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4929 Clinical Study on Cytokines Panel in the Diagnosis of Ocular Chronic Graft-Versus-Host Disease

Program: Oral and Poster Abstracts
Session: 722. Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Poster III
Hematology Disease Topics & Pathways:
Research, clinical trials, adult, Clinical Research, Technology and Procedures, Study Population, Human, Animal model, Serologic Tests
Monday, December 11, 2023, 6:00 PM-8:00 PM

Xianjing Cheng, MPH1*, Rui Ji, PhD student1*, Ruihao Huang, PhD student2*, Shiqin Huang, MPH1*, Wei Fan, MPH3*, Yuancheng Zhao, MPH3*, Rongdi Yuan, MD, PhD3*, Xiaoqi Wang, MD2* and Xi Zhang, PhD2

1Medical Center of Hematology, Xinqiao Hospital, Chongqing, China
2Army medical University affiliated Xinqiao Hospital, Chongqing, China
3Department of Ophthalmology, Xinqiao Hospital, Chongqing, China


Chronic graft-versus-host disease (cGVHD) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), affecting 30–70% of patients after allo-HSCT. Sixty to ninety percent of cGVHD patients suffer from ocular chronic GVHD (ocGVHD), which is characterized by new-onset dry, "gritty", or painful eyes, cicatricial conjunctivitis, keratoconjunctivitis sicca, and confluent areas of punctate keratopathy, significantly affecting patients’ quality of life. Nevertheless, the clinical diagnosis of ocGVHD relies heavily on observing symptoms and clinical signs. Treatment is typically initiated during the symptomatic stage, by which time the damage to the ocular tissues may be irreversible. Consequently, it is crucial to investigate methods of early diagnosis for early intervention.


The cGVHD mouse model was established to explore the correlation between cGVHD and serum cytokines. Based on the findings from animal experiments and literature review, a panel of 16 cytokine combinations was identified. Enzyme-linked immunosorbent assay (ELISA) was employed to compare the levels of cytokines in serum and tear samples obtained from patients who underwent allogeneic hematopoietic stem cell transplantation. The inclusion criteria were set as post-allo-HSCT patients between the ages of 18 and 60 who were willing to participate in the study. The visual acuity, ocular pressure, Ocular Surface Disease Index (OSDI) score, Schirmer's test without anesthesia, corneal fluorescein staining (CFS), and fluorescein tear breakup time (FTBUT) were evaluated. The tear sample was collected via Schirmer’s strips. Qualitative data were compared with the chi-square test. The Spearman test was used to analyze correlations (ChiCTR2200062516).


In comparison to the control group, cGVHD mice exhibited elevated concentrations of serum IL-1β, IL-6, IL-8, IL-17, IFN-γ, CX3CL1, CXCL11, CXCL13, CCL11, and CCL19 (P<0.05). A total of 26 post-allo-HSCT ocGVHD patients (38±11y; range 19-57y) and 27 patients without ocGVHD (34±9y; range 20-52y) were recruited. Between patients with and without ocGVHD, there were significant differences in ocular surface parameters (p<0.0001). Analysis of serum and tear cytokine profiles in patients revealed that, when compared to patients without ocular cGVHD, those with ocular cGVHD exhibited increased serum IL-8 levels (P=0.0319, AUC value=0.678), decreased serum IL-10 levels (P=0.0305, AUC value=0.701), elevated tear fluid levels of IL-8, IFN-γ, CXCL9, and CCL17, and lower tear fluid levels of IL-10 and CCL19 (P<0.05, AUC values were >0.7). Moreover, the correlation analysis between tear cytokine levels and ophthalmic indices showed that 3 cytokines were correlated with ophthalmic indices: IL-10, IFN-γ and CXCL9, indicating the superior diagnostic capabilities and correlation with ocGVHD severity. (Figure 1)


Tear fluid demonstrates greater specificity and sensitivity as biomarkers for diagnosing ocular cGVHD compared to serum biomarkers. Among the identified tear cytokines, IL-8, IL-10, IFN-γ, CXCL9, CCL17, and CCL19 can serve as diagnostic biomarkers for ocular cGVHD post-transplantation offering practical reference value for diagnosis. IL-10, IFN-γ and CXCL9 levels could evaluate the severity of ocGVHD. In addition, large-scale prospective studies are warranted to confirm our findings.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH