Ophthalmic manifestations are associated with reduced tear lymphotoxin-\u03b1 levels in chronic ocular graft-versus-host disease

Jiao Ma,Jing Hong,Bohao Hu,Yinghan Zhao,Zhan Shen,Rongmei Peng,Chendi Li

doi:10.1186/s12886-022-02251-y

Jiao Ma, Jing Hong + Show 5 more

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https://doi.org/10.1186/s12886-022-02251-y

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Abstract

PurposeTo determine the role tear lymphotoxin-α (LT-α) in chronic ocular graft-versus-host disease (oGVHD).MethodsTwenty-two chronic oGVHD and 17 control tear samples were collected, and commercial test strips were used to detect LT-α concentrations. Concentration differences between patients with and without oGVHD were determined via Mann-Whitney U test. The correlation between LT-α levels and ophthalmic parameters was analyzed using Spearman’s test.ResultsThe concentration of LT-α was significantly lower in oGVHD patients than in controls. LT-α levels were significantly correlated with OSDI, NIH eye score, T-BUT, and CFS among all participants. ROC analysis revealed that the area under the curve of LT-α was 0.847, and the cutoff value for chronic oGVHD diagnosis was 0.203 ng/mL.ConclusionOur study revealed the significant decrease of tear LT-α in oGVHD, and suggested LT-α as a promising marker for chronic oGVHD diagnosis.

Highlights

Allogeneic hematopoietic stem cell transplantation is a major therapy for many patients with hematological malignances [1]
Chronic ocular GVHD (oGVHD) patients were diagnosed in accordance with the National Institutes of Health (NIH) consensus [5], and inclusion criteria were set as we previously described [16]: (1) NIH eye score ≥ 1 point; (2) ocular surface disease index (OSDI) score > 12 points; (3) corneal fluorescein staining (CFS) ≥ 1; and (4) Schirmer’s test without topical anesthesia ≤5 mm in 5 min
Tear LT‐α concentration The concentration of LT-α in tears was compared between patients with (n = 22) and without chronic oGVHD (n = 17), and interestingly, we observed a significant decrease in LT-α concentration in oGVHD patients (0.093 ± 0.090 ng/mL) compared to that of controls (0.54 ± 2.84 ng/mL)

Summary

Introduction

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a major therapy for many patients with hematological malignances [1]. Chronic graftversus-host disease (GVHD) represents a common complication of allo-HSCT, affecting 30–70% of human leukocyte antigen-matched recipients [2, 3]. As an immune disease involving tissue inflammation and fibrosis, chronic GVHD may lead to permanent dysfunction in multiple organs. The expression of LT-α is restricted to activated CD4+ Th1 and Th17 subsets, CD8+ T cells, B cells, and natural killer cells [11,12,13], all of which are closely implicated in GVHD. Chiang EY et al reported that LT-α expression was upregulated in activated human donor lymphocytes and that targeted depletion of these donor cells

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