Enterovirus VP1 protein and HLA class I hyperexpression in pancreatic islet cells of organ donors with type 1 diabetes
Authors' conclusion
We report the most extensive analysis to date of VP1 and HLA-I in pancreases from donors with preclinical and diagnosed type 1 diabetes. We find an association of VP1 with residual beta cells after diagnosis and demonstrate VP1 positivity during the autoantibody-positive preclinical stage. For the first time, we show that VP1 positivity and HLA-I hyperexpression in islet cells are both present during the preclinical stage. While the study of tissues does not allow us to demonstrate causality, our data support the hypothesis that enterovirus infections may occur throughout the natural history of type 1 diabetes and may be one of multiple mechanisms driving islet cell HLA-I hyperexpression.
Study context
- Population
- Organ donors (nPOD), including donors with T1D and donors expressing autoantibody risk markers; pancreas, spleen, duodenum and pancreatic lymph nodes
- Participants
- 188 organ donors
- Exposure
- VP1 positivity and HLA-I hyperexpression in islet cells across donor groups (ND, AAb+, AAb++, T1D-ICIs, T1D-IDIs)
- NDn = 76reference
- AAb+n = 20
- AAb++n = 9
- T1D-ICIsn = 41
- T1D-IDIsn = 42
- Outcome
- Islet cell VP1 positivity (IHC) and its link to HLA-I hyperexpression
Methodological detailsorgan donor tissues (nPOD), two independent laboratories, VP1 by immunohistochemistry (IHC); HLA-I by IHC and immunofluorescence, in two independent laboratories
- Organ donor tissues (nPOD)
- Two independent laboratories
- VP1 by IHC; HLA-I by IHC and immunofluorescence, in two independent laboratories
Main finding
As reported in the abstract
P < 0.001
Observational data: associations, not effects.
Further findings
HLA-I hyperexpression, all donor groups combined
P < 0.001
Both VP1 immunopositivity and HLA-I hyperexpression, among donors assessed for both
- Donors with both VP1 positivity and HLA-I hyperexpression (p<0.001 vs ND)
- 73.7%
VP1+ cell frequency by HLA-I status
- VP1+ cells detected at higher frequency in donors with HLA-I hyperexpression (p<0.001 vs normal HLA-I)
HLA-I hyperexpression among VP1+ donors, AAb++ and T1D-ICIs
- Proportion with HLA-I hyperexpression in AAb++ and T1D-ICI groups (p<0.001 vs ND); not restricted to recent-onset diabetes
- 94.9%
Original publication
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