TY - JOUR
T1 - Chronic active T cell–mediated rejection is variably responsive to immunosuppressive therapy
AU - Kung, Vanderlene L.
AU - Sandhu, Rana
AU - Haas, Mark
AU - Huang, Edmund
N1 - Funding Information:
This work was funded by the Cedars-Sinai CSRI-Academic Pathology Award for Basic, Translational and Clinical Research. We thank Lin Li and Warren Tourtellotte for generous use of laboratory space and equipment.
Publisher Copyright:
© 2021 International Society of Nephrology
PY - 2021/8
Y1 - 2021/8
N2 - Chronic active T cell–mediated rejection (CA TCMR) is a newly described variant of kidney allograft rejection associated with long-term graft loss. Whether this form of rejection is related to under immunosuppression is debated and the benefit of immunosuppressive therapy in CA TCMR is unknown. Here we investigate the amenability of CA TCMR to treatment and examine the impact of clinical, histologic, and molecular parameters on outcomes. In a retrospective single institution review, we identified 48 cases of isolated CA TCMR, of which 44 were treated with pulse steroids or anti-thymocyte globulin, or both. Defining treatment response as an at least 50% estimated glomerular filtration rate recovery, a response was achieved in 20% of cases at four weeks post initiation of immunosuppressive therapy. Treatment responsiveness did not reflect the presence of concomitant acute T cell–mediated rejection, and was not significantly different between cases with mild, moderate, and severe parenchymal scarring. Although not statistically significant, there was a trend toward greater treatment responsiveness in cases with moderate as opposed to severe tubulitis. By targeted transcriptional profiling, increased allograft mast cells and alterations in lipid metabolism were identified as possible features of treatment resistant CA TCMR. Thus, our study shows that although its prognosis is generally poor, CA TCMR is not a homogenous entity and in a subset of cases, improvement in kidney function can be achieved with immunosuppressive therapy.
AB - Chronic active T cell–mediated rejection (CA TCMR) is a newly described variant of kidney allograft rejection associated with long-term graft loss. Whether this form of rejection is related to under immunosuppression is debated and the benefit of immunosuppressive therapy in CA TCMR is unknown. Here we investigate the amenability of CA TCMR to treatment and examine the impact of clinical, histologic, and molecular parameters on outcomes. In a retrospective single institution review, we identified 48 cases of isolated CA TCMR, of which 44 were treated with pulse steroids or anti-thymocyte globulin, or both. Defining treatment response as an at least 50% estimated glomerular filtration rate recovery, a response was achieved in 20% of cases at four weeks post initiation of immunosuppressive therapy. Treatment responsiveness did not reflect the presence of concomitant acute T cell–mediated rejection, and was not significantly different between cases with mild, moderate, and severe parenchymal scarring. Although not statistically significant, there was a trend toward greater treatment responsiveness in cases with moderate as opposed to severe tubulitis. By targeted transcriptional profiling, increased allograft mast cells and alterations in lipid metabolism were identified as possible features of treatment resistant CA TCMR. Thus, our study shows that although its prognosis is generally poor, CA TCMR is not a homogenous entity and in a subset of cases, improvement in kidney function can be achieved with immunosuppressive therapy.
KW - Banff classification
KW - T cell–mediated rejection
KW - chronic rejection
KW - kidney allograft
KW - mast cells
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U2 - 10.1016/j.kint.2021.03.027
DO - 10.1016/j.kint.2021.03.027
M3 - Article
C2 - 33838162
AN - SCOPUS:85105338501
SN - 0085-2538
VL - 100
SP - 391
EP - 400
JO - Kidney International
JF - Kidney International
IS - 2
ER -