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Published on: October 31, 2012
Plasma CXCL9 elevations correlate with chronic GVHD diagnosis
Carrie L Kitko1, John E Levine, Barry E Storer
1Blood and Marrow Transplant Program, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI;
Insights
Researchers identified CXCL9 as a promising biomarker for chronic graft-versus-host disease (cGVHD). Elevated CXCL9 levels in patients indicate a higher likelihood of developing cGVHD, aiding in early detection and management.
Area of Science:
- Immunology
- Oncology
- Biomarker Discovery
Background:
- Chronic graft-versus-host disease (cGVHD) lacks validated biomarkers for diagnosis.
- Accurate biomarkers are crucial for timely intervention and improved patient outcomes.
Purpose of the Study:
- To identify and validate protein biomarkers for the early detection of de novo-onset chronic GVHD.
- To assess the diagnostic and prognostic value of candidate proteins, particularly CXCL9.
Main Methods:
- Protein microarray and ELISA were used to compare protein expression in cGVHD patients and controls.
- Candidate proteins were validated in independent patient cohorts using plasma concentration analysis.
- Statistical analysis included ROC curves and multivariable regression to assess discriminatory value.
Main Results:
- Five candidate proteins (CXCL9, IL2Rα, elafin, CD13, BAFF) distinguished cGVHD from controls.
- CXCL9 demonstrated the highest discriminatory value (AUC = 0.83).
- Elevated CXCL9 plasma concentrations were significantly associated with higher cGVHD frequency in two independent cohorts, even after adjusting for clinical factors.
Conclusions:
- CXCL9 is a validated and elevated biomarker in patients with newly diagnosed chronic GVHD.
- CXCL9 holds significant potential for early diagnosis and risk stratification of cGVHD.
- Further research may incorporate CXCL9 into clinical diagnostic algorithms for cGVHD.
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.
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