Human complement component C3 N-glycome changes in type 1 diabetes complications
Changes in N-glycosylation have been described in numerous diseases and are being considered as biomarkers of ongoing pathological condition. Previous studies demonstrated the interrelation of N-glycosylation and type 1 diabetes (T1D), particularly linking serum N-glycan changes with complications a...
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| Vydané v: | Frontiers in endocrinology (Lausanne) Ročník 14; s. 1101154 |
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| Hlavní autori: | , , , , , , , , , , , |
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| Jazyk: | English |
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Switzerland
Frontiers Media S.A
24.05.2023
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| ISSN: | 1664-2392, 1664-2392 |
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| Abstract | Changes in N-glycosylation have been described in numerous diseases and are being considered as biomarkers of ongoing pathological condition. Previous studies demonstrated the interrelation of N-glycosylation and type 1 diabetes (T1D), particularly linking serum N-glycan changes with complications accompanying the disease. Moreover, the role of complement component C3 in diabetic nephropathy and retinopathy has been implicated, and C3 N-glycome was found to be altered in young T1D patients. Therefore, we investigated associations between C3 N-glycan profiles and albuminuria and retinopathy accompanying T1D, as well as glycosylation connection with other known T1D complication risk factors.
Complement component C3 N-glycosylation profiles have been analyzed from 189 serum samples of T1D patients (median age 46) recruited at a Croatian hospital centre. Using our recently developed high-throughput method, relative abundances of all six of the C3 glycopeptides have been determined. Assessment of C3 N-glycome interconnection with T1D complications, hypertension, smoking status, estimated glomerular filtration rate (eGFR), glycaemic control and duration of the disease was done using linear modelling.
Significant changes of C3 N-glycome in severe albuminuria accompanying type 1 diabetes were observed, as well as in T1D subjects with hypertension. All except one of the C3 glycopeptides proved to be associated with measured HbA1c levels. One of the glycoforms was shown to be changed in non-proliferative T1D retinopathy. Smoking and eGFR showed no effect on C3 N-glycome. Furthermore, C3 N-glycosylation profile was shown to be independent of disease duration.
This study empowered the role of C3 N-glycosylation in T1D, showing value in distinguishing subjects with different diabetic complications. Being independent of the disease duration, these changes may be associated with the disease onset, making C3 N-glycome a potential novel marker of the disease progression and severity. |
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| AbstractList | AimChanges in N-glycosylation have been described in numerous diseases and are being considered as biomarkers of ongoing pathological condition. Previous studies demonstrated the interrelation of N-glycosylation and type 1 diabetes (T1D), particularly linking serum N-glycan changes with complications accompanying the disease. Moreover, the role of complement component C3 in diabetic nephropathy and retinopathy has been implicated, and C3 N-glycome was found to be altered in young T1D patients. Therefore, we investigated associations between C3 N-glycan profiles and albuminuria and retinopathy accompanying T1D, as well as glycosylation connection with other known T1D complication risk factors.Research design and methodsComplement component C3 N-glycosylation profiles have been analyzed from 189 serum samples of T1D patients (median age 46) recruited at a Croatian hospital centre. Using our recently developed high-throughput method, relative abundances of all six of the C3 glycopeptides have been determined. Assessment of C3 N-glycome interconnection with T1D complications, hypertension, smoking status, estimated glomerular filtration rate (eGFR), glycaemic control and duration of the disease was done using linear modelling.ResultsSignificant changes of C3 N-glycome in severe albuminuria accompanying type 1 diabetes were observed, as well as in T1D subjects with hypertension. All except one of the C3 glycopeptides proved to be associated with measured HbA1c levels. One of the glycoforms was shown to be changed in non-proliferative T1D retinopathy. Smoking and eGFR showed no effect on C3 N-glycome. Furthermore, C3 N-glycosylation profile was shown to be independent of disease duration.ConclusionThis study empowered the role of C3 N-glycosylation in T1D, showing value in distinguishing subjects with different diabetic complications. Being independent of the disease duration, these changes may be associated with the disease onset, making C3 N-glycome a potential novel marker of the disease progression and severity. Changes in N-glycosylation have been described in numerous diseases and