{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T07:21:45Z","timestamp":1783840905270,"version":"3.55.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T00:00:00Z","timestamp":1699574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>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-\u03b1, TGF-\u03b21, IL-10, IL-6, and IFN-\u03b3, 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-\u03b1 -308 G\/A polymorphisms was significantly lower in patients versus controls. Moreover, the genotypic frequency of TNF-\u03b1 -308G\/A and TGF-\u03b2 gene codon 25 G\/C genotypes was significantly lower in patients versus controls. Considering cytokine SNP genotypes associated with different gene expression levels, TNF-\u03b1 high gene expression was significantly more frequent in patients, TGF-\u03b2 and IL-10 high gene expression was higher in patients with more severe anemia, and TGF-\u03b2 high gene expression was higher in patients with active disease. Considering treatment, TNF-\u03b1 and TGF-\u03b2 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-\u03b1 and TGF-\u03b2 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.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1221582","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T11:49:43Z","timestamp":1699876183000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Cytokine polymorphisms in patients with autoimmune hemolytic 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