AUTHOR=Zaninoni Anna , Fattizzo Bruno , Pettine Loredana , Vercellati Cristina , Marcello Anna P. , Barcellini Wilma 

TITLE=Cytokine polymorphisms in patients with autoimmune hemolytic anemia

JOURNAL=Frontiers in Immunology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1221582

DOI=10.3389/fimmu.2023.1221582

ISSN=1664-3224

ABSTRACT=Autoimmune hemolytic anemia (AIHA) is due to autoantibodies with or without complement activation and involves cellular and cytokine dysregulation. Here we investigated cytokine single nucleotide polymorphisms (SNPs) of TNF-α, TGF-β1, IL-10, IL-6, and IFN-γ, along with their serum levels. The formers were related to hematological parameters, therapy, and clinical outcome. The study included 123 consecutive patients with primary AIHA (77 warm AIHA and 46 cold agglutinin disease, CAD), followed-up for a median of 49 months. Results show that the allelic frequency of TNF-α -308 G/A polymorphisms were significantly lower in patients versus controls. Moreover, the genotypic frequency of TNF-α -308G/A and TGF-β gene codon 25 G/C genotypes were significantly lower in patients versus controls. Considering cytokine SNPs genotypes associated with different gene expression levels, TNF-α high gene expression was significantly more frequent in patients, TGF-β and IL-10 high gene expression were higher in patients with more severe anemia, and TGF-β high gene expression was higher in patients with active disease. Considering treatment, TNF-α and TGF-β high gene expression were more frequent in multi-treated patients and particularly in CAD. It may be speculated that this genetic predisposition to a stronger inflammatory response may result in a greater immune dysregulation and in a relapsed/refractory disease. Regarding cytokine serum levels, TNF-α and TGF-β were significantly lower, IL-10 and IL-6 significantly higher in patients versus controls, underlying the complex interplay between genetic background and disease features.