are being considered as biomarkers of ongoing pathological condition. Previous studies demonstrated the interrelation of N-glycosylation and type 1 diabetes (T1D), particularly linking serum N-glycan changes with complications accompanying the disease. Moreover, the role of complement component C3 in diabetic nephropathy and retinopathy has been implicated, and C3 N-glycome was found to be altered in young T1D patients. Therefore, we investigated associations between C3 N-glycan profiles and albuminuria and retinopathy accompanying T1D, as well as glycosylation connection with other known T1D complication risk factors.AimChanges in N-glycosylation have been described in numerous diseases and are being considered as biomarkers of ongoing pathological condition. Previous studies demonstrated the interrelation of N-glycosylation and type 1 diabetes (T1D), particularly linking serum N-glycan changes with complications accompanying the disease. Moreover, the role of complement component C3 in diabetic nephropathy and retinopathy has been implicated, and C3 N-glycome was found to be altered in young T1D patients. Therefore, we investigated associations between C3 N-glycan profiles and albuminuria and retinopathy accompanying T1D, as well as glycosylation connection with other known T1D complication risk factors.Complement component C3 N-glycosylation profiles have been analyzed from 189 serum samples of T1D patients (median age 46) recruited at a Croatian hospital centre. Using our recently developed high-throughput method, relative abundances of all six of the C3 glycopeptides have been determined. Assessment of C3 N-glycome interconnection with T1D complications, hypertension, smoking status, estimated glomerular filtration rate (eGFR), glycaemic control and duration of the disease was done using linear modelling.Research design and methodsComplement component C3 N-glycosylation profiles have been analyzed from 189 serum samples of T1D patients (median age 46) recruited at a Croatian hospital centre. Using our recently developed high-throughput method, relative abundances of all six of the C3 glycopeptides have been determined. Assessment of C3 N-glycome interconnection with T1D complications, hypertension, smoking status, estimated glomerular filtration rate (eGFR), glycaemic control and duration of the disease was done using linear modelling.Significant changes of C3 N-glycome in severe albuminuria accompanying type 1 diabetes were observed, as well as in T1D subjects with hypertension. All except one of the C3 glycopeptides proved to be associated with measured HbA1c levels. One of the glycoforms was shown to be changed in non-proliferative T1D retinopathy. Smoking and eGFR showed no effect on C3 N-glycome. Furthermore, C3 N-glycosylation profile was shown to be independent of disease duration.ResultsSignificant changes of C3 N-glycome in severe albuminuria accompanying type 1 diabetes were observed, as well as in T1D subjects with hypertension. All except one of the C3 glycopeptides proved to be associated with measured HbA1c levels. One of the glycoforms was shown to be changed in non-proliferative T1D retinopathy. Smoking and eGFR showed no effect on C3 N-glycome. Furthermore, C3 N-glycosylation profile was shown to be independent of disease duration.This study empowered the role of C3 N-glycosylation in T1D, showing value in distinguishing subjects with different diabetic complications. Being independent of the disease duration, these changes may be associated with the disease onset, making C3 N-glycome a potential novel marker of the disease progression and severity.ConclusionThis study empowered the role of C3 N-glycosylation in T1D, showing value in distinguishing subjects with different diabetic complications. Being independent of the disease duration, these changes may be associated with the disease onset, making C3 N-glycome a potential novel marker of the disease progression and severity. Changes in N-glycosylation have been described in numerous diseases and are being considered as biomarkers of ongoing pathological condition. Previous studies demonstrated the interrelation of N-glycosylation and type 1 diabetes (T1D), particularly linking serum N-glycan changes with complications accompanying the disease. Moreover, the role of complement component C3 in diabetic nephropathy and retinopathy has been implicated, and C3 N-glycome was found to be altered in young T1D patients. Therefore, we investigated associations between C3 N-glycan profiles and albuminuria and retinopathy accompanying T1D, as well as glycosylation connection with other known T1D complication risk factors. Complement component C3 N-glycosylation profiles have been analyzed from 189 serum samples of T1D patients (median age 46) recruited at a Croatian hospital centre. Using our recently developed high-throughput method, relative abundances of all six of the C3 glycopeptides have been determined. Assessment of C3 N-glycome interconnection with T1D complications, hypertension, smoking status, estimated glomerular filtration rate (eGFR), glycaemic control