Synergistic Effect of HLA Eplet Mismatch Load and CMV Viremia on Clinical Antibody-Mediated Rejection in Lung Transplantation

Y. Im¹, S. Yeramaneni², Y. Yim³, J. Dodderer⁴, M. Askar¹, H. J. Huang⁵

¹Baylor University Medical Center, Dallas, TX, ²Baylor Scott & White Health, Dallas, TX, ³Ross University School of Medicine, Portsmouth, Dominica, ⁴Texas Tech University Health Sciences Center, El Paso, TX, ⁵Houston Methodist Hospital, Houston, TX

Meeting: 2019 American Transplant Congress

Abstract number: C341

Keywords: Cytomeglovirus, Lung transplantation, Major histocompatibility complex (MHC), Rejection

Session Information

Session Name: Poster Session C: Lung: All Topics

Session Type: Poster Session

Date: Monday, June 3, 2019

Session Time: 6:00pm-7:00pm

Presentation Time: 6:00pm-7:00pm

Location: Hall C & D

*Purpose: De novo donor specific antibodies (dnDSA) occur in up to 50% of lung transplant (LUTX) recipients within one year and are associated with increased risk for antibody-mediated rejection (AMR). HLA eplet mismatch is a risk factor for dnDSA development; however not all patients with dnDSA progress to AMR. We hypothesize cytomegalovirus (CMV) viremia in the setting of increased HLA eplet mismatch (MM) load exerts a synergistic effect on risk for AMR.

*Methods: HLA typing was performed using low resolution rSSO Luminex assay. HLAMatchmaker was used to compute Class I and II HLA Eplet MM load. HLA antibody testing by SAB was performed at evaluation, LUTX, and post-TX surveillance and clinical time points. CMV mismatch and R+ recipients received prophylaxis with ganciclovir or valganciclovir. Patients who developed CMV disease or viremia detected by PCR were considered CMV+. Primary endpoint was defined as AMR precipitating clinical intervention. Secondary endpoints included dnDSA and all-cause mortality at 1 year.

*Results: 126 adult patients underwent LUTX at Baylor University Medical Center between June 2013 and December 2016; 9 were excluded from the analysis for re-transplant (n=1), death within 30 days (n=4), incomplete HLA testing (n=3), and CMV viremia detected before TX (n=1). Of the 117 patients included, 42 (36%) were CMV+ and 75 (64%) were CMV-. Clinical AMR developed in 14/42 (33%) CMV+ and 9/75 (12%) CMV- patients. Patients in the AMR+ group had a higher Class II HLA Eplet MM load (27 vs 22; p=0.01) and developed dnDSA earlier (mean 330 vs 612 days; p=0.01). Also, development of AMR was associated with increased risk for mortality at 1 year (OR 4.94; p=0.001). When stratified by CMV status, Class II HLA Eplet MM was associated with increased risk for AMR (Tables 1 and 2).

Univariate OR predicting AMR stratified by CMV Viremia (per 1 MM)
CMV	Eplet	OR	95% CI	p-Value
POS	Class I	0.96	0.87 – 1.06	0.42
POS	Class II	1.08	1.00 – 1.17	0.04
POS	Class I+II	1.04	0.98 – 1.10	0.22
NEG	Class I	1.04	0.92 – 1.18	0.54
NEG	Class II	1.04	0.97 – 1.11	0.31
NEG	Class I+II	1.04	0.98 – 1.10	0.23

Univariate OR predicting AMR stratified by CMV Viremia (per 5 MM)
CMV	Eplet	OR	95% CI	p-Value
POS	Class I	0.81	0.49 – 1.34	0.42
POS	Class II	1.48	1.00 – 2.19	0.04
POS	Class I+II	1.20	0.90 – 1.62	0.22
NEG	Class I	1.22	0.65 – 2.31	0.54
NEG	Class II	1.20	0.85 – 1.68	0.31
NEG	Class I+II	1.19	0.90 – 1.59	0.23

*Conclusions: CMV viremia in the setting of high Class II HLA Eplet mismatch load increases risk for developing clinical AMR in lung transplant recipients.

To cite this abstract in AMA style:

Im Y, Yeramaneni S, Yim Y, Dodderer J, Askar M, Huang HJ. Synergistic Effect of HLA Eplet Mismatch Load and CMV Viremia on Clinical Antibody-Mediated Rejection in Lung Transplantation [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/synergistic-effect-of-hla-eplet-mismatch-load-and-cmv-viremia-on-clinical-antibody-mediated-rejection-in-lung-transplantation/. Accessed May 16, 2025.

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