Anti-CD20 Therapy Alters the Protein Signature in Experimental Murine AIH, but Not Exclusively towards Regeneration.
anti-CD20 therapy
autoimmune hepatitis
hepatic inflammation
immune tolerance
regeneration
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
11 06 2021
11 06 2021
Historique:
received:
01
05
2021
revised:
06
06
2021
accepted:
08
06
2021
entrez:
2
7
2021
pubmed:
3
7
2021
medline:
9
11
2021
Statut:
epublish
Résumé
Autoimmune hepatitis (AIH) is a chronic autoimmune inflammatory disease that usually requires lifelong immunosuppression. Frequent recurrences after the discontinuation of therapy indicate that intrahepatic immune regulation is not restored by current treatments. Studies of other autoimmune diseases suggest that temporary depletion of B cells can improve disease progression in the long term. We tested a single administration of anti-CD20 antibodies to reduce B cells and the amount of IgG to induce intrahepatic immune tolerance. We used our experimental murine AIH (emAIH) model and treated the mice with anti-CD20 during the late stage of the disease. After treatment, the mice showed the expected reductions in B cells and serum IgGs, but no improvements in pathology. However, all treated animals showed a highly altered serum protein expression pattern, which was a balance between inflammation and regeneration. In conclusion, anti-CD20 therapy did not produce clinically measurable results because it triggered inflammation, as well as regeneration, at the proteomic level. This finding suggests that anti-CD20 is ineffective as a sole treatment for AIH or emAIH.
Sections du résumé
BACKGROUND
Autoimmune hepatitis (AIH) is a chronic autoimmune inflammatory disease that usually requires lifelong immunosuppression. Frequent recurrences after the discontinuation of therapy indicate that intrahepatic immune regulation is not restored by current treatments. Studies of other autoimmune diseases suggest that temporary depletion of B cells can improve disease progression in the long term.
METHODS
We tested a single administration of anti-CD20 antibodies to reduce B cells and the amount of IgG to induce intrahepatic immune tolerance. We used our experimental murine AIH (emAIH) model and treated the mice with anti-CD20 during the late stage of the disease.
RESULTS
After treatment, the mice showed the expected reductions in B cells and serum IgGs, but no improvements in pathology. However, all treated animals showed a highly altered serum protein expression pattern, which was a balance between inflammation and regeneration.
CONCLUSIONS
In conclusion, anti-CD20 therapy did not produce clinically measurable results because it triggered inflammation, as well as regeneration, at the proteomic level. This finding suggests that anti-CD20 is ineffective as a sole treatment for AIH or emAIH.
Identifiants
pubmed: 34208308
pii: cells10061471
doi: 10.3390/cells10061471
pmc: PMC8231180
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antigens, CD20
0
Autoantibodies
0
Proteome
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : BU2722/2-1
Organisme : Deutsche Forschungsgemeinschaft
ID : BU2722/2-3
Organisme : Deutsche Forschungsgemeinschaft
ID : HA 6880/2-1
Organisme : Deutsche Forschungsgemeinschaft
ID : HA 6880/2-3
Organisme : Deutsche Forschungsgemeinschaft
ID : KFO250; Project 7
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