title: Desmoplakin and KIF20B as target antigens in patients with paroxysmal nocturnal haemoglobinuria.
abstract: At least two hypotheses have been proposed to explain the mechanism of clonal expansion of mutant cells in paroxysmal nocturnal haemoglobinuria (PNH). One hypothesis assumes an immune escape mechanism and another proposes an intrinsic second mutational event within clonal cells. We hypothesised 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 serological reactivity against haematopoietic stem/progenitor cells antigens using the SEREX approach. Two antigens were identified that are constitutively expressed in CD34(+) cells. Three and four of 10 PNH patients showed antibody responses against kinesin family member 20B (KIF20B) (previously termed 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 KIF20B or desmoplakin was detected in five patients with aplastic anaemia without a glycosyl phosphatidyl inositol -deficient clone. We conclude that KIF20B and desmoplakin have been shown to be the first known auto-antigens to be recognised 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.
authors.affiliation: Jose-Carrerase-Center for Immuno- and Genetherapy, Department of Internal Medicine Ι, Saarland University Medical School, Homburg, Germany.
authors.forename: Adnan
authors.initials: A
authors.lastname: Alahmad
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Preuss
authors.forename: Joachim
authors.initials: J
authors.lastname: Schenk
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Füreder
authors.forename: Hubert
authors.initials: H
authors.lastname: Schrezenmeier
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Müller-Lantzsch
authors.forename: Jörg
authors.initials: J
authors.lastname: Schubert
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000097:blood; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D048429:Cell Size; D051180:Desmoplakins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004912:Erythrocytes / Q000473:pathology; D005260:Female; D017261:Glycosylphosphatidylinositols / Q000172:deficiency; D006098:Granulocytes / Q000473:pathology; D006457:Hemoglobinuria, Paroxysmal / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016547:Kinesins / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D001323:Autoantibodies; D001324:Autoantigens; C495294:DSP protein, human; D051180:Desmoplakins; D017261:Glycosylphosphatidylinositols; D007074:Immunoglobulin G; C438388:KIF20B protein, human; D016547:Kinesins