Cytokine polymorphisms in patients with autoimmune hemolytic anemia

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-alpha, TGF-beta 1, IL-10, IL-6, and IFN-gamma, along with their serum levels. The former 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-alpha -308 G/A polymorphisms was significantly lower in patients versus controls. Moreover, the genotypic frequency of TNF-alpha -308G/A and TGF-beta gene codon 25 G/C genotypes was significantly lower in patients versus controls. Considering cytokine SNP genotypes associated with different gene expression levels, TNF-alpha high gene expression was significantly more frequent in patients, TGF-beta and IL-10 high gene expression was higher in patients with more severe anemia, and TGF-beta high gene expression was higher in patients with active disease. Considering treatment, TNF-alpha and TGF-beta high gene expression was more frequent in multitreated 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-alpha and TGF-beta were significantly lower, and IL-10 and IL-6 were significantly higher in patients versus controls, underlying the complex interplay between genetic background and disease features.