The Patterns of MHC Association in Aplastic and Non-aplastic Paroxysmal Nocturnal Hemoglobinuria

  • Jacek Nowak
  • Renata Mika-Witkowska
  • Ewa Mendek-Czajkowska
  • Marta Rogatko-Koroś
  • Elżbieta Graczyk-Pol
  • Hanna Pyl
  • Aneta Klimczak
  • Małgorzata Wójcik
  • Monika Prochorec-Sobieszek
  • Renata Maryniak
  • Barbara Żupańska


The deficiency of glycosyl-phosphatidylinositol (GPI)-anchored proteins in plasma membranes of PIG-A gene mutated hematopoietic stem cells (HSCs) is so far insufficient to explain the domination of paroxysmal nocturnal hemoglobinuria (PNH) clone over the normal HSC. We attempted to elucidate possible link between MHC and initial severe aplastic anemia (ISAA/PNH) type and non-aplastic (n/PNH) outcome of PNH. In 50 PNH patients assigned as ISAA/PNH (n = 13), n/PNH (n = 33) or nonassigned (n = 4) and 200 ethnically matched controls we analyzed MHC associations. Our data confirmed strong associations of DRB1*15:01 (RR = 3.51, p = 0.0011) and DQB1*06:02 (RR = 7.09, p = 0.000026) alleles, especially with n/PNH subtype. B*18:01 allele was associated with increased risk of ISAA/PNH subtype (RR = 5.25, p = 0.0028). We conclude that both class II and class I MHC alleles are associated with different subsets of PNH. Clonal selection of PIG-A mutated cells with cognate metabolic block is associated with MHC class II alleles DRB1*15:01 and DQB1*06:02 independent from initial severe AA clone selection. MHC class I molecule B*18:01 can additionally influence the domination of PNH clone in PNH subjects with initial severe aplastic anemia.


Paroxysmal nocturnal hemoglobinuria Major histocompatibility complex Association study Bone marrow aplasia 



Hematopoietic stem cells


Initial severe aplastic anemia domination PNH


Cluster of differentiation


Deoxyribonucleic acid


Fluorescein isothiocyanate




Human leukocyte antigens


International Blood Group Reference Laboratory


Lactate dehydrogenase


Major histocompatibility complex


Nicotinamide adenine dinucleotide, reduced


Non-aplastic anemia type PNH


Corrected p


Polymerase chain reaction


Phosphatidylinositol glycan complementation group A gene


Phosphatidylinositol-glycan-specific phospholipase D


Paroxysmal nocturnal hemoglobinuria


Red blood cells


Sequence specific primers


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Copyright information

© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2011

Authors and Affiliations

  • Jacek Nowak
    • 1
  • Renata Mika-Witkowska
    • 1
  • Ewa Mendek-Czajkowska
    • 2
  • Marta Rogatko-Koroś
    • 1
  • Elżbieta Graczyk-Pol
    • 1
  • Hanna Pyl
    • 3
  • Aneta Klimczak
    • 3
  • Małgorzata Wójcik
    • 1
  • Monika Prochorec-Sobieszek
    • 4
  • Renata Maryniak
    • 4
  • Barbara Żupańska
    • 3
  1. 1.Department of ImmunogeneticsInstitute of Hematology and Transfusion MedicineWarsawPoland
  2. 2.Department of HematologyInstitute of Hematology and Transfusion MedicineWarsawPoland
  3. 3.Department of Immunohematology and Immunology of Transfusion MedicineInstitute of Hematology and Transfusion MedicineWarsawPoland
  4. 4.Laboratory of Pathomorphology, Institute of Hematology and Transfusion MedicineWarsawPoland

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