1. |
|
|
2. |
|
|
3. |
|
|
4. |
|
|
5. |
|
|
6. |
|
|
7. |
|
|
8. |
|
|
9. |
|
|
10. |
|
|
11. |
- Harre, U, et al.
(författare)
-
Glycosylation of immunoglobulin G determines osteoclast differentiation and bone loss
- 2015
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6, s. 6651-
-
Tidskriftsartikel (refereegranskat)abstract
- Immunglobulin G (IgG) sialylation represents a key checkpoint that determines the engagement of pro- or anti-inflammatory Fcγ receptors (FcγR) and the direction of the immune response. Whether IgG sialylation influences osteoclast differentiation and subsequently bone architecture has not been determined yet, but may represent an important link between immune activation and bone loss. Here we demonstrate that desialylated, but not sialylated, immune complexes enhance osteoclastogenesis in vitro and in vivo. Furthermore, we find that the Fc sialylation state of random IgG and specific IgG autoantibodies determines bone architecture in patients with rheumatoid arthritis. In accordance with these findings, mice treated with the sialic acid precursor N-acetylmannosamine (ManNAc), which results in increased IgG sialylation, are less susceptible to inflammatory bone loss. Taken together, our findings provide a novel mechanism by which immune responses influence the human skeleton and an innovative treatment approach to inhibit immune-mediated bone loss.
|
|
12. |
|
|
13. |
|
|
14. |
- Kissel, T, et al.
(författare)
-
Surface Ig variable domain glycosylation affects autoantigen binding and acts as threshold for human autoreactive B cell activation
- 2022
-
Ingår i: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:6, s. eabm1759-
-
Tidskriftsartikel (refereegranskat)abstract
- The hallmark autoantibodies in rheumatoid arthritis are characterized by variable domain glycans (VDGs). Their abundant occurrence results from the selective introduction of N-linked glycosylation sites during somatic hypermutation, and their presence is predictive for disease development. However, the functional consequences of VDGs on autoreactive B cells remain elusive. Combining crystallography, glycobiology, and functional B cell assays allowed us to dissect key characteristics of VDGs on human B cell biology. Crystal structures showed that VDGs are positioned in the vicinity of the antigen-binding pocket, and dynamic modeling combined with binding assays elucidated their impact on binding. We found that VDG-expressing B cell receptors stay longer on the B cell surface and that VDGs enhance B cell activation. These results provide a rationale on how the acquisition of VDGs might contribute to the breach of tolerance of autoreactive B cells in a major human autoimmune disease.
|
|
15. |
|
|
16. |
|
|
17. |
|
|
18. |
|
|
19. |
|
|
20. |
|
|
21. |
|
|
22. |
|
|
23. |
|
|
24. |
|
|
25. |
|
|
26. |
|
|
27. |
|
|
28. |
|
|