Key result
Enterovirus RNA was detected in the pancreas of 53% of single islet autoantibody-positive donors, more frequently than in non-diabetic control donors.
Why the study?
The study was conducted to examine the presence of enterovirus RNA in pancreas and lymphoid tissues of organ donors with and without type 1 diabetes using innovative detection and sequencing technologies.
Cross-Sectional (n=167)
Yes
This study demonstrates that organ donors with type 1 diabetes and those with islet autoantibodies frequently carry a low-grade enterovirus infection in the pancreas and lymphoid tissues.
Answers are grounded in this paper and cite their sources.
Enterovirus RNA more frequent in single-AAb+ donors; leaves open causal role in T1D progression pending prospective studies.
AIMS/HYPOTHESIS: The nPOD-Virus group collaboratively applied innovative technologies to detect and sequence viral RNA in pancreas and other tissues from organ donors with type 1 diabetes. These analyses involved the largest number of pancreas samples collected to date. The aim of the current work was to examine the presence of enterovirus RNA in pancreas and lymphoid tissues of organ donors with and without type 1 diabetes. METHODS: We analysed pancreas, spleen, pancreatic lymph nodes and duodenum samples from the following groups: (1) donors with type 1 diabetes (n=71) with (n=35) or without (n=36) insulin-containing islets; (2) donors with single or double islet autoantibody positivity without diabetes (n=22); and (3) autoantibody-negative donors without diabetes (control donors) (n=74). Five research laboratories participated in this collaborative effort using approaches for unbiased discovery of RNA viruses (two RNA-Seq platforms), targeted detection of Enterovirus A-D species using RT-PCR, and tests for virus growth in cell culture. RESULTS: Direct RNA-Seq did not detect virus signal in pancreas samples, whereas RT-PCR detected enterovirus RNA confirmed by sequencing in low amounts in pancreas samples in three of the five donor groups: donors with type 1 diabetes with insulin-containing islets, 16% (5/32) being positive; donors with single islet autoantibody positivity, 53% (8/15) being positive; and non-diabetic donors, 8% (4/49) being positive. Detection of enterovirus RNA was significantly more frequent in single islet autoantibody-positive donors compared with donors with type 1 diabetes with insulin-deficient islets (p<0.001) and control (non-diabetic) donors (p=0.004). In some donors, pancreatic lymph nodes were also positive. RT-PCR detected enterovirus RNA also in the spleen of a small number of donors and virus enrichment in susceptible cell lines before RT-PCR resulted in much higher rate in spleen positivity, particularly in donors with type 1 diabetes. Interestingly, the enterovirus strains detected did not cause a typical lytic infection, possibly reflecting their persistence-prone nature. CONCLUSIONS/INTERPRETATION: This was the largest coordinated effort to examine the presence of enterovirus RNA in the pancreas of organ donors with type 1 diabetes, using a multitude of assays. These findings are consistent with the notion that donors with type 1 diabetes and donors with islet autoantibodies may carry a low-grade enterovirus infection in the pancreas and lymphoid tissues.
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Laiho et al. (2025) conducted a cross-sectional in Type 1 diabetes and islet autoantibody positivity (n=167). Islet autoantibody positivity vs. Autoantibody-negative donors without diabetes was evaluated on Detection of enterovirus RNA in pancreas samples by RT-PCR (p=0.004). Enterovirus RNA was detected in the pancreas of 53% of single islet autoantibody-positive donors, more frequently than in non-diabetic control donors.
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