Joint analysis of the nPOD-Virus Group data: the association of enterovirus with type 1 diabetes is supported by multiple markers of infection in pancreas tissue
Authors' conclusion
The nPOD-Virus Group conducted, to date, the largest and most comprehensive analysis of multiple indices of pancreatic enterovirus infections in type 1 diabetes; these were more prevalent in T1D-ICI and AAb++ donors than in other groups. Their preferential detection of these indices in donors with residual beta cells and autoimmunity implicates enterovirus infections across disease progression stages and supports a contribution to beta cell loss, directly or indirectly, even after diagnosis. The relatively small number of infected cells and the low amount of viral RNA support the existence of non-acute, low level, possibly persistent enterovirus infections in the pancreas.
Study context
- Population
- nPOD organ donors (pancreases recovered 2007–2019) with T1D, with disease-associated AAbs or without diabetes645 assays
- Participants
- 197 donors
- Exposure
- Enterovirus markers in pancreas across T1D, AAb-positive and non-diabetic donors
- T1D-ICIn = 41
- T1D-IDIn = 42
- NDn = 83reference
- AAb+n = 22
- AAb++n = 9
- Outcome
- Proportion of positive enterovirus assay outcomes
Methodological detailsjoint analysis of multiple enterovirus markers, multi-laboratory
- Joint analysis of multiple enterovirus markers
- Multi-laboratory
Main finding
As reported in the abstract
P < 0.001
Observational data: associations, not effects.
Further findings
| Outcome | Values | P value |
|---|---|---|
| Donors positive in two independent assays, T1D-ICI vs NDT1D-ICI vs ND · increased with T1D-ICI | VP1/HLA-I, p<0.0001 | |
| Donors positive in two independent assays, T1D-ICI vs NDT1D-ICI vs ND | VP1/EV-PCR, p=0.076 | |
| Donors positive in two independent assays, T1D-ICI vs NDT1D-ICI vs ND · increased with T1D-ICI | EV-PCR/HLA-I, p=0.016 | |
| Donors positive in two independent assays, T1D-ICI vs NDT1D-ICI vs ND · increased with T1D-ICI | proteomics/HLA-I, p<0.0001 | |
| Donors positive in two independent assays, T1D-ICI vs NDT1D-ICI vs ND | VP1/proteomics, p=0.06 | |
| Positive in ≥2 of 3 assays (VP1, EV-PCR, HLA-I)T1D-ICI vs ND | T1D-ICI 83.3% · ND 0% · AAb+ 26.7% · AAb++ 28.6% · T1D-IDI 0% | P < 0.001 |
| Positive in ≥2 of 3 assays (VP1, EV-PCR, HLA-I)T1D-ICI vs AAb+ | P = 0.006 | |
| Positive in ≥2 of 3 assays (VP1, EV-PCR, HLA-I)T1D-ICI vs AAb++ | P = 0.023 | |
| Positive in ≥2 of 3 assays (VP1, EV-PCR, HLA-I)T1D-ICI vs T1D-IDI | P < 0.001 |
- Positive in ≥2 of 3 assays (VP1, EV-PCR, HLA-I): 110 donors examined for three markers
Original publication
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