Multi-Institutional Study of Anti-Nephrin Autoantibodies in Post-Transplant Focal Segmental Glomerulosclerosis Recurrence
Bibliographic record
Abstract
Background: Post-transplant recurrence of focal segmental glomerulosclerosis (rFSGS) is a major challenge in kidney transplantation. Recently, we reported very early pathological changes in podocytes and possible roles of circulating anti-nephrin antibodies (abs) in a patient with rFSGS (Hattori et al, Am J Transplant, 2022). To confirm these preliminary results, we performed a multi-institutional study. Methods: 14 Japanese kidney transplant recipients with childhood-onset primary FSGS who had stored plasma samples and graft biopsy specimens were analyzed. All patients underwent whole exome sequencing and no pathogenic variants in FSGS-related genes were identified. Circulating anti-nephrin abs were measured by ELISA and the cut off levels were defined as 231 U/mL, the maximum antibody levels among the controls (9 genetic FSGS patients, 13 membranous nephropathy patients, 4 lupus nephritis patients and 13 healthy controls). Dual immunofluorescence staining of nephrin and IgG or ShcA, an adaptor protein of phosphorylated nephrin, was performed using the structured illumination microscopy. Results: There were 10 rFSGS and 4 non-recurrent (non-rFSGS) patients. In rFSGS patients, median (interquartile range) anti-nephrin abs before transplant or during a posttransplant recurrence were markedly high at 950 (839, 1323) U/mL. Graft biopsies showed punctate IgG deposition co-localizing with nephrin that showed altered localization and increased expressions of ShcA. Eight of 10 rFSGS patients achieved remission, and graft biopsies after remission showed normal nephrin expression and no signals for IgG and ShcA. Anti-nephrin abs decreased to 261 (121, 398) U/mL in 4 patients with available samples at remission. In non-rFSGS patients, anti-nephrin abs were comparable with the controls regardless of the timing of sample collection. Their graft biopsies showed normal nephrin expression and no signals for IgG and ShcA. Conclusions: Our results suggest that anti-nephrin abs are associated with rFSGS via nephrin phosphorylation. Larger studies including other ethnicities are required to confirm this finding and to determine the prevalence and incidence of post-transplant FSGS recurrence associated with anti-nephrin abds. Funding: Government Support - Non-U.S.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".