Abstract

Purpose Heart transplant patients require close follow-up with endomyocardial biopsies, which is the gold standard. Acute cellular rejection (ACR) in endomyocardial biopsies is graded using ISHLT criteria (1990, 2005). The role of mast cells is not very well studied in ACR; results of experimental murine models are ambiguous. To our knowledge, there are no studies specifically analyzing mast cells in ACR for human cardiac transplantation. In our study, we aimed to show whether or not mast cell infiltrates can be used to differentiate low from high grade ACR. Methods This single-institution retrospective study included 42 cases of grade 2/1R (ISHLT 1990/2005) and higher grades of ACR between 2/2016 and 9/2018. 8 cases of ISHLT grade 0 were also examined to serve as a control set. All cases were divided into 3 groups (Table). Mast cells were identified and counted using CD117 immunohistochemistry at 400x magnification. Total mast cell count per biopsy as well as average number of mast cell per fragment (defined by 2mm square) were evaluated. ANOVA and post hoc analysis were performed. Results Biopsies with any ACR showed statistically higher mast cells when compared to negative biopsies. A one way between subjects ANOVA of the three groups was performed and showed a statistically significant difference (p=0.0007). Post hoc analysis utilizing the Tukey-Kramer test revealed a statistically significant difference between grades 3a/3b and grade 0 (q=5.81) and grade 2 and grade 0 (q=3.73). Although grades 3a/3b showed higher average and total number of mast cells when compared to grade 2 ACR, this was not statistically significant. Conclusion Our results show that the total and average number of mast cells per fragment in higher grades of ACR (3a,3b, 2) are significantly higher than grade 0 ACR. The average number of mast cells between grades 3a/3b and grade 2 was not statistically significant. Overall, these results show that mast cells may play an active role in higher stages of acute cellular rejection.

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