Immune Processes and Pathogenic Fibrosis in Ocular Chronic Graft-Versus-Host Disease and Clinical Manifestations after Allogeneic Hematopoietic Stem Cell Transplantation

  title={Immune Processes and Pathogenic Fibrosis in Ocular Chronic Graft-Versus-Host Disease and Clinical Manifestations after Allogeneic Hematopoietic Stem Cell Transplantation},
  author={Yoko Ogawa and Shigeto Shimmura and Murat Doğru and Kazuo Tsubota},
Activation of the immune system and progressive fibrosis are prominent features of chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation. The main histologic findings in affected exocrine glands are marked fibrosis of the interstitium and prominent increase in the number of fibroblasts, accompanied by mild lymphocytic infiltration. Clinically, the severity of dry eye is correlated with the degree of fibrotic changes, rather than with the amount of… 

Senescence‐associated secretory phenotype promotes chronic ocular graft‐vs‐host disease in mice and humans

  • Mio YamaneShinri Sato K. Tsubota
  • Biology, Medicine
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2020
Results in the sclerodermatous cGVHD mouse model suggest that inhibiting the major components of the SASP, including IL‐6 and CXCL9, with senolytics is a potential novel strategy for treating cGV HD‐affected LGs and suggest that targeted senolytic treatment may be a new therapeutic option for this disease.

Tissue Renin–Angiotensin System in Lacrimal Gland Fibrosis in a Murine Model of Chronic Graft-Versus-Host Disease

It is concluded that the tissue RAS is involved in the fibrotic pathogenesis of the lacrima gland and that AT1R blockers have a therapeutic effect on lacrimal gland fibrosis in cGVHD model mice.

In vivo confocal microscopic characterisation of the cornea in chronic graft-versus-host disease related severe dry eye disease

In vivo confocal microscopic findings of the cornea in patients with severe ocular cGvHD include a rarefaction of the sub basal corneal nerve plexus and dense accumulation of hyper-reflective extracellular matrix in the anterior stroma.

Ocular surface system alterations in ocular graft-versus-host disease: all the pieces of the complex puzzle

The purpose of this literature review is to describe all the clinical manifestations occurring in the setting of ocular GVHD, and to further report the outcomes of conventional and novel therapies.

[Non-Invasive Diagnosis of Ocular Graft-versus-Host Disease].

Diagnosis and treatment of ocular GvHD are a challenge for attending ophthalmologists and require intensive interdisciplinary patient care in particular with haemato-oncologists.

Lifitegrast ophthalmic solution for treatment of ocular chronic graft-versus-host disease

The findings of this study suggest lifitegrast is safe, well-tolerated and is an effective option for oGVHD manifesting as KCS, and has the potential to fulfill an unmet need in allogeneic transplant patients with ocular GVHD.

A Single-Center Pilot Prospective Study of Topical Application of Platelet-Derived Eye Drops for Patients with Ocular Chronic Graft-versus-Host Disease.

  • F. ZallioL. Mazzucco M. Ladetto
  • Medicine
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • 2016

[Treatment of chronic posterior blepharitis after allogeneic hematopoietic stem cell transplantation (a case report)].

Normalization of the outflow of meibomian gland secretion after the medical procedure was a prerequisite for improving the quantitative and qualitative composition of the lipid layer of the tear film and a factor contributing to a decrease in the amplitude of inflammation, which is reflected in the clinical and functional results.

International Chronic Ocular Graft-vs-Host-Disease (GVHD) Consensus Group: Proposed Diagnostic Criteria for Chronic GVHD (Part I)

New diagnostic criteria for chronic ocular GVHD are presented by the Consensus Group and Validation studies are needed to identify the best combination of the proposed metrics to maximize diagnostic sensitivity and specificity.



Inflammation and pathogenic fibrosis in human ocular chronic graft versus host disease

This mini-review will focus on recent researches on the immune response and pathogenic fibrosis in human ocular chronic GVHD, in which the lacrimal gland is examined as one of the targeted exocrine glands to help elucidate the pathogenesis of lacrima gland as well as systemic chronic GvHD fibrosis and facilitate the development of novel anti-fibrotic interventions.

Dry Eye as a Major Complication Associated with Chronic Graft-Versus-Host Disease after Hematopoietic Stem Cell Transplantation

It is suggested that periductal fibroblasts are involved in fibrogenic and immune processes by interacting with T cells in the lacrimal gland of patients with chronic GVHD, resulting in rapidly progressive dry eye.

Murine Sclerodermatous Graft-Versus-Host Disease, a Model for Human Scleroderma: Cutaneous Cytokines, Chemokines, and Immune Cell Activation1

The Scl GVHD model is valuable for testing new interventions in early fibrosing diseases, and chemokines may be new potential targets in scleroderma.

Donor fibroblast chimerism in the pathogenic fibrotic lesion of human chronic graft-versus-host disease.

Fibroblasts originating from circulating donor-derived precursors may participate in the excessive fibrosis in patients with chronic GVHD, and the chimeric status of accumulated CD34+ fibroblast in the lacrimal gland of patients with Chronic GV HD is indicated.

Epithelial mesenchymal transition in human ocular chronic graft-versus-host disease.

Findings indicate that ocular cGVHD epithelia gain the mesenchymal phenotype and the capacity to migrate into the subepithelial stroma and suggest that EMT may be partially responsible for the conjunctival and lacrimal gland fibrosis found in patients with cGV HD.

Lacrimal gland involvement in graft-versus-host disease: a murine model.

This study describes the first murine model of lacrimal gland GVHD with features that closely mimic those described in human disease and indicates that Lacrimal involvement occurs in acute GV HD.

Biology of chronic graft-versus-host disease: implications for a future therapeutic approach.

Recommendations of the NIH Consensus Development Project on Criteria for Clinical Trials in Chronic GVHD have begun to standardize the diagnosis and clinical assessment of the disease and suggest multiple biological mechanisms account for the diverse features the disease.

Update on ocular graft versus host disease

  • Stella K. Kim
  • Medicine, Biology
    Current opinion in ophthalmology
  • 2006
Ocular graft versus host disease evaluation, diagnosis, and management should be approached in a multidisciplinary fashion in the context of the patient's overall graft vs host disease status.

Bone marrow-derived progenitor cells in pulmonary fibrosis.

The collagen-producing lung fibroblasts in pulmonary fibrosis can also be derived from BM progenitor cells, as shown in mice durably engrafted with BM isolated from transgenic mice expressing enhanced GFP.

Periductal area as the primary site for T-cell activation in lacrimal gland chronic graft-versus-host disease.

The results strongly suggest that CD4(+) and CD8(+) T cells in the lacrimal glands of patients with cGVHD are primarily activated in the periductal area through antigenic stimulation by potent antigen-presenting cells and stromal fibroblasts, and exert various effector functions, including cytotoxic effects on glandular epithelial cells.