Bilateral Corneal Perforation in a Patient with Chronic Ocular Graft-Versus-Host Disease: A Case Report and Literature Review

Graft-versus-host disease (GVHD) is a serious complication that may occur in patients receiving allogeneic hematopoietic stem cell transplant (HSCT). GVHD occurs because of the immunological reaction between the donor’s T cells and the recipient’s antigens; GVHD may develop in different tissues, including the eye. Corneal perforation is an uncommon but vision-threatening manifestation of GVHD. We reported the case of a 65-year-old male patient who developed corneal perforation sequentially in both eyes 3 years after receiving HSCT. Conservative treatment with topical steroids and lubricants, bandage contact lens, and lacrimal punctal occlusion surgery resulted in the successful resolution of the corneal perforation with satisfactory visual recovery in the right eye. Therefore, corneal perforation can occur as the presenting manifestation of ocular GVHD. Regular ophthalmological examinations are recommended after HSCT to enable the early diagnosis of ocular GVHD and prompt treatment initiation

Maps of open chromatin highlight cell type-restricted patterns of regulatory sequence variation at hematological trait loci

<p>Nearly three-quarters of the 143 genetic signals associated with platelet and erythrocyte phenotypes identified by meta-analyses of genome-wide association (GWA) studies are located at non-protein-coding regions. Here, we assessed the role of candidate regulatory variants associated with cell type-restricted, closely related hematological quantitative traits in biologically relevant hematopoietic cell types. We used formaldehyde-assisted isolation of regulatory elements followed by next-generation sequencing (FAIRE-seq) to map regions of open chromatin in three primary human blood cells of the myeloid lineage. In the precursors of platelets and erythrocytes, as well as in monocytes, we found that open chromatin signatures reflect the corresponding hematopoietic lineages of the studied cell types and associate with the cell type-specific gene expression patterns. Dependent on their signal strength, open chromatin regions showed correlation with promoter and enhancer histone marks, distance to the transcription start site, and ontology classes of nearby genes. Cell type-restricted regions of open chromatin were enriched in sequence variants associated with hematological indices. The majority (63.6%) of such candidate functional variants at platelet quantitative trait loci (QTLs) coincided with binding sites of five transcription factors key in regulating megakaryopoiesis. We experimentally tested 13 candidate regulatory variants at 10 platelet QTLs and found that 10 (76.9%) affected protein binding, suggesting that this is a frequent mechanism by which regulatory variants influence quantitative trait levels. Our findings demonstrate that combining large-scale GWA data with open chromatin profiles of relevant cell types can be a powerful means of dissecting the genetic architecture of closely related quantitative traits.</p>