N-glikozilacija imunoglobulina G u kroničnoj bolesti presatka protiv primatelja nakon presadbe alogeničnih matičnih krvotvornih stanica [N-glycosylation of immunoglobulin G in chronic graft-versus-host disease]

Chronic graft-versus-host disease (cGvHD) is a systemic alloimmune and autoimmune disorder and the major late complication and leading cause of non-relapse morbidity and mortality after 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 on two populations, American (213 cGvHD patients) and Croatian (30 cGvHD patients and 30 controls (after alloHSCT, without cGvHD)). The American population results showed significant correlation with 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. The Croatian logistic regression model built using glycan and laboratory parameters singled out glycopeptides for which it is justified to assume that they significantly contribute to the cGvHD discrimination. This study has shown that IgG glycosylation plays a significant role in cGvHD pathology, and that further research could contribute to the understanding of the disease biology and lead to the necessary biomarker of chronic GVHD

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

N-glycosylation of immunoglobulin G in chronic graft-versus-host disease

Kronična bolest presatka protiv primatelja (eng. chronic graft-versus-host disease, cGvHD) je sistemska aloimunosna i autoimunosna bolest koja je najvažnija kasna komplikacija nakon alogenične presadbe krvotvornih matičnih stanica (aloPKMS) i vodeći uzrok ne-relapsnog morbiditeta i smrtnosti nakon aloPKMS. Bolest karakterizira poremećena homeostaza humoralnog imunološkog sustava. Glikoprotein imunoglobulin G (IgG) je glavna efektorska molekula humoralnog imunološkog odgovora. Promjene u glikozilaciji IgG-a povezane su s nizom autoimunosnih bolesti. Glikozilacije IgG-a ispitana je u američkoj (213 cGvHD bolesnika) i hrvatskoj populaciji (30 cGvHD bolesnika i 30 ispitanika kontrolne skupine (transplantirani, bez cGvHD-a)) te je ispitana povezanost glikozilacije IgG-a s demografskim karakteristikama ispitanika i kliničkim manifestacijama cGvHD-a. Analiza američke populacije cGvHD bolesnika pokazala je značajne rezultate u pacijentima s kroničnim cGvHD-om zglobova/fascije i kože, kao i u bolesnika s aktivnim oblikom bolesti te višim stupnjem intenziteta sistemske imunosupresije. Analiza ROC krivuljama pokazala je da glikozilacija IgG-a doprinosi povećanju osjetljivosti i specifičnosti modela izgrađenog na laboratorijskim parametrima i markerima upale. Diskriminativni model izgrađen na hrvatskoj populaciji koristeći glikanske i laboratorijske parametre izdvojio je glikopeptide za koje je opravdano pretpostaviti da značajno doprinose diskriminaciji cGvHD bolesnika od kontrolne skupine. Istraživanjem je pokazano da glikozilacija IgG-a ima ulogu u patologiji cGvHD-a te da bi daljnje istraživanje moglo doprinijeti razumijevanju biologije bolesti i dovesti do nužno potrebnog biomarkera kroničnog GVHD.Chronic graft-versus-host disease (cGvHD) is a systemic alloimmune and autoimmune disorder and the major late complication and leading cause of non-relapse morbidity and mortality after 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 on two populations, American (213 cGvHD patients) and Croatian (30 cGvHD patients and 30 controls (after alloHSCT, without cGvHD)). The American population results showed significant correlation with 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. The Croatian logistic regression model built using glycan and laboratory parameters singled out glycopeptides for which it is justified to assume that they significantly contribute to the cGvHD discrimination. This study has shown that IgG glycosylation plays a significant role in cGvHD pathology, and that further research could contribute to the understanding of the disease biology and lead to the necessary biomarker of chronic GVHD

