17910 Using clonality of T-cell repertoire to distinguish between drug hypersensitivity reaction and acute graft-versus-host disease

Abstract

Graft-versus-host disease (GVHD) is a serious complication of hematopoietic stem cell transplantation, which often leads to morbidity and mortality if not diagnosed and treated early. Acute GVHD is characterized by a clinical triad of cutaneous eruptions, gastrointestinal dysfunction, and liver abnormalities. Cutaneous manifestations of acute GVHD frequently appear before symptoms of other organ systems, but the clinical and histologic features are similar to those of acute morbilliform drug eruption, thus generating a major diagnostic pitfall. Previous studies attempted to define microscopic features of acute GVHD, but these features were later found to be non-specific. We hypothesize that GVHD is mediated by clonal amplification of T-cell repertoire, and therefore can be distinguished from drug hypersensitivity reaction (DHR) by the presence of dominant T-cell receptor clones. To test this hypothesis, we performed “immunosequencing” of T-cell receptors in ten patients with acute GVHD and seven patients with DHR. We calculated the clonality of T-cell repertoire by using normalized Shannon entropy, and found that GVHD patients had significantly higher clonality than DHR patients (P value = 0.05). When a numeric cutoff of clonality alone was used to distinguish GVHD from DHR, a receiver operating characteristic curve had an area under the curve of 0.77. Using a clonality cutoff of 0.042 resulted in sensitivity of 60% and specificity of 71%. Although further validation studies may be required, these results suggested that clonality of T-cell repertoire may be used to distinguish GVHD from DHR in combination of other clinical features.