and duration of the disease was done using linear modelling. Significant changes of C3 N-glycome in severe albuminuria accompanying type 1 diabetes were observed, as well as in T1D subjects with hypertension. All except one of the C3 glycopeptides proved to be associated with measured HbA1c levels. One of the glycoforms was shown to be changed in non-proliferative T1D retinopathy. Smoking and eGFR showed no effect on C3 N-glycome. Furthermore, C3 N-glycosylation profile was shown to be independent of disease duration. This study empowered the role of C3 N-glycosylation in T1D, showing value in distinguishing subjects with different diabetic complications. Being independent of the disease duration, these changes may be associated with the disease onset, making C3 N-glycome a potential novel marker of the disease progression and severity. |
| Author | Novokmet, Mislav Lovrenčić, Marijana Vučić Rebrina, Sandra Vučković Smirčić-Duvnjak, Lea Tomić, Martina Štambuk, Jerko Šoić, Dinko Keser, Toma Bulum, Tomislav Tijardović, Marko Lauc, Gordan Gornik, Olga |
| AuthorAffiliation | 2 Genos Glycoscience Research Laboratory , Zagreb , Croatia 3 Department of Endocrinology, University Clinic Vuk Vrhovac , Zagreb , Croatia 4 School of Medicine, University of Zagreb , Zagreb , Croatia 1 Faculty of Pharmacy and Biochemistry, University of Zagreb , Zagreb , Croatia 5 Department of Medical Biochemistry and Laboratory Medicine, University Hospital Merkur , Zagreb , Croatia |
| AuthorAffiliation_xml | – name: 4 School of Medicine, University of Zagreb , Zagreb , Croatia – name: 5 Department of Medical Biochemistry and Laboratory Medicine, University Hospital Merkur , Zagreb , Croatia – name: 3 Department of Endocrinology, University Clinic Vuk Vrhovac , Zagreb , Croatia – name: 2 Genos Glycoscience Research Laboratory , Zagreb , Croatia – name: 1 Faculty of Pharmacy and Biochemistry, University of Zagreb , Zagreb , Croatia |
| Author_xml | – sequence: 1 givenname: Dinko surname: Šoić fullname: Šoić, Dinko – sequence: 2 givenname: Jerko surname: Štambuk fullname: Štambuk, Jerko – sequence: 3 givenname: Marko surname: Tijardović fullname: Tijardović, Marko – sequence: 4 givenname: Toma surname: Keser fullname: Keser, Toma – sequence: 5 givenname: Gordan surname: Lauc fullname: Lauc, Gordan – sequence: 6 givenname: Tomislav surname: Bulum fullname: Bulum, Tomislav – sequence: 7 givenname: Marijana Vučić surname: Lovrenčić fullname: Lovrenčić, Marijana Vučić – sequence: 8 givenname: Sandra Vučković surname: Rebrina fullname: Rebrina, Sandra Vučković – sequence: 9 givenname: Martina surname: Tomić fullname: Tomić, Martina – sequence: 10 givenname: Mislav surname: Novokmet fullname: Novokmet, Mislav – sequence: 11 givenname: Lea surname: Smirčić-Duvnjak fullname: Smirčić-Duvnjak, Lea – sequence: 12 givenname: Olga surname: Gornik fullname: Gornik, Olga |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/37293493$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1159/000371426 10.1097/HJH.0000000000002963 10.1210/jc.2003-030742 10.2337/diabetes.54.5.1523 10.1007/s00125-010-1742-8 10.2337/dc17-1042 10.1021/pr2004067 10.1093/glycob/cwaa106 10.1111/j.2517-6161.1995.tb02031.x 10.1002/1873-3468.13495 10.1007/s00125-012-2462-z 10.2337/dc19-1507 10.1080/14656566.2020.1729124 10.1016/j.smim.2013.04.003 10.1093/bioinformatics/bts034 10.1136/bmjdrc-2021-002345 10.1007/s00125-017-4426-9 10.1016/S0140-6736(06)68341-4 10.1093/glycob/cwq051 10.1016/j.molimm.2019.07.031 10.1007/s00125-011-2301-7 10.1186/s13148-019-0730-1 10.1038/nbt.2377 10.1186/s12967-018-1695-0 10.2337/diabetes.54.10.3002 10.1021/acs.jproteome.6b00171 10.1016/j.cmet.2018.09.009 10.1016/j.mcpro.2022.100407 10.1007/s00125-004-1594-1 10.1016/j.bbagen.2015.10.016 10.4049/jimmunol.162.7.4336 10.1097/MD.0000000000003379 10.1016/S0140-6736(18)31320-5 10.1161/CIRCULATIONAHA.108.775155 10.1007/s11892-017-0842-y 10.1186/1471-2105-12-77 10.2337/dc14-1873 10.1016/S0140-6736(13)60591-7 10.1001/archinternmed.2008.2 10.1016/0014-5793(86)80649-4 |
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| Copyright | Copyright © 2023 Šoić, Štambuk, Tijardović, Keser, Lauc, Bulum, Lovrenčić, Rebrina, Tomić, Novokmet, Smirčić-Duvnjak and Gornik. Copyright © 2023 Šoić, Štambuk, Tijardović, Keser, Lauc, Bulum, Lovrenčić, Rebrina, Tomić, Novokmet, Smirčić-Duvnjak and Gornik 2023 Šoić, Štambuk, Tijardović, Keser, Lauc, Bulum, Lovrenčić, Rebrina, Tomić, Novokmet, Smirčić-Duvnjak and Gornik |
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| Keywords | LC-MS glycopeptides type 1 diabetes complications complement component (C3) N-glycosylation |
| Language | English |
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| SubjectTerms | Albuminuria - etiology complement component (C3) Diabetes Mellitus, Type 1 - complications Diabetic Retinopathy - complications Endocrinology Glycopeptides Humans LC-MS Middle Aged N-glycosylation Polysaccharides type 1 diabetes complications |
| Title | Human complement component C3 N-glycome changes in type 1 diabetes complications |
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