Discovery of Biomarkers for Chronic Graft-versus-Host Disease
To the Editor:
We read the article by Dogan and colleagues1 regarding the cardiac effects of chronic graft-versus-host disease (cGVHD) in patients who had undergone allogeneic stem cell transplantation. Chronic GVHD is a severe complication after allogeneic bone marrow transplantation, which is an immunotherapeutic option in several hematologic diseases.
Although the pathogenesis of cGVHD remains unclear, it is solidly linked to graft-versus-leukemia (GVL) reactions; the balance between GVHD and the beneficial GVL-effect anticancer capacity of donor immune cells is crucial to the outcome of transplantation. Several variables have been observed clinically, such as the type of disease, the conditioning regimen, and relevant polymorphisms of the genes that might contribute to interpatient variability in alloimmune responses.
Investigators in Spain have found that the cytotoxic T-lymphocyte antigen 4 (CTLA-4) CT60 AA genotype is associated with an increased risk of relapse and a higher transplant-related mortality rate.2 In addition, investigators have proposed that the major histocompatibility complex class I chain-related protein A (MICA) is a genetic marker of cGVHD: MICA is a molecule of particular interest because of its participation in non-T-cell receptor-mediated immune function. In particular, Boukouaci and colleagues3 have found that the presence of MICA-129 values increases the risk of cGVHD in an allele dose-dependent manner. Unfortunately, it is unclear how to use these genetic markers as candidate biomarkers for cGVHD in the clinical setting.
We agree that high-sensitivity C-reactive protein (hs-CRP) is a useful biomarker in patients in whom cGVHD develops after bone marrow transplantation.4 Other investigators have studied the tissue damage caused by the conditioning regimen, infections, and allogeneic immune reactions accompanying the initial elevation of hs-CRP levels during the course of allogeneic hematopoietic stem cell transplantation.5 These findings indicate the possible association of hs-CRP values with the substantial increase in tissue damage that leads to GVHD.5 However, results of a recent study6 show that cGVHD has no impact on cardiovascular risk and that hs-CRP (which is usually considered to be an important biomarker that predicts the risk of cardiovascular events) does not correlate with profiles of high cardiovascular risk. Hence, does hs-CRP exert a direct cardiac effect through an increase in left ventricular mass, or is it a surrogate biomarker only for cGVHD patients? Future efforts in biomarker discovery and consequent validation are needed for an understanding of the pathogenesis of cGVHD.
