title: Do NK cells contribute to the pathophysiology of transplant-associated thrombotic microangiopathy?
abstract: Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication caused by the aggregation of platelets exposed to the thrombogenic subendothelial matrix of injured endothelial cells. Here, we present a case of a patient transplanted for idiopathic aplastic anemia with a T-cell depleted hematopoietic stem cell graft from an HLA-C mismatched unrelated donor. At day 7 posttransplant, she suffered from acute renal failure with hematuria. The presence of numerous schistocytes, an increased level of lactate dehydrogenase and a renal biopsy with multiple vascular injuries confirmed the diagnosis of severe TA-TMA. At day 14, she developed graft versus host disease and died 7 months posttransplantation of multiorgan failure. At day 15, we observed a sizable population of natural killer (NK) cells in the peripheral blood, the number of which reached 0.8 G/L at 4 months posttransplant. Most NK cells lacked inhibitory killer immunoglobulin-like receptors (KIR) specific for the KIR-ligands expressed in the patient. NK cells were also abundantly present in pericardial and pleural fluids and had invaded the kidney, where they colocalized with the renal vasculopathy. Because there are several mechanisms through which NK cells and platelets can activate each other reciprocally, it is conceivable that NK cells contribute to TA-TMA and its progression.
authors.affiliation: Department of Pediatrics, University Hospital of Geneva, Switzerland. marc.ansari@hcuge.ch
authors.forename: M
authors.initials: M
authors.lastname: Ansari
authors.forename: M
authors.initials: M
authors.lastname: Vukicevic
authors.forename: A L
authors.initials: AL
authors.lastname: Rougemont
authors.forename: S
authors.initials: S
authors.lastname: Moll
authors.forename: P
authors.initials: P
authors.lastname: Parvex
authors.forename: F
authors.initials: F
authors.lastname: Gumy-Pause
authors.forename: Y
authors.initials: Y
authors.lastname: Chalandon
authors.forename: J
authors.initials: J
authors.lastname: Passweg
authors.forename: H
authors.initials: H
authors.lastname: Ozsahin
authors.forename: E
authors.initials: E
authors.lastname: Roosnek
mesh_terms: D000741:Anemia, Aplastic / Q000601:surgery*; D002648:Child; D017809:Fatal Outcome; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D057049:Thrombotic Microangiopathies / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology