title: Plasma CXCL9 elevations correlate with chronic GVHD diagnosis.
abstract: There are no validated biomarkers for chronic GVHD (cGVHD). We used a protein microarray and subsequent sequential enzyme-linked immunosorbent assay to compare 17 patients with treatment-refractory de novo-onset cGVHD and 18 time-matched control patients without acute or chronic GVHD to identify 5 candidate proteins that distinguished cGVHD from no cGVHD: CXCL9, IL2Rα, elafin, CD13, and BAFF. We then assessed the discriminatory value of each protein individually and in composite panels in a validation cohort (n = 109). CXCL9 was found to have the highest discriminatory value with an area under the receiver operating characteristic curve of 0.83 (95% confidence interval, 0.74-0.91). CXCL9 plasma concentrations above the median were associated with a higher frequency of cGVHD even after adjustment for other factors related to developing cGVHD including age, diagnosis, donor source, and degree of HLA matching (71% vs 20%; P < .001). A separate validation cohort from a different transplant center (n = 211) confirmed that CXCL9 plasma concentrations above the median were associated with more frequent newly diagnosed cGVHD after adjusting for the aforementioned factors (84% vs 60%; P = .001). Our results confirm that CXCL9 is elevated in patients with newly diagnosed cGVHD.
authors.affiliation: Blood and Marrow Transplant Program, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI;
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Kitko
authors.forename: John E
authors.initials: JE
authors.lastname: Levine
authors.forename: Barry E
authors.initials: BE
authors.lastname: Storer
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Chai
authors.forename: David A
authors.initials: DA
authors.lastname: Fox
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Braun
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Couriel
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Martin
authors.forename: Mary E
authors.initials: ME
authors.lastname: Flowers
authors.forename: John A
authors.initials: JA
authors.lastname: Hansen
authors.forename: Lawrence
authors.initials: L
authors.lastname: Chang
authors.forename: Megan
authors.initials: M
authors.lastname: Conlon
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Fiema
authors.forename: Rachel
authors.initials: R
authors.lastname: Morgan
authors.forename: Prae
authors.initials: P
authors.lastname: Pongtornpipat
authors.forename: Kelly
authors.initials: K
authors.lastname: Lamiman
authors.forename: James L M
authors.initials: JL
authors.lastname: Ferrara
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Sophie
authors.initials: S
authors.lastname: Paczesny
mesh_terms: D000328:Adult; D054370:Chemokine CXCL9 / Q000097:blood*; D002908:Chronic Disease; D006086:Graft vs Host Disease / Q000097:blood* / Q000175:diagnosis; D006801:Humans; D007165:Immunosuppression Therapy; D008875:Middle Aged
chemical_list: D054370:Chemokine CXCL9