Single Autoantibody Positive Organ Donors in nPOD May Not Differ From Controls

Background: Staging of preclinical type 1 diabetes (T1D) begins with the development of multiple autoantibodies (AAb). Single AAb have shown lower risk (14.5% risk of T1D within 10 years) and may result in reversion to no AAb, persistence as single AAb, or progression to 2 or more AAb. It remains unclear if the single AAb state offers an appreciable risk of disease or is categorically different from those without AAbs.

Methods: This study assessed clinical, biochemical, immunological, and histopathological differences between organ donors with single AAb, multiple AAb, T1D, and control donors without diabetes from the Network for Pancreatic Organ donors with Diabetes (nPOD).

Results: There were no differences between donor types with respect to gender or race (n=303). More multiple AAb donors (6/7, 86%) had the HLA DR4 genotype than single AAb (7/23, 30%) (p=0.02) and control donors (43/142, 30%) (p=0.008). HLA DQ8 was significantly higher in those with T1D compared to single AAb (p=0.02) and control donors (p<0.001). Histopathology revealed insulitis was present in a similar percent, 29% (2/7) and 26% (33/127), of multiple AAb and T1D donors, respectively; however, only 1/23 (4%) single AAb donors had insulitis present, significantly different from T1D (p=0.03). Comparisons of AAb type/titer were limited by small sample size; GADA titers were similar in single AAb and T1D donors. Relative pancreas weight, C-peptide, and HbA1c were only significantly different compared to those with T1D and could not differentiate AAb donors from controls. HLA DR4 and DQ8 were more common in multiple AAb and T1D donors but not single AAb donors. Albeit a relatively small ?n?, in summary, single AAb donors were overall more similar to controls than multiple AAb or T1D donors