High levels of blood circulating immune checkpoint molecules in children with new-onset type 1 diabetes are associated with the risk of developing an additional autoimmune disease
Aims/hypothesis We assessed the levels of blood circulating immune checkpoint molecules (ICMs) at diagnosis of type 1 diabetes, and determined their association with the risk of developing an additional autoimmune disorder over time. Methods Children with new-onset type 1 diabetes (n = 143), without biological and/or clinical signs of additional autoimmune disorders, and healthy children (n = 75) were enrolled, and blood circulating levels of 14 ICMs were measured. The children with type 1 diabetes were divided into two groups on the basis of the development of an additional autoimmune disease in the 5 years after diabetes onset. Differences in soluble ICM levels between the groups were assessed, and a Cox regression analysis was used to evaluate their association with the risk of development of an additional autoimmune disease over time. To validate the data, circulating ICMs were measured in an independent cohort of 60 children with new-onset type 1 diabetes stratified into two groups. Results We found that the levels of circulating ICMs were significantly higher in children with new-onset diabetes compared with healthy children. Further, we observed that children with type 1 diabetes who developed a second autoimmune disease over time (T1D-$ AAD^{+} $ children) had higher levels of soluble ICMs than children with type 1 diabetes who did not (T1D-$ AAD^{−} $ children). Cox regression models revealed that high circulating levels of CD137/4-1BB and PD-1 molecules at diabetes diagnosis were associated with the risk of developing an additional autoimmune disease in both type 1 diabetes cohorts. Conclusions/interpretation Our findings suggest that soluble CD137/4-1BB and PD-1 molecules may be used as prognostic biomarkers in children with type 1 diabetes, and may pave the way for novel immunological screening at diabetes onset, allowing early identification of children at higher risk of developing other autoimmune conditions over time. Graphical abstract.
| Medienart: |
Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:65 |
|---|---|
| Enthalten in: |
Diabetologia - 65(2022), 8 vom: 25. Mai, Seite 1390-1397 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Bruzzaniti, Sara [VerfasserIn] |
|---|
| Links: |
Volltext [lizenzpflichtig] |
|---|
| Themen: |
Autoimmune diseases |
|---|
| RVK: |
|---|
| Anmerkungen: |
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022 |
|---|
| doi: |
10.1007/s00125-022-05724-3 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
OLC2079144235 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | OLC2079144235 | ||
| 003 | DE-627 | ||
| 005 | 20230513105040.0 | ||
| 007 | tu | ||
| 008 | 221220s2022 xx ||||| 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s00125-022-05724-3 |2 doi | |
| 035 | |a (DE-627)OLC2079144235 | ||
| 035 | |a (DE-He213)s00125-022-05724-3-p | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | 4 | |a 610 |q VZ |
| 082 | 0 | 4 | |a 610 |q VZ |
| 084 | |a XA 40615 |q VZ |2 rvk | ||
| 100 | 1 | |a Bruzzaniti, Sara |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a High levels of blood circulating immune checkpoint molecules in children with new-onset type 1 diabetes are associated with the risk of developing an additional autoimmune disease |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022 | ||
| 520 | |a Aims/hypothesis We assessed the levels of blood circulating immune checkpoint molecules (ICMs) at diagnosis of type 1 diabetes, and determined their association with the risk of developing an additional autoimmune disorder over time. Methods Children with new-onset type 1 diabetes (n = 143), without biological and/or clinical signs of additional autoimmune disorders, and healthy children (n = 75) were enrolled, and blood circulating levels of 14 ICMs were measured. The children with type 1 diabetes were divided into two groups on the basis of the development of an additional autoimmune disease in the 5 years after diabetes onset. Differences in soluble ICM levels between the groups were assessed, and a Cox regression analysis was used to evaluate their association with the risk of development of an additional autoimmune disease over time. To validate the data, circulating ICMs were measured in an independent cohort of 60 children with new-onset type 1 diabetes stratified into two groups. Results We found that the levels of circulating ICMs were significantly higher in children with new-onset diabetes compared with healthy children. Further, we observed that children with type 1 diabetes who developed a second autoimmune disease over time (T1D-$ AAD^{+} $ children) had higher levels of soluble ICMs than children with type 1 diabetes who did not (T1D-$ AAD^{−} $ children). Cox regression models revealed that high circulating levels of CD137/4-1BB and PD-1 molecules at diabetes diagnosis were associated with the risk of developing an additional autoimmune disease in both type 1 diabetes cohorts. Conclusions/interpretation Our findings suggest that soluble CD137/4-1BB and PD-1 molecules may be used as prognostic biomarkers in children with type 1 diabetes, and may pave the way for novel immunological screening at diabetes onset, allowing early identification of children at higher risk of developing other autoimmune conditions over time. Graphical abstract | ||
| 650 | 4 | |a Autoimmune diseases | |
| 650 | 4 | |a Autoimmune thyroiditis | |
| 650 | 4 | |a Biomarkers | |
| 650 | 4 | |a Coeliac disease | |
| 650 | 4 | |a Soluble immune-checkpoint molecules | |
| 650 | 4 | |a Type 1 diabetes | |
| 700 | 1 | |a Piemonte, Erica |4 aut | |
| 700 | 1 | |a Mozzillo, Enza |4 aut | |
| 700 | 1 | |a Bruzzese, Dario |4 aut | |
| 700 | 1 | |a Lepore, Maria Teresa |4 aut | |
| 700 | 1 | |a Carbone, Fortunata |4 aut | |
| 700 | 1 | |a de Candia, Paola |4 aut | |
| 700 | 1 | |a Strollo, Rocky |4 aut | |
| 700 | 1 | |a Porcellini, Antonio |4 aut | |
| 700 | 1 | |a Marigliano, Marco |4 aut | |
| 700 | 1 | |a Maffeis, Claudio |4 aut | |
| 700 | 1 | |a Bifulco, Maurizio |4 aut | |
| 700 | 1 | |a Ludvigsson, Johnny |4 aut | |
| 700 | 1 | |a Franzese, Adriana |4 aut | |
| 700 | 1 | |a Matarese, Giuseppe |4 aut | |
| 700 | 1 | |a Galgani, Mario |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Diabetologia |d Springer Berlin Heidelberg, 1965 |g 65(2022), 8 vom: 25. Mai, Seite 1390-1397 |w (DE-627)129069140 |w (DE-600)1694-9 |w (DE-576)014400847 |x 0012-186X |7 nnns |
| 773 | 1 | 8 | |g volume:65 |g year:2022 |g number:8 |g day:25 |g month:05 |g pages:1390-1397 |
| 856 | 4 | 1 | |u https://doi.org/10.1007/s00125-022-05724-3 |z lizenzpflichtig |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a SYSFLAG_A | ||
| 912 | |a GBV_OLC | ||
| 912 | |a SSG-OLC-PHA | ||
| 912 | |a SSG-OLC-DE-84 | ||
| 912 | |a GBV_ILN_267 | ||
| 912 | |a GBV_ILN_2018 | ||
| 912 | |a GBV_ILN_4277 | ||
| 936 | r | v | |a XA 40615 |
| 951 | |a AR | ||
| 952 | |d 65 |j 2022 |e 8 |b 25 |c 05 |h 1390-1397 | ||