Plasma CXCL9 elevations correlate with chronic GVHD diagnosis

• Published in: Blood 2014-01, Vol.123 (5), p.786-793
• Main Authors: Kitko, Carrie L., Levine, John E., Storer, Barry E., Chai, Xiaoyu, Fox, David A., Braun, Thomas M., Couriel, Daniel R., Martin, Paul J., Flowers, Mary E., Hansen, John A., Chang, Lawrence, Conlon, Megan, Fiema, Bryan J., Morgan, Rachel, Pongtornpipat, Prae, Lamiman, Kelly, Ferrara, James L.M., Lee, Stephanie J., Paczesny, Sophie
• Format: Article
• Language: English
• Subjects: Adult; Chemokine CXCL9 - blood; Chronic Disease; Graft vs Host Disease - blood; Graft vs Host Disease - diagnosis; Humans; Immunosuppression; Middle Aged; Transplantation
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2013-08-520072

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. •Plasma concentrations of CXCL9 are elevated at the onset of cGVHD diagnosis, but not in patients with cGVHD for more than 3 months.•Plasma concentrations of CXCL9 are impacted by immunosuppressive therapy.