Enhanced Immune Function and Pro-Inflammatory Cytokines in Highly Sensitized Patients Awaiting Kidney Transplantation
Bibliographic record
Abstract
Introduction: In kidney transplantation, highly sensitized patients (HSP) have inferior outcomes compared to non-sensitized patients (NSP) due to high levels of circulating anti-HLA antibodies. Little is known about the pre-transplant global immune function and cytokine profile of HSP. An altered immune function and cytokine profile could participate in creating or maintaining circulating antibodies. We compared global immune function, leukocyte cytokine secretion, memory B cells, and regulatory T and B cells between HSP and NSP. Methods: Peripheral blood was collected from 27 patients on the kidney transplant waiting list prior to hemodialysis. HSP (n=15, age=54±3, M/F=6/9) were defined as patients with a panel reactive antibody (PRA) above 70% while NSP (n=12, age=58±4, M/F=11/1) had a PRA below 1%. In 15 HSP and 12 NSP, global immune function was quantified using the ImmuKnow® assay (Cylex Inc., Columbia, MD, USA). In 10 HSP and 11 NSP, enzyme-linked immunosorbent assay was performed on the ImmuKnow® assay supernatant to measure IL-17 secretion. In 7 HSP and 7 NSP, frequency of leukocyte cytokine secretion, memory B cells, and regulatory T and B cells was measured by flow cytometry. Statistical analysis was performed with Student's t-test. Results: Global immune function and IL-17 secretion were significantly higher in HSP than NSP (p=0.05, Fig. 1A and p< 0.01, Fig. 1B respectively). Frequency of CD14+ monocytes, CD11c+ dendritic, CD56+ NK, CD4+ T, and CD19+ B cells was similar between HSP and NSP. However, frequency of IL-17+ CD14+ monocytes, IL-17+ CD11c+ dendritic cells, IFN-γ+, IL-4+, IL-17+, and IL-6+ CD4+ T cells, and IFN-γ+ CD19+ B cells was significantly higher in HSP (p≤0.05). Frequency of memory CD27+ CD19+ B cells was also higher in HSP (p=0.03, Fig. 1C). There was no difference in FoxP3+ regulatory CD4+ T cells or IL-10+ CD19+ regulatory B cells.[Figure 1]Conclusion: HSP awaiting kidney transplantation have a higher global immune function, increased pro-inflammatory cytokine secretion by leukocytes, and increased frequency of memory B cells in comparison to NSP without a compensatory regulatory response. These findings reinforce the use of B and T cells blockade or depletion in pre-emptive desensitization protocols and suggest that the addition of pro-inflammatory cytokines blockade in these protocols could further improve post-transplant outcomes in HSP.
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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 | 0.001 |
| 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".