Evidence map›Paper›PMID 40362547›Full record

ReviewInternational journal of molecular sciences2025

Novel Tear Biomarkers in Ocular Graft Versus Host Disease Associated with Th1/Th2 Immune Responses: A Case Series and Literature Review.

Mihaela-Madalina Timofte-Zorila, Mariana Pavel-Tanasa, Daniela Constantinescu, Corina Cianga, Daniel Constantin Branisteanu, Giuseppe Giannaccare, Filippo Lixi, Angela Dascalescu, Nicoleta Vlas, Sabina Turcas and 1 more

Abstract readCase ReportsReview
In one paragraph

Review in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Trial
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Mihaela-Madalina Timofte-ZorilaFaculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania.
Mariana Pavel-TanasaDepartment of Immunology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania.ORCID 0000-0002-2802-5993
Daniela ConstantinescuDepartment of Immunology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania.ORCID 0000-0003-0732-3745
Corina CiangaDepartment of Immunology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania.
Daniel Constantin BranisteanuFaculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania.ORCID 0009-0009-5147-9596
Giuseppe GiannaccareEye Clinic, Department of Surgical Sciences, University of Cagliari, 09124 Cagliari, Italy.ORCID 0000-0003-2617-0289
Filippo LixiEye Clinic, Department of Surgical Sciences, University of Cagliari, 09124 Cagliari, Italy.ORCID 0009-0008-0956-4925
Angela DascalescuDepartment of Hematology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania.
Nicoleta VlasFaculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania.
Sabina TurcasFaculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania.
Cristina PredaEndocrinology Department, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania.

Funding

Grigore T. Popa University of Medicine and Pharmacy of Iasi doctoral grantRomanian Ministry of Research, Innovation and Digitization, CNCS - UEFISCDI PN-IV-P2-2.1-TE-2023-1182
6 · The paper itself

Abstract

Ocular graft versus host disease (oGVHD) is a common complication of allogeneic hematopoietic stem cell transplantation and may be associated with dry eye disease and chronic inflammation and fibrosis. Immune dysregulation, particularly the Th1/Th2 imbalance, plays a key role in the progression of oGVHD. This case study presents two oGVHD patients (a 20-year-old with acute oGVHD and a 59-year-old with chronic oGVHD), analyzing clinical dry eye parameters (Schirmer test I, tear film break-up time, Ocular Surface Disease Index (OSDI), and kerato-conjunctival staining) alongside tear biomarkers. A 27-plex tear cytokine analysis was performed using the Luminex200 platform, assessing various biomarkers against a control group-defined normal range. Key biomarkers included beta2-microglobulin (β2-MG), complement components, chemokines, growth factors, and both pro-inflammatory and anti-inflammatory cytokines, as well a series of soluble ligand and receptors. The study identified distinct biomarker progression patterns during topical corticosteroid treatment in the acute oGHVD patient, suggesting potential shifts in Th1/Th2 responses as the disease progressed. Notably, the soluble CD27, TNF-related apoptosis-inducing ligand (TRAIL) receptor 2 (TRAIL-R2), chemokine ligand 2 (CCL2), and IL-1β, initially elevated, normalized during treatment, while tear-soluble Fas remained highly elevated (>400-fold). Conversely, soluble TRAIL, which was initially at very low levels (100-fold lower), increased during treatment and reached normal tear levels, coinciding with improvements in the clinical ocular inflammation symptoms and OSDI score. This case study also highlights potential differences between acute and chronic oGVHD, particularly in the distinct patterns of novel tear biomarkers such as CD27, TRAIL/TRAIL-R2, and CCL2. Enhancing our understanding of biomarker dynamics may improve disease monitoring and pave the way for personalized management strategies to improve patient outcomes.

Indexed as

BiomarkersDry Eye SyndromesGraft vs Host DiseaseTearsTh1 CellsTh2 CellsCytokinesHematopoietic Stem Cell TransplantationHumansMaleMiddle AgedYoung AdultBiomarkersCytokinesCD27cytokineseye inflammationFasocular GVHDTRAILTRAIL-R2

Identifiers

PMID40362547
PMCPMC12072947

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.