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The Pathologist / Issues / 2025 / June / Early GVHD Risk Linked to sMICA
Hematology Screening and monitoring Hematology Microbiology and Immunology Clinical care Research and Innovations

Blood Biomarker Identified for Early GVHD Risk

Soluble MICA levels before and during engraftment identified high GVHD risk after stem cell transplant

06/23/2025 News 1 min read

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Credit: Adobe Stock (Edited)

Soluble MHC class I chain-related protein A concentrations above 93.5 pg/mL predicted graft-versus-host disease with 93 percent specificity, according to a recent study.

Researchers identified soluble MHC class I chain-related protein A (sMICA) as a potential biomarker for early detection of graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (HSCT), according to findings published in Frontiers in Medicine. The prospective, single-center study, led by Alexander Kupis of the Medical University of Vienna, enrolled 48 adult patients undergoing HSCT between 2020 and 2021. After excluding four patients who did not engraft or died early, 44 patients were included in the final analysis.

Blood samples were obtained at three time points: before conditioning (pre-transplant), during peri-engraftment, and on day 100 post-transplant. Researchers measured sMICA concentrations using enzyme-linked immunosorbent assays alongside C-reactive protein (CRP) and von Willebrand factor (VWF) as comparators for systemic inflammation and endothelial activation.

Of the 44 patients, 30 developed GVHD, with 16 cases of acute GVHD, eight of chronic GVHD, and six with both. Soluble MICA concentrations were higher at pre-transplant and engraftment in patients who later developed GVHD. The median pre-transplant sMICA level was 33.5 pg/mL. Among those with concentrations above this threshold, 86 percent developed GVHD compared with 50 percent of those below it.

Receiver operating characteristic analysis demonstrated that pre-transplant sMICA had an area under the curve of 0.78 for predicting GVHD. Concentrations above 93.5 pg/mL were associated with 93 percent specificity but only 47 percent sensitivity. Logistic regression analysis showed that the risk of developing GVHD increased incrementally with rising sMICA levels. When grouped categorically, each ascending sMICA group carried more than threefold increased odds of GVHD development.

Importantly, sMICA levels did not correlate with CRP or VWF concentrations and remained unaffected by systemic inflammation, suggesting sMICA is not an acute phase reactant. These findings indicate that sMICA may serve as a specific, inflammation-independent biomarker for identifying patients at elevated risk for GVHD, supporting its potential utility in guiding early surveillance or prophylactic strategies following HSCT. Further validation in larger, multicenter trials is warranted.

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