The Incidence of Class II DSA According to Mismatched Alleles Is Affected by Calcineurin Inhibitor Drug Levels
Bibliographic record
Abstract
Introduction: Donor specific antibodies (DSA) to mismatched HLA class II antigens remain a barrier to long term kidney graft survival. We investigated the relationship of de novo class II DSA generation calcineurin inhibitor (CNI) levels, and graft survival in kidney transplantation. Methods: Class II DSA and CNI (tacrolimus (TAC), cyclosporin (CS)) levels were compared in 472 kidney transplant recipients undergoing DSA testing post-transplant. Patients were subdivided into three groups according to CNI levels measured within the year prior to the time of DSA testing: Normal - TAC>4/CS>75 (N=299), Low - TAC=3-4/CS=50-75 (N=86), Very Low - TAC< 3/CS< 50 (N=87). The incidence of DSA was calculated for each class II locus (HLA-DRB1, -DRB3/4/5, and -DQB1) as a percent of the times that locus was mismatched in each group. DSA to DRB1 in patients with Low or Very Low CNI levels were combined due to the low number of these antibodies in the Low CNI group. Results: As a percent of the number of mismatched antigens, the highest incidence of DSA in this patient population was against DQ7/8/9, followed by DQ2, DQ4, DQ5/6, DRB3/4/5, and DRB1 DSA (Figure 1). The highest incidence of DSA was observed in patients with very low CNI levels who developed DSA against DQ7/8/9 56.7% of the time these antigens were mismatched. The incidence of DQ7/8/9 and DQ4 DSA dramatically decreased with increasing CNI levels whereas DQ2 DSA and DQ5/6 DSA decreased modestly. The incidence of DSA to HLA-DR loci did not change with CNI levels.[FIGURE 1]We also examined the effect of DSA specificities on graft loss. The incidence of DSA to the class II loci indicated above was repeated but only including patients who had lost their grafts (N=103). Within this cohort the incidence of DSA was again highest for DQ7/8/9 DSA (61.8%), followed by DQ2, DQ5/6, DQ4, DRB1, and DRB3/4/5 (Table 1).[TABLE 1. DSA IN PATIENTS WITH GRAFT LOSS]Conclusion: Our data suggest that higher CNI levels may help decrease the incidence of class II DSA to certain mismatched loci and also lower the increased risk of graft loss. Further work may allow for target CNI levels to be customized for kidney transplant patients based on mismatched donor HLA class II antigens.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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) | 0.002 | 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".