MHC Class I Chain‐Related Gene‐A Is Associated with IA2 and IAA but Not GAD in Swedish Type 1 Diabetes Mellitus
Bibliographic record
Abstract
In type 1 diabetes mellitus (T1DM), the frequency of antibodies against insulin (IAA), glutamic acid decarboxylase-65 (GAD65), ICA512/IA2 (IA2), and islet cell antigens (ICA) vary with human leukocyte antigen (HLA) composition of the patient. IAA, IA2 autoantibodies, and ICA are increased in DQ8 positives; GAD65 antibodies are increased in DQ2 positives. MHC class I chain-related gene-A (MICA) is another genetic marker that has been proposed to be associated with T1DM. In this article, we looked at microsatellite polymorphism of MICA and its association with autoantibodies (IAA, IA2, and GAD65) in Swedish T1DM patients and if the association explains its importance in early events in autoimmune response. We studied 635 T1DM patients between 0-35 years. Frequency of MICA5/5 was positively associated with the formation of IAA and IA2 antibodies considered individually or in combination (odds ratio [OR], 95% CI, Pc: [IAA+ versus IAA-]: 4.94, 2.09-11.62, <0.0005; [IA2+ versus IA2-]: 2.65, 1.52-4.59, 0.0015; [IAA and/or IA2+ versus rest]: 9.83, 2.37-40.78, <0.0015; [IAA and IA2+ versus rest]: 3.51, 2.01-6.15, <0.0015). Also, -5.1/5.1 was increased in IAA+ patients compared to IAA- patients (2.82, 1.64-4.83, <0.0005). All patients positive for -5/5 developed at least one of the three antibodies. Frequency of MICA5.1 was decreased in IAA+ (0.54, 0.36-0.81, 0.017), in IA2A+ (0.63, 0.45-0.88, 0.04), in IAA and/or IA2A+ (0.52, 0.33-0.84, 0.044), and in IAA and IA2A+ (0.55, 0.39-0.78, 0.0055) patients when compared with patients negative for corresponding antibodies. Frequency of MICA9, 5/5.1, and 5.1/9 was decreased in IAA+ compared to IAA- patients (0.51, 0.32-0.79, 0.021; 0.22, 0.11-0.44, <0.005; and 0.39, 0.22-0.69, 0.026, respectively). Frequency of MICA9 and -5.1/9 was also decreased in IAA and/or IA2 antibody-positive patients while MICA5/5.1 decreased in patients positive for IAA and IA2 antibody both together. IAA and IA2 antibodies are believed to appear early during the autoimmune reaction against beta cells. Thus, according to our data, MICA-5/5 and -5.1/5.1 is associated with early autoimmunity in T1DM patients. Our study suggests that MICA gene polymorphism is associated with autoantibody formation and that the polymorphism especially MICA5/5 and -5.1/5.1 are important in early events of autoimmune reaction.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".