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Abstract

Introduction

Antibody (DSA) after lung transplantation (LuT) has been observed frequently with de novo Non-DSA (dN-DSA) HLA antibody. This study investigates the deleterious role of post-LuT NHAuAb and dN-DSA synergism to DSA in allograft damage.

Methods

We retrospectively analyzed NHAuAb and de novo DSA (dDSA)/dN-DSA data collected from the recipients who underwent LuT during 2012-2016. NHAuAbs were detected using LABScreenTM Autoantibody (>95% non-sensitized subjects as cut-off). HLA antibody was tested by LABScreenTM SAB (MFI≥ 1000 as cut-off). Clinical Antibody Mediated Rejection (cAMR, with acute graft dysfunction) and Chronic Lung Allograft Dysfunction (CLAD) were assessed for LuT outcomes. Results: CXCL9, AURKA, REG3A, IFNg, FLRT2, GDNF, HNRNPK, CXCL10, PLA2R, andCollagen IV detected from 111 patients’ sera drawn at DSA peak phase showed significant association to total AMR, but only FLRT2 (P<0.001), GDNF, and CXCL10 (P<0.05) were remarkably correlated to cAMR (Table 1a). Preformed & persistent LG3, PECR, PKC-Z (P<0.001) and de novo ENO1, GAPDH, Lamin-B, TubulinA1B (p<0.05) identified from 113 patients’ sera drawn around CLAD time, demonstrated strong correlation to the occurrence of CLAD (Table 1b). Patients with dDSA & dN-DSA had significantly higher incidence of cAMR than the patients with only dDSA (p<0.001, Table 1c).

Conclusion

Distinct clinical phases presented specific NHAuAb prof iles. Multiple NHAuAbs, especially LG3, PKC-Z, and PECR which were preformed & persistent, promoted chronic graft dysfunction. HLA-dDSA augmented by dN-DSA (most likely through shared targeting epitopes) and NHAuAbs of FLRT2, GDNF, and CXCL10 were related to acute graft injury. These HLA and non-HLA humoral risk factors warrant timely enhanced immune therapy to prevent final allograft failure.

Quelle

Vasileva A, Hanafi N, Matelski J, Wu J, DeHaas E, Huang Q, et al. Intra-Subject Variance of Respiratory Oscillometry Reflects Graft Injury and is Associated with Acute Rejection and Chronic Lung Allograft Dysfunction (CLAD) Post Lung Transplant (LTx). J Hear Lung Transplant [Internet]. 2021 Apr 1 [cited 2021 Mar 22];40(4):S57

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