Abstract

Paroxysmal Nocturnal Hemoglobinuria (PNH) is an acquired disorder characterized by the emergence and expansion of a GPI-defective clonal haematopoiesis. Its clinical features are haemolytic anaemia, cytopenia and thrombosis. Several data suggests the pathogenetic relevance for auto-immune-mediated mechanisms in the expansion of the mutated clone. Since HLA genes represent a susceptibility factor for autoimmunity, we have investigated HLA genotypes in 42 Italian patients with PNH. This study analyzed the HLA class I and class II genes in a cohort of 42 Italian PNH patients. Data indicate the occurrence of a significant increase of A*33 (9.5% in PNH patients versus 2.3% in controls; p<0.05), A*0201 (52.5% versus 32.2%; p<0.05), B*1402 (23.8% versus 5.3%; p<0.0005) and Cw*0802 alleles (23.8% versus 5.9%; p<0.001) in the PNH patient cohort, as compared with a population of 301 healthy controls of the same ethnical origin. In addition, an increased frequency of DRB1*1501 (21.1% versus 5.3%; p<0.005) and DRB1*01 (31.6% versus 10.9%; p<0.005), without specific association with the DRB1*0101 or DRB1*0102 allele, has been revealed. Notably, the B*1402, Cw*0802 (23.8% versus 5.3%; p<0.0005) HLA -B,-C haplotype was significantly increased. Moreover, the A*33, B*1402, Cw*0802, DRB1*0102 HLA-A, -B, -C, -DR haplotype shows a fifteen times increased frequency in PNH patients, if compared with controls (10.5% versus 0.66%; p<0.005). HLA polymorphism represents a main autoimmune susceptibility factor. In this context, our results suggest that specific peptide/s could be relevant for the selection/dominance of PIG-A mutated clones in our cohort of Italian PNH patients. Alternatively, the linkage of the described allele/s and haplotype with not yet characterized genes and/or with gene/s likely involved in pro-inflammatory cytokine productopn might be hypothesized. The association between certain HLA types and the occurrence of PNH may provide further insight into the mechanism for selective damage to normal (GPI+) hematopoiesis, which is responsible for the clonal expansion of GPI-defective hematopoiesis that ultimately gives rise to clinical PNH.

Author notes

Disclosure: No relevant conflicts of interest to declare.