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Updated: Apr 17, 2026
High Throughput Sequential ELISA for Validation of Biomarkers of Acute Graft-Versus-Host Disease
Published on: October 31, 2012
Elevated level of HSPA1L mRNA correlates with graft-versus-host disease
Sadaf Atarod1, Brie Turner1, Kim Frances Pearce1
1Haematological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
Insights
Heat Shock Protein 70 family members show potential as biomarkers for graft-versus-host disease (GVHD) following allogeneic stem cell transplantation (allo-HSCT). HSPA1L mRNA in whole blood may predict chronic GVHD (cGVHD) in allo-HSCT patients.
Area of Science:
- Biomolecular research
- Transplantation immunology
- Molecular diagnostics
Background:
- Graft-versus-host disease (GVHD) is a serious complication of allogeneic stem cell transplantation (allo-HSCT).
- Current diagnostic methods for GVHD lack sufficient predictive biomarkers.
- Heat Shock Protein 70 (HSP70) family members are well-researched and may offer diagnostic potential.
Purpose of the Study:
- To investigate the biomarker potential of Heat Shock Protein 70 family members (HSPA1A/HSPA1B and HSPA1L) at the mRNA level.
- To evaluate these biomarkers in patients with acute GVHD (aGVHD) and chronic GVHD (cGVHD) after allo-HSCT.
- To determine if mRNA expression levels can predict GVHD development or severity.
Main Methods:
- Analysis of HSPA1L mRNA expression in skin biopsies from aGVHD patients and controls.
- Quantification of HSPA1L and HSPA1B mRNA levels in whole blood samples from allo-HSCT patients at various time points post-transplant.
- Statistical analysis including p-values and area under the curve (AUC) to assess biomarker significance.
Main Results:
- HSPA1L mRNA expression was reduced in skin biopsies of patients with severe aGVHD.
- HSPA1L mRNA in whole blood was significantly upregulated in cGVHD patients at 28 days post-transplant (p = 0.008, AUC = 0.773).
- HSPA1B mRNA in whole blood was elevated at 3 months post-transplant in both aGVHD (grade II-III) and cGVHD patients.
Conclusions:
- HSPA1L mRNA expression in whole blood at 28 days post-allo-HSCT shows promise as a predictive biomarker for cGVHD.
- HSPA1B mRNA may also serve as a biomarker for GVHD development after allo-HSCT.
- Further validation in larger cohorts is warranted to confirm the clinical utility of these HSP70 biomarkers.
Abstract:
Graft-versus-host disease (GVHD) can be a fatal complication of allogeneic stem cell transplantation (allo-HSCT). GVHD can be classified as acute (aGVHD: up to 100 days) or chronic (cGVHD: after 100 days) based on the time-point of disease occurrence. At present there are a limited number of biomarkers available for use in the clinic. Thus, the aim of this research was to evaluate the biomarker potential of the extensively studied Heat Shock Protein 70 family members (HSPA1A/HSPA1B and HSPA1L) at the messenger RNA (mRNA) level in acute and cGVHD patient cohorts. In the skin biopsies, HSPA1L mRNA expression was lower in patients with severe aGVHD (grades II-III) when compared to those with none or low grade aGVHD (grades 0-I) and normal controls. In whole blood, HSPA1L mRNA expression level was significantly (p = 0.008) up-regulated at 28 days post-transplant in cGVHD patients with a significant area under the curve (AUC = 0.773). In addition, HSPA1B expression in whole blood was significantly higher at 3 months post-transplant in both the aGVHD grade II-III (p = 0.012) and cGVHD (p = 0.027) patients. Our initial results in this small cohort show that quantifying HSPA1L mRNA expression in the whole blood of allo-HSCT patients at day 28 post-allo-HSCT may be a useful predictive biomarker for cGVHD.