N-glycosylation of immunoglobulin G in chronic graft-versus-host disease

Kronična bolest presatka protiv primatelja (eng. chronic graft-versus-host disease, cGvHD) je sistemska aloimunosna i autoimunosna bolest koja je najvažnija kasna komplikacija nakon alogenične presadbe krvotvornih matičnih stanica (aloPKMS) i vodeći uzrok ne-relapsnog morbiditeta i smrtnosti nakon aloPKMS. Bolest karakterizira poremećena homeostaza humoralnog imunološkog sustava. Glikoprotein imunoglobulin G (IgG) je glavna efektorska molekula humoralnog imunološkog odgovora. Promjene u glikozilaciji IgG-a povezane su s nizom autoimunosnih bolesti. Glikozilacije IgG-a ispitana je u američkoj (213 cGvHD bolesnika) i hrvatskoj populaciji (30 cGvHD bolesnika i 30 ispitanika kontrolne skupine (transplantirani, bez cGvHD-a)) te je ispitana povezanost glikozilacije IgG-a s demografskim karakteristikama ispitanika i kliničkim manifestacijama cGvHD-a. Analiza američke populacije cGvHD bolesnika pokazala je značajne rezultate u pacijentima s kroničnim cGvHD-om zglobova/fascije i kože, kao i u bolesnika s aktivnim oblikom bolesti te višim stupnjem intenziteta sistemske imunosupresije. Analiza ROC krivuljama pokazala je da glikozilacija IgG-a doprinosi povećanju osjetljivosti i specifičnosti modela izgrađenog na laboratorijskim parametrima i markerima upale. Diskriminativni model izgrađen na hrvatskoj populaciji koristeći glikanske i laboratorijske parametre izdvojio je glikopeptide za koje je opravdano pretpostaviti da značajno doprinose diskriminaciji cGvHD bolesnika od kontrolne skupine. Istraživanjem je pokazano da glikozilacija IgG-a ima ulogu u patologiji cGvHD-a te da bi daljnje istraživanje moglo doprinijeti razumijevanju biologije bolesti i dovesti do nužno potrebnog biomarkera kroničnog GVHD.Chronic graft-versus-host disease (cGvHD) is a systemic alloimmune and autoimmune disorder and the major late complication and leading cause of non-relapse morbidity and mortality after 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 on two populations, American (213 cGvHD patients) and Croatian (30 cGvHD patients and 30 controls (after alloHSCT, without cGvHD)). The American population results showed significant correlation with 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. The Croatian logistic regression model built using glycan and laboratory parameters singled out glycopeptides for which it is justified to assume that they significantly contribute to the cGvHD discrimination. This study has shown that IgG glycosylation plays a significant role in cGvHD pathology, and that further research could contribute to the understanding of the disease biology and lead to the necessary biomarker of chronic GVHD

N-glycosylation of immunoglobulin G in chronic graft-versus-host disease

Kronična bolest presatka protiv primatelja (eng. chronic graft-versus-host disease, cGvHD) je sistemska aloimunosna i autoimunosna bolest koja je najvažnija kasna komplikacija nakon alogenične presadbe krvotvornih matičnih stanica (aloPKMS) i vodeći uzrok ne-relapsnog morbiditeta i smrtnosti nakon aloPKMS. Bolest karakterizira poremećena homeostaza humoralnog imunološkog sustava. Glikoprotein imunoglobulin G (IgG) je glavna efektorska molekula humoralnog imunološkog odgovora. Promjene u glikozilaciji IgG-a povezane su s nizom autoimunosnih bolesti. Glikozilacije IgG-a ispitana je u američkoj (213 cGvHD bolesnika) i hrvatskoj populaciji (30 cGvHD bolesnika i 30 ispitanika kontrolne skupine (transplantirani, bez cGvHD-a)) te je ispitana povezanost glikozilacije IgG-a s demografskim karakteristikama ispitanika i kliničkim manifestacijama cGvHD-a. Analiza američke populacije cGvHD bolesnika pokazala je značajne rezultate u pacijentima s kroničnim cGvHD-om zglobova/fascije i kože, kao i u bolesnika s aktivnim oblikom bolesti te višim stupnjem intenziteta sistemske imunosupresije. Analiza ROC krivuljama pokazala je da glikozilacija IgG-a doprinosi povećanju osjetljivosti i specifičnosti modela izgrađenog na laboratorijskim parametrima i markerima upale. Diskriminativni model izgrađen na hrvatskoj populaciji koristeći glikanske i laboratorijske parametre izdvojio je glikopeptide za koje je opravdano pretpostaviti da značajno doprinose diskriminaciji cGvHD bolesnika od kontrolne skupine. Istraživanjem je pokazano da glikozilacija IgG-a ima ulogu u patologiji cGvHD-a te da bi daljnje istraživanje moglo doprinijeti razumijevanju biologije bolesti i dovesti do nužno potrebnog biomarkera kroničnog GVHD.Chronic graft-versus-host disease (cGvHD) is a systemic alloimmune and autoimmune disorder and the major late complication and leading cause of non-relapse morbidity and mortality after 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 on two populations, American (213 cGvHD patients) and Croatian (30 cGvHD patients and 30 controls (after alloHSCT, without cGvHD)). The American population results showed significant correlation with 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. The Croatian logistic regression model built using glycan and laboratory parameters singled out glycopeptides for which it is justified to assume that they significantly contribute to the cGvHD discrimination. This study has shown that IgG glycosylation plays a significant role in cGvHD pathology, and that further research could contribute to the understanding of the disease biology and lead to the necessary biomarker of chronic GVHD

Joint and fascial chronic graftvs- 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 cGVH

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