It may lead to an increased risk of a sensitization to corneal antigens and an autoimmune reaction against antigens expressed in corneal tissues. HLA association
Like most autoimmune diseases, Moorens ulcer is thought to be associated with specific HLA haplotypes. In some studies, HLA-DR17 and HLA-DQ2 have been found in increased frequencies in affected patients compared to healthy controls. These results propose a possible association between HLA and Moorens ulcer. Pathology
The precise pathophysiological mechanism of Moorens ulcer remains unclear, but most data suggest that both cell-mediated immunity and humoral immunity are involved in the pathogenesis of the disease.Reduces numbers of suppressor T cells have been found in peripheral blood from patients with Moorens ulcer. This deficit in systematic immunoregulatory mechanism may lead to loss of a control over autoreactive T and B cells and contributes to disease pathogenesis.Immunohistochemical studies in patients suffered from Moorens ulcer showed massive infiltration of multiple types of inflammatory cells in the conjunctival tissue. The cell types in the inflammatory lesion includes CD4+ and CD8+ T-lymphocytes, B-lymphocytes, macrophages, a small amount of neutrophils was also observed in the conjunctiva from patients with Moorens ulcer.In addition, circulating IgG antibodies with specificity for corneal and conjunctival antigens have been isolated from patients with Mooren’s ulcer. Gottsch and colleagues have suggested that calgranulin C, a protein expressed in the corneal stroma, may be a possible main target for autoimmune response causing Mooren’s ulcer.Also, significantly increased expression levels of adhesion and co-stimulatory molecules have been found in ocular tissues affected by Moorens ulcer compared to healthy eyes.
In a 2016 report using both mouse models and a limited human clinical trial ROCK2 inhibition with belumosudil targeted both the immunologic and fibrotic components of cGvHD and reversed the symptoms of the disease.In October 2017, belumosudil was granted orphan drug status in the United States for treatment of patients with cGvHD.Efficacy of belumosudil was evaluated in clinical trial NCT03640481, a randomized, open-label, multicenter dose-ranging trial that included 65 patients with chronic GVHD who were treated with belumosudil 200 mg taken orally once daily.On 16 July 2021, the U.S. Food and Drug Administration (FDA) approved belumosudil for adult and pediatric patients 12 years and older with chronic graft-versus-host disease (chronic GVHD) after failure of at least two prior lines of systemic therapy. Research
IPF is a progressive fibrotic disease where the lining of the lungs become thickened and scarred. Increased ROCK activity has been found in the lungs of humans and animals with IPF. Treatment with belumosudil reduced lung fibrosis in a bleomycin mouse model study.Psoriasis is an inflammatory skin condition where patients experiences eruptions and remissions of thickened, erythematous, and scaly patches of skin. Down-regulation of pro-inflammatory responses was observed with KD025 treatment in Phase 2 clinical studies in patients with moderate to severe psoriasis. References
External links
"Belumosudil". Drug Information Portal. U.S. National Library of Medicine.