Insulitis and Exocrinitis in Autoantibody-positive Nondiabetic Individuals: Role of HLA Genotypes
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Bibliographic record
Abstract
CONTEXT: Type 1 diabetes (T1D) is characterized by the presence of autoantibodies on a genetic background largely determined by HLA class II haplotypes. Stage 1 T1D is characterized by the presence of multiple autoantibodies and normoglycemia. OBJECTIVE: To investigate the prevalence of high-risk HLA-DQB1 haplotypes and the extent of islet autoimmunity in pancreatic tissues from nondiabetic organ donors with autoantibodies. DESIGN: We analyzed 117 virtual pancreatic slides from 30 antibody-positive nondiabetic donors from the Network for Pancreatic Organ Donors with Diabetes (nPOD). PATIENTS: Thirty nondiabetic individuals positive for ≥1 autoantibody. HLA haplotypes were classified as at risk (DQ2, namely DQB1*02:01 and/or DQ8, namely DQB1*03:02), protective (DQ6, namely DQB1*06:02) or neutral (other HLA-DQ alleles). MAIN OUTCOME MEASURE: CD3+ lymphocyte infiltration of both endocrine and exocrine pancreas, according to HLA. RESULTS: Among these 30 individuals with a median age of 25 years (interquartile range 21-39); median body mass index 24 kg/m2 (21-30), 23 were single autoantibody-positive and 7 were positive for 2 autoantibodies. β-cell mass was normal in all. HLA-DQ allele distribution was similar to that of autoantibody-negative nondiabetic nPOD donors and differed from that of nPOD donors with stage 3 T1D. Insulitis was identified only in 1 case. CD3+ lymphocyte densities did no correlate with HLA status or autoantibody number or titers, neither in islets nor in the exocrine pancreas. CONCLUSION: Contrary to stage 3 T1D, autoantibody-positive donors had normal β-cell mass and no significant insulitis, suggesting heterogeneity in the progression of autoimmunity, even in the presence of genetic risk, rather than a uniform slow-progressing process.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it