AT1R Activating Autoantibodies in Hematopoietic Stem Cell Transplantation

Kathryn L Bradford; Meghan Pearl; Donald B Kohn; Patricia Weng; Ora Yadin; La Vette Bowles; Satiro N De Oliveira; Theodore B Moore

doi:10.1016/j.bbmt.2020.07.029

AT1R Activating Autoantibodies in Hematopoietic Stem Cell Transplantation

Biol Blood Marrow Transplant. 2020 Nov;26(11):2061-2067. doi: 10.1016/j.bbmt.2020.07.029. Epub 2020 Jul 28.

Authors

Kathryn L Bradford¹, Meghan Pearl², Donald B Kohn³, Patricia Weng², Ora Yadin², La Vette Bowles⁴, Satiro N De Oliveira⁵, Theodore B Moore⁶

Affiliations

¹ Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of California, Los Angeles, Los Angeles, California.
² Department of Pediatrics, Division of Pediatric Nephrology, University of California, Los Angeles, Los Angeles, California.
³ Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of California, Los Angeles, Los Angeles, California; Department of Molecular & Medical Pharmacology, University of California, Los Angeles, Los Angeles, California; The Eli & Edythe Broad Stem Cell Research Center, University of California, Los Angeles, Los Angeles, California; Pediatric Blood and Marrow Transplant Program, University of California, Los Angeles, Los Angeles, California.
⁴ Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of California, Los Angeles, Los Angeles, California; Pediatric Blood and Marrow Transplant Program, University of California, Los Angeles, Los Angeles, California.
⁵ Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of California, Los Angeles, Los Angeles, California; The Eli & Edythe Broad Stem Cell Research Center, University of California, Los Angeles, Los Angeles, California; Pediatric Blood and Marrow Transplant Program, University of California, Los Angeles, Los Angeles, California.
⁶ Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of California, Los Angeles, Los Angeles, California; Pediatric Blood and Marrow Transplant Program, University of California, Los Angeles, Los Angeles, California. Electronic address: tbmoore@mednet.ucla.edu.

Abstract

Angiotensin II type 1 receptor activating autoantibodies (AT1R-AAs) have gained attention in solid organ transplant as non-HLA antibodies associated with rejection, vasculopathy, and graft dysfunction. These antibodies have also been reported in the context of pre-eclampsia, scleroderma, and isolated hypertension. Here, we present 3 post-hematopoietic stem cell transplant (HSCT) cases with patients demonstrating elevated levels of AT1R-AAs detected within the first year post-HSCT. All patients had hypertension, and 2 patients exhibited profound diarrhea and hypokalemia. The hypertension, in all cases, was refractory to multiple classes of antihypertensives. Upon autoantibody identification, an angiotensin receptor blocker, losartan, was promptly initiated, and all patients showed blood pressure improvement. The 2 patients with electrolyte disturbances had rapid normalization of these levels and resolution of the diarrhea. These cases demonstrate a previously unreported association of elevated AT1R-AA levels in post-HSCT patients with a rapid response to angiotensin receptor blockade initiation.

Keywords: AT1R activating autoantibodies; Autoimmunity; Hematopoietic stem cell transplantation; Hypertension; Immune dysregulation; Intestinal graft-versus-host disease.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Autoantibodies
Blood Pressure
Graft Rejection
Hematopoietic Stem Cell Transplantation*
Humans
Hypertension*
Receptor, Angiotensin, Type 1

Substances

Autoantibodies
Receptor, Angiotensin, Type 1

Abstract

Publication types

MeSH terms

Substances

Grants and funding