Desmoplakin and MPP1 as target antigens in patients with Paroxysmal nocturnal Hemoglobinuria

Adnan Alahmad (1) , Klaus-Dieter Preuss (1) , Joachim Schenk (2) , Wolfgang Füreder (3) , Hubert Schrezenmeier (4) , Nikolaus Müller-Lantzsch (5) , Michael Pfreundschuh (1) , Jörg Schubert (6)

1 Internal medicine I
2 Department of transfusion medicine
3 Department of Haematology and Haemostaseology
4 Institute for transfusion medicine and Immunogenetic Clinics for Aplastic Anaemia
5 Department of Virology [Homburg]
6 Department of haematology and oncology

Several hypotheses have been proposed to explain the mechanism of clonal expansion of mutant cells in paroxysmal nocturnal Hemoglobinuria (PNH). One hypothesis assumes an immune escape mechanism and the other proposes an intrinsic second mutational event within clonal cells. We hypothesized that autoantibodies detected in PNH patients could identify antigens that might play a role in the pathophysiology of this disease and screened a human fetal liver cDNA library for serologic reactivity against hematopoietic stem/ progenitor cells antigens using the SEREX approach. Two antigens were identified which are constitutively expressed in CD34+ cells. Three and four of 10 PNH patients showed antibody responses against M-phase phosphoprotein 1 (MPP1) and desmoplakin (DSP) respectively. We also found an antibody response in one of 20 healthy volunteers against desmoplakin, yet at a much lower titre than in PNH patients. No response to MPP1 or desmoplakin was detected in five patients with aplastic anaemia without a GPI-deficient clone. We conclude that MPP1 and desmoplakin are the first auto-antigens shown to be recognized by the immune system of patients with PNH. The analysis of the mechanisms underlying the autoimmune response might contribute to our understanding of the clonal expansion in PNH.

Mots clés: Medicine

Adnan Alahmad, Klaus-Dieter Preuss, Joachim Schenk, Wolfgang Füreder, Hubert Schrezenmeier, et al.. Desmoplakin and MPP1 as target antigens in patients with Paroxysmal nocturnal Hemoglobinuria. British Journal of Haematology, 2010, 151 (3), pp.273. ⟨10.1111/j.1365-2141.2010.08345.x⟩. ⟨hal-00573090⟩