Paroxysmal nocturnal hemoglobinuria: Significant association with specific HLA-A, -B, -C, and -DR alleles in an Italian population

• Published in: Human immunology 2008-03, Vol.69 (3), p.202-206
• Main Authors: Lombardi, Maria Luisa, Terrazzano, Giuseppe, Cosentini, Elena, Gargiulo, Lucia, Risitano, Antonio, Camerlingo, Rosa, Sica, Michela, Aufiero, Daniela, Poggi, Alessandro, Pirozzi, Giuseppe, Luzzatto, Lucio, Rotoli, Bruno, Notaro, Rosario, Alfinito, Fiorella, Ruggiero, Giuseppina
• Format: Article
• Language: English
• Subjects: Adult; Aged; Alleles; Allergy and Immunology; Female; Gene Frequency; Haplotype; Haplotypes; Hemoglobinuria, Paroxysmal - genetics; HLA; HLA-A Antigens - genetics; HLA-B Antigens - genetics; HLA-C Antigens - genetics; HLA-DQ Antigens - genetics; HLA-DR Antigens - genetics; Humans; Immune-mediated disease; Italy; Male; Middle Aged; PNH
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2008.02.001

Summary Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by the expansion of a PIG-A mutated hematopoietic stem cell. An immune-mediated origin has been suggested for this disease. Because HLA genes represent a susceptibility factor for autoimmunity, we investigated HLA genotype in 42 Italian PNH patients compared with 301 control subjects of the same ethnic origin. A significantly increased frequency of the HLA class I alleles A*0201 ( p < 0.05), B*1402 ( p < 0.001), and Cw*0802 ( p < 0.005), and of the HLA class II DRB1*1501 ( p < 0.01) with the linked DQB1*0602 ( p ≤ 0.05) and DRB1*01 ( p ≤ 0.05) with the linked DQB1*0501 ( p ≤ 0.01) alleles, has been observed. Notably, a fourfold increase of the haplotype B*1402, Cw*0802 ( p < 0.0005) and a 15-fold increase of the Mediterranean haplotype A*33, B*1402, Cw*0802, DRB1*0102, DQB1*0501 ( p < 0.005) was also revealed. This association may provide new insights into the autoimmune pathogenesis of PNH.