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Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
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Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
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MIF functional polymorphisms are associated with acute GVHD progression and steroid-refractoriness.

Aviran Aharon1, Batia Avni2, Daniel Louzoun1

  • 1Hebrew University-Hadassah Faculty of Medicine, Jerusalem, Israel.

Frontiers in Immunology
|May 27, 2025
PubMed
Summary

High expression genotypes of macrophage migration inhibitory factor (MIF) are linked to worse graft versus host disease (GVHD) after stem cell transplants. These findings may help identify patients at risk for steroid-refractory GVHD.

Keywords:
HSCTMIFacute GVHDpolymorphismsteroid-refractory

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High Throughput Sequential ELISA for Validation of Biomarkers of Acute Graft-Versus-Host Disease
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Area of Science:

  • Immunology
  • Transplantation Medicine
  • Genetics

Background:

  • Graft versus host disease (GVHD) affects about 50% of allogeneic hematopoietic stem cell transplantation (HSCT) recipients.
  • Glucocorticoids (GC) are the primary treatment, but steroid-refractory (SR) GVHD has a poor prognosis.
  • Macrophage migration inhibitory factor (MIF) plays a role in immune reactions and can counteract GC's anti-inflammatory effects.

Purpose of the Study:

  • To investigate the association between functional polymorphisms in the MIF gene and the development of acute GVHD (aGVHD) after allogeneic HSCT.
  • To determine if MIF gene polymorphisms and serum levels can predict steroid-refractory aGVHD.

Main Methods:

  • Analyzed two functional polymorphisms in the MIF gene (-794 CATT5-8 and -173 G/C) in 86 allogeneic HSCT patients.
  • Measured MIF serum levels at various time points before and after HSCT.

Main Results:

  • Increased frequencies of high-expression MIF genotypes (-794 CATT7) were observed in patients with grade III-IV aGVHD compared to those without or with grade II aGVHD.
  • MIF-794 CATT7 and -173 C genotypes were significantly associated with steroid-refractory aGVHD.
  • Elevated circulating MIF levels were found to precede the onset of severe aGVHD.

Conclusions:

  • Genetically determined high MIF expression is associated with the worsening of aGVHD.
  • MIF genotypes may serve as a predictive biomarker for identifying patients with steroid-refractory disease, potentially improving treatment strategies.