentation of treatment, clinical course and laboratory data were obtained. Patients were recruited at the Department of Hematology at the University Medical Center, Johannes Gutenberg University Mainz, Germany. IgM and IgA anti-Adamts13 antibodies were analyzed by modifications to the ImubindĀ® Elisa kit for anti-Adamts13 IgG.

Results: Three of the 9 patients analyzed during an acute episode were positive for anti-ADAMTS13-IgA. We observed a higher occurrence of severe disease (qualified as number of plasma exchange procedures and duration of inpatient treatment) in these patients. The only two patients suffering an acute episode and showing detectable anti-Adamts13 IgA and anti-Adamts13 IgG were also the only two patients with an infectious disease as trigger factor for the episode. Of the 27 remission patients three were also positive for anti-Adamts13 IgA. An infectious disease had also preceded their last episode.

Conclusion: Eventhough our data is based on a limited number of patients our results indicate that anti-Adamts13 IgA may be of particular significance in TTP. For one, patients with IgA appeared at higher risk for severe disease. Interestingly, Tiede et al. recently found the antibody isotype IgA against factor VIII in acquired hemophilia A to also be associated with poor prognosis (Tiede A, Hofbauer CJ, Werwitzke S, et al. Anti-factor VIII IgA as a potential marker of poor prognosis in acquired hemophilia A: results from the GTH-AH 01/2010 study. Blood 2016;127:2289-2297.). Secondly, we observed a possible link between infectious triggers and production of anti-Adamts13 antibodies of type IgA in acute TTP.