Significant Associations of IgG Glycan Structures With Chronic Graft-Versus-Host Disease Manifestations: Results of the Cross-Sectional NIH Cohort Study.

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.

Joint and fascial chronic graft-vs-host disease: correlations with clinical and laboratory parameters.

AIM: To determine if there are correlations between joint and fascial chronic graft-vs-host disease (cGVHD) with clinical findings, laboratory parameters, and measures of functional capacity. METHODS: 29 patients were diagnosed with cGVHD based on National Institutes of Health (NIH) Consensus Criteria at the University Hospital Centre Zagreb from October 2013 to October 2015. Physical examination, including functional measures such as 2-minute walk test and hand grip strength, as well as laboratory tests were performed. The relationship between these evaluations and the severity of joint and fascial cGVHD was tested by logistical regression analysis. RESULTS: 12 of 29 patients (41.3%) had joint and fascial cGVHD diagnosed according to NIH Consensus Criteria. There was a significant positive correlation of joint and fascial cGVHD and skin cGVHD (P<0.001), serum C3 complement level (P=0.045), and leukocytes (P=0.032). There was a significant negative correlation between 2-minute walk test (P=0.016), percentage of cytotoxic T cells CD3+/CD8+ (P=0.022), serum albumin (P=0.047), and Karnofsky score (P<0.001). Binary logistic regression model found that a significant predictor for joint and fascial cGVHD was cGVHD skin involvement (odds ratio, 7.79; 95 confidence interval 1.87-32.56; P=0.005). CONCLUSION: Joint and fascial cGVHD manifestations correlated with multiple laboratory measurements, clinical features, and cGVHD skin involvement, which was a significant predictor for joint and fascial cGVHD.

Which questionnaires should we use to evaluate quality of life in patients with chronic graft-vs-host disease?

AIM: To investigate the ability of two standard quality of life (QOL) questionnaires - The Short Form (36-item) Health Survey (SF-36) and The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ C30) to evaluate QOL in patients with chronic graft-vs-host disease (cGVHD) graded according to National Institutes of Health (NIH) consensus criteria. METHODS: In this cross-sectional study, QOL was assessed in patients who underwent allogeneic stem cell transplantation (allo-SCT) at the University Hospital Centre Zagreb and were alive and in complete remission for more than one year after allo-SCT. RESULTS: The study included 58 patients, 38 patients with cGVHD and 20 controls, patients without cGVHD. Patients with cGVHD scored according to the NIH criteria had significantly lower scores of global health status and lower QOL on all SF-36 subscales and most of QLQ C30 functional subscales (P<0.050 for all comparisons). Furthermore, patients with active cGVHD had significantly lower QOL scores than patients with inactive cGVHD, and this difference was most evident in physical functioning subscale of SF-36 (P=0.0007) and social functioning subscale of QLQ C30 (P=0.009). CONCLUSION: cGVHD scored according to the NIH criteria is correlated with patient-reported QOL, particularly in the physical domains as detected by SF-36. QLQ C30 questionnaire adds more information on social functioning and should be used as a valuable tool in the evaluation of social domains in cGVHD patients.

Potential of glycosylation research in graft versus host disease after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Glycans, complex oligosaccharides, are directly involved in almost every biological process, have a fundamental role in the immune system, and are probably involved in nearly every human disease. However, glycosylation has been greatly ignored in the area of allogeneic hematopoietic stem cell transplantation (alloHSCT) and graft versus host disease (GVHD). Both acute and chronic GVHD are multisystemic debilitating immunological disturbances arising after alloHSCT. SCOPE OF REVIEW: In this paper, we review the glycosylation research already done in the field of alloHSCT and GVHD and evaluate further potential of glycan analysis in GVHD by looking into resembling inflammatory and autoimmune conditions. MAJOR CONCLUSIONS: Glycan research could bring significant improvement in alloHSCT procedure with reduction in following complications, such as GVHD. Identifying glycan patterns that induce self-tolerance and the ones that cause the auto- and allo-immune response could lead to innovative and tissue-specific immunomodulative therapy instead of the current immunosuppressive treatment, enabling preservation of the graft-versus-tumor effect. Moreover, improved glycan pattern analyses could offer a more complete assessment and greatly needed dynamic biomarkers for GVHD. GENERAL SIGNIFICANCE: This review is written with a goal to encourage glycan research in the field of alloHSCT and GVHD as a perspective tool leading to improved engraftment, discovery of much needed biomarkers for GVHD, enabling an appropriate therapy and improved monitoring of therapeutic response. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc.