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

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Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

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.

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Abbreviations

HSCs:

Hematopoietic stem cells

ISAA/PNH:

Initial severe aplastic anemia domination PNH

CD:

Cluster of differentiation

DNA:

Deoxyribonucleic acid

FITC:

Fluorescein isothiocyanate

GPI:

Glycosyl-phosphatidylinositol

HLA:

Human leukocyte antigens

IBGRL:

International Blood Group Reference Laboratory

LDH:

Lactate dehydrogenase

MHC:

Major histocompatibility complex

NADH:

Nicotinamide adenine dinucleotide, reduced

n/PNH:

Non-aplastic anemia type PNH

p corr :

Corrected p

PCR:

Polymerase chain reaction

PIG-A :

Phosphatidylinositol glycan complementation group A gene

PLD:

Phosphatidylinositol-glycan-specific phospholipase D

PNH:

Paroxysmal nocturnal hemoglobinuria

RBCs:

Red blood cells

SSP:

Sequence specific primers

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Authors and Affiliations

  1. Department of Immunogenetics, Institute of Hematology and Transfusion Medicine, 14 Indira Gandhi Street, 02-776, Warsaw, Poland

    Jacek Nowak, Renata Mika-Witkowska, Marta Rogatko-Koroś, Elżbieta Graczyk-Pol & Małgorzata Wójcik

  2. Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland

    Ewa Mendek-Czajkowska

  3. Department of Immunohematology and Immunology of Transfusion Medicine, Institute of Hematology and Transfusion Medicine, Warsaw, Poland

    Hanna Pyl, Aneta Klimczak & Barbara Żupańska

  4. Laboratory of Pathomorphology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland

    Monika Prochorec-Sobieszek & Renata Maryniak

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  1. Jacek Nowak
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  2. Renata Mika-Witkowska
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Correspondence to Jacek Nowak.

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Nowak, J., Mika-Witkowska, R., Mendek-Czajkowska, E. et al. The Patterns of MHC Association in Aplastic and Non-aplastic Paroxysmal Nocturnal Hemoglobinuria. Arch. Immunol. Ther. Exp. 59, 231–238 (2011). https://doi.org/10.1007/s00005-011-0125-2

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