1.
Significant Associations of IgG Glycan Structures With Chronic Graft-Versus-Host Disease Manifestations: Results of the Cross-Sectional NIH Cohort Study
Prenc, E., Pulanic, D., Pucic-Bakovic, M., Ugrina, I., Desnica, L., Milosevic, M., Pirsl, F., Mitchell, S., Rose, J., Vrhovac, R., et al
Frontiers in immunology. 2021;12:633214
Abstract
Chronic graft-versus-host disease (cGvHD) is a systemic alloimmune and autoimmune disorder and a major late complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). The disease is characterized by an altered homeostasis of the humoral immune response. Immunoglobulin G (IgG) glycoprotein is the main effector molecule of the humoral immune response. Changes in IgG glycosylation are associated with a number of autoimmune diseases. IgG glycosylation analysis was done by the means of liquid chromatography in the National Institutes of Health (NIH) cohort of 213 cGvHD patients. The results showed statistically significant differences with regards to cGvHD NIH joint/fascia and skin score, disease activity and intensity of systemic immunosuppression. ROC analysis confirmed that IgG glycosylation increases specificity and sensitivity of models using laboratory parameters and markers of inflammation associated with cGvHD (eosinophil count, complement components C3 and C4 and inflammation markers: albumin, CRP and thrombocyte count). This research shows that IgG glycosylation may play a significant role in cGvHD pathology. Further research could contribute to the understanding of the disease biology and lead to the clinical biomarker development to allow personalized approaches to chronic GvHD therapy.
2.
The impact of KIR2DS4 gene on clinical outcome after hematopoietic stem cell transplantation
Burek Kamenaric, M., Stingl Jankovic, K., Grubic, Z., Serventi Seiwerth, R., Maskalan, M., Nemet, D., Mikulic, M., Zunec, R.
Human Immunology. 2017;78(2):95-102
Abstract
Killer cell immunoglobulin-like receptors (KIR) are a family of inhibitory/activating receptors expressed on NK cells. Interactions of KIR receptors with KIR ligands have been shown to modify hematopoietic stem cell transplantation (HSCT) outcome. The aim of this research was to determine the KIR2DS4 allele variants distribution among 111 patients with different hematological malignancy who underwent HSCT and their donors, and to evaluate KIR2DS4 alleles' impact on HSCT outcome. The KIR gene frequency analysis showed a significantly higher incidence of full-length KIR2DS4 alleles among patients. The impact of KIR2DS4 alleles on transplantation outcomes revealed that donors' full-length KIR2DS4 alleles is associated with lower overall survival rates, higher risk of GVHD and higher relapse incidence. The expression of full-length KIR2DS4 allele variants may contribute to a worse clinical outcome after HSCT. KIR typing for KIR2DS4 could be used as an additional criterion for selecting suitable donors in cases when more than one HLA identical donor is identified for a specific patient. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
3.
Glycoprotein YKL-40: a novel biomarker of chronic graft-vs-host disease activity and severity?
Durakovic, N., Krecak, I., Peric, Z., Milosevic, M., Desnica, L., Pulanic, D., Pusic, I., Kusec, V., Vrhovac, R., Pavletic, S. Z., et al
Croatian Medical Journal. 2016;57(3):239-46
Abstract
AIM: To investigate whether increased YKL-40 levels positively correlate with graft-vs-host disease (cGVHD) activity and severity and if YKL-40 could serve as a disease biomarker. METHODS This case-control study was conducted at the University Hospital Centre Zagreb from July 2013 to October 2015. 56 patients treated with hematopoietic stem cell transplantation (HSCT) were included: 35 patients with cGVHD and 21 without cGVHD. There was no difference between groups in age, sex, median time from transplant to study enrollment, intensity of conditioning, type of donor, or source of stem cells. Blood samples were collected at study enrollment and YKL-40 levels were measured with ELISA. Disease activity was estimated using Clinician's Impression of Activity and Intensity of Immunosuppression scales and disease severity using Global National Institutes of Health (NIH) score. RESULTS YKL-40 levels were significantly higher in cGVHD patients than in controls (P=0.003). The difference remained significant when patients with myelofibrosis were excluded from the analysis (P=0.017). YKL-40 level significantly positively correlated with disease severity (P<0.001; correlation coefficient 0.455), and activity estimated using Clinician's Impression of Activity (P=0.016; correlation coefficient 0.412) but not using Intensity of Immunosuppression (P=0.085; correlation coefficient 0.296). CONCLUSION YKL-40 could be considered a biomarker of cGVHD severity and activity. However, validation in a larger group of patients is warranted, as well as longitudinal testing of YKL-40 levels in patients at risk of developing cGVHD.