title: Soluble interleukin-2 receptor concentration as a biochemical indicator for acute graft-versus-host disease after allogeneic bone marrow transplantation.
abstract: When interleukin-2 (IL-2) binds to the IL-2 receptor (IL2-R) on activated T cells, a soluble portion of the receptor (sIL2-R) is released. After allogeneic bone marrow transplantation (BMT), the serum concentration of sIL2-R may, therefore, be a useful surrogate marker for T cell activation that results in acute graft-versus-host disease (aGVHD). To determine if the sIL2-R concentration is a useful marker to help establish a diagnosis of aGVHD, serial sIL2-R concentrations were measured weekly for 4 weeks in 43 patients after allogeneic BMT. Grafts were from HLA-matched siblings (n = 33), 5/6 HLA-matched siblings (n = 3) or matched unrelated donors (n = 7). GVHD prophylaxis included cyclosporine A (CSA)/methotrexate (MTX) (n = 25), solumedrol/CSA (n = 15), or T cell depletion (n = 3). Twenty-three patients developed aGVHD (Grade I, 7; Grade II, 12; Grade III, 4) a median of 28 days after transplant. There was a significant association between a clinical diagnosis of aGVHD and an increase in the sIL2-R concentration (p < 0.001). The mean percent increase (+/-SE) over baseline for patients with a clinical diagnosis of aGVHD was 294% (+/-57%) by week 2 (n = 12), 431% (+/-116%) by week 3 (n = 14), and 650% (+/-315%) by week 4 (n = 9) after BMT. For each 100% increase over baseline, the likelihood of having aGVHD increased by 18%. Six of 20 patients without aGVHD became critically ill and exhibited marked increases in sIL2-R concentrations, similar to patients with a clinical diagnosis of aGVHD who never became critically ill. Fourteen patients without aGVHD who did not become critically ill exhibited negligible increases of sIL2-R in 2- to 4-week period after BMT. These data suggest that serial measurements sIL2-R concentration are helpful in establishing the diagnosis of aGVHD, but are not useful in the most acutely ill patients.
authors.affiliation: Department of Medicine, University of Pennsylvania Medical Center, Philadelphia 19104, USA.
authors.forename: C
authors.initials: C
authors.lastname: Mathias
authors.forename: R
authors.initials: R
authors.lastname: Mick
authors.forename: S
authors.initials: S
authors.lastname: Grupp
authors.forename: K
authors.initials: K
authors.lastname: Duffy
authors.forename: F
authors.initials: F
authors.lastname: Harris
authors.forename: G
authors.initials: G
authors.lastname: Laport
authors.forename: E
authors.initials: E
authors.lastname: Stadtmauer
authors.forename: S
authors.initials: S
authors.lastname: Luger
authors.forename: S
authors.initials: S
authors.lastname: Schuster
authors.forename: M A
authors.initials: MA
authors.lastname: Wasik
authors.forename: D L
authors.initials: DL
authors.lastname: Porter
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003422:Critical Care; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood* / Q000175:diagnosis; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D011237:Predictive Value of Tests; D012372:ROC Curve; D015375:Receptors, Interleukin-2 / Q000097:blood*; D012680:Sensitivity and Specificity; D012995:Solubility; D013997:Time Factors; D014184:Transplantation, Homologous / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D015375:Receptors, Interleukin-2