Purpose <p>This study aimed to determine the relation between CD38+ B-cell infiltration and outcome of transplant recipients diagnosed with chronic active antibody mediated rejection (caABMR).</p> Methods <p>A total of 67 patients transplanted from April 2003 and July 2021 with biopsy-proved caABMR were included. The density of CD3+ , CD20+ and CD38+ cells were quantified by immunohistochemical staining and baseline information, estimated glomerular filtration rate (eGFR) and 24 h urine quantitative protein at diagnose were collected. Receiver operating characteristic (ROC) curves were used to calculate the cut-off values in the prediction of graft loss and prognosis factors were further analyzed by Cox proportional-hazards analysis. Kaplan–Meier death-censored graft survivals of subgroups divided by CD38+ B-cell infiltration or urine quantitative protein were compared.</p> Results <p>The median density of CD3+ , CD20+ and CD38+ cells was 278, 167 and 89 (per mm<sup>2</sup>). CD38+ B cell infiltration in biopsies was associated with graft survival and the cut-off value was ≥ 93/mm<sup>2</sup> with 92.90% sensitivity, 66.00% specificity, the cut-off values of 24-h urine quantitative protein and eGFR were ≥ 1.85&#xa0;g and ≤ 29.50&#xa0;ml/min*1.73m<sup>2</sup> correspondingly, with 85.70%, 85.60% sensitivity, 64.20%, 74.90% specificity. Cox proportional-hazards analysis showed that the increase of CD38+ B cell infiltration and urine protein were independent risk factors and eGFR was a protective factor for caABMR with the hazard ratios of 1.96 (95%CI 1.03–3.72, <i>P</i> = 0.040), 1.24 (95%CI 1.01–1.52, <i>P</i> = 0.042) and 0.94 (95%CI 0.89–0.99, <i>P</i> = 0.025) correspondingly. Kaplan–Meier survival analysis demonstrated that patients with CD38+ B-cell infiltration ≥ 93/mm<sup>2</sup> or 24-h urine protein ≥ 1.85&#xa0;g had significantly reduced graft survival (<i>P</i> &lt; 0.01).</p> Conclusion <p>A threshold of CD38+ B cell infiltration ≥ 93/mm<sup>2</sup> was associated with poor graft survival and CD38 might be a potential therapeutic target of caABMR.</p>

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The effects of intragraft CD38+ B cell on chronic active antibody mediated rejection in kidney transplantation

  • Yu Hui,
  • Linkun Hu,
  • Liangliang Wang,
  • Xuedong Wei,
  • Yuhua Huang,
  • Jianquan Hou

摘要

Purpose

This study aimed to determine the relation between CD38+ B-cell infiltration and outcome of transplant recipients diagnosed with chronic active antibody mediated rejection (caABMR).

Methods

A total of 67 patients transplanted from April 2003 and July 2021 with biopsy-proved caABMR were included. The density of CD3+ , CD20+ and CD38+ cells were quantified by immunohistochemical staining and baseline information, estimated glomerular filtration rate (eGFR) and 24 h urine quantitative protein at diagnose were collected. Receiver operating characteristic (ROC) curves were used to calculate the cut-off values in the prediction of graft loss and prognosis factors were further analyzed by Cox proportional-hazards analysis. Kaplan–Meier death-censored graft survivals of subgroups divided by CD38+ B-cell infiltration or urine quantitative protein were compared.

Results

The median density of CD3+ , CD20+ and CD38+ cells was 278, 167 and 89 (per mm2). CD38+ B cell infiltration in biopsies was associated with graft survival and the cut-off value was ≥ 93/mm2 with 92.90% sensitivity, 66.00% specificity, the cut-off values of 24-h urine quantitative protein and eGFR were ≥ 1.85 g and ≤ 29.50 ml/min*1.73m2 correspondingly, with 85.70%, 85.60% sensitivity, 64.20%, 74.90% specificity. Cox proportional-hazards analysis showed that the increase of CD38+ B cell infiltration and urine protein were independent risk factors and eGFR was a protective factor for caABMR with the hazard ratios of 1.96 (95%CI 1.03–3.72, P = 0.040), 1.24 (95%CI 1.01–1.52, P = 0.042) and 0.94 (95%CI 0.89–0.99, P = 0.025) correspondingly. Kaplan–Meier survival analysis demonstrated that patients with CD38+ B-cell infiltration ≥ 93/mm2 or 24-h urine protein ≥ 1.85 g had significantly reduced graft survival (P < 0.01).

Conclusion

A threshold of CD38+ B cell infiltration ≥ 93/mm2 was associated with poor graft survival and CD38 might be a potential therapeutic target of caABMR.