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. 2023 Jul 11:14:1192440.
doi: 10.3389/fimmu.2023.1192440. eCollection 2023.

Pre-transplant immune profile defined by principal component analysis predicts acute rejection after kidney transplantation

Emilie Gaiffe  1   2 , Mathilde Colladant  2   3 , Maxime Desmaret  1   2 , Jamal Bamoulid  2   3 , Franck Leroux  1 , Caroline Laheurte  2 , Sophie Brouard  4 , Magali Giral  4 , Philippe Saas  2 , Cécile Courivaud  2   3 , Nicolas Degauque  4 , Didier Ducloux  1   2   3
Affiliations

Pre-transplant immune profile defined by principal component analysis predicts acute rejection after kidney transplantation

Emilie Gaiffe et al. Front Immunol. .

Abstract

Background: Acute rejection persists as a frequent complication after kidney transplantation. Defining an at-risk immune profile would allow better preventive approaches.

Methods: We performed unsupervised hierarchical clustering analysis on pre-transplant immunological phenotype in 1113 renal transplant recipients from the ORLY-EST cohort.

Results: We identified three immune profiles correlated with clinical phenotypes. A memory immune cluster was defined by memory CD4+T cell expansion and decreased naïve CD4+T cell. An activated immune cluster was characterized by an increase in CD8+T cells and a decreased CD4/CD8 ratio. A naïve immune cluster was mainly defined by increased naïve CD4+T cells. Patients from the memory immune profile tend to be older and to have diabetes whereas those from the activated immune profile were younger and more likely to have pre-transplant exposure to CMV. Patients from the activated immune profile were more prone to experience acute rejection than those from other clusters [(HR=1.69, 95%IC[1.05-2.70], p=0.030) and (HR=1.85; 95%IC[1.16-3.00], p=0.011). In the activated immune profile, those without previous exposure to CMV (24%) were at very high risk of acute rejection (27 vs 16%, HR=1.85; 95%IC[1.04-3.33], p=0.039).

Conclusion: Immune profile determination based on principal component analysis defines clinically different sub-groups and discriminate a population at high-risk of acute rejection.

Keywords: acute rejection; biomarker; hierarchical clustering analysis; immune profile; kidney transplantation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Patient flow chart.
Figure 2
Figure 2
Hierarchical clustering of patients after principal component analysis (A) represented by the dendrogram of patients and (B) by a scatter view plot. (A) identification of 3 clusters among 832 first transplant recipients according to immunological data. Profiles were assigned based on the separation of the clustering trees. (B) Colors were based on clustering profile and mainly defined by dimension 2 and dimension 1 in our hierarchical clustering. Three clusters were identified: older immunity in red (cluster 1), activated immunity in green (cluster 2) and naïve immunity in blue (cluster 3).
Figure 3
Figure 3
Kaplan Meier curves for survival without acute rejection according to cluster belinging. Three clusters were identified: memory immunity in red (cluster 1), activated immunity in green (cluster 2) and naïve immunity in blue (cluster 3).
Figure 4
Figure 4
Competitive risk of death and acute rejection at 1 years post transplantation according to clusters determined with principal component analysis identified as older immunity (cluster 1), activated immunity (cluster 2) and naïve immunity (cluster 3). Three clusters were identified: memory immunity with full line (cluster 1), activated immunity with dashed line (cluster 2) and naïve immunity with dotted line (cluster 3).
Figure 5
Figure 5
Kaplan Meier curves for survival without acute rejection according to patients CMV status of cluster 2 (activated immunity). Patients naïve to CMV exposure were identified with full line and patient exposed to CMV with dashed line.
See this image and copyright information in PMC

References

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