Cytomegalovirus immunity in high-risk liver transplant recipients following preemptive antiviral therapy versus prophylaxis

被引：3

作者：

Zamora, Danniel ^{[1
,2
]}

Dasgupta, Sayan ^{[2
]}

Stevens-Ayers, Terry ^{[2
]}

Edmison, Bradley ^{[2
]}

Winston, Drew J. ^{[3
]}

Razonable, Raymund R. ^{[4
]}

Mehta, Aneesh K. ^{[5
]}

Lyon, G. Marshall ^{[5
]}

Boeckh, Michael ^{[1
,2
]}

Singh, Nina ^{[6
,7
]}

Koelle, David M. ^{[1
,2
,8
,9
,10
]}

Limaye, Ajit P. ^{[1
,2
]}

机构：

[1] Univ Washington, Dept Med, Div Allergy & Infect Dis, Seattle, WA USA

[2] Fred Hutchinson Canc Ctr, Vaccine & Infect Dis Div, Seattle, WA USA

[3] UCLA Med Ctr, Div Infect Dis, Los Angeles, CA USA

[4] Mayo Clin, Div Publ Hlth Infect Dis & Occupat Med, Rochester, MN USA

[5] Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA USA

[6] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA

[7] VA Pittsburgh Healthcare Syst, Transplant Infect Dis, Pittsburgh, PA USA

[8] Univ Washington, Dept Global Hlth, Seattle, WA USA

[9] Univ Washington, Dept Lab Med & Pathol, Seattle, WA USA

[10] Benaroya Res Inst, Seattle, WA USA

来源：

JCI INSIGHT | 2024年 / 9卷 / 18期

关键词：

T-CELL RESPONSES; NEUTRALIZING ANTIBODIES; CMV DISEASE; ALLOGRAFT FAILURE; NK CELLS; INFECTION; VALGANCICLOVIR; RECONSTITUTION; KIDNEY; REACTIVATION;

D O I：

10.1172/jci.insight.180115

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

CMV-specific T cells, NK cells, and neutralizing antibodies (nAbs) were assessed in a randomized trial of CMV prevention with preemptive antiviral therapy (PET) versus prophylactic antiviral therapy (PRO) in donor-seropositive/recipient-seronegative (D+R-) liver transplant recipients (LTxR) at 100 days (end of intervention) and at 6 and 12 months after transplant. The PET group had significantly increased numbers of circulating polyfunctional T cells, NK cells, and nAbs compared with the PRO group at day 100, and several CMV immune parameters remained significantly higher by 12 months after transplant. Among PET recipients, preceding CMV viremia (vs. no preceding viremia) was associated with significantly higher levels of most CMV immune parameters at day 100. Higher numbers of CMV-specific polyfunctional T cells and NKG2C(+) NK cells at day 100 were associated with a decreased incidence of CMV disease in multivariable Cox regression. The strongest associations with protection against CMV disease were with increased numbers of CMV-specific polyfunctional CD4(+) T cells, CD3(neg)CD56(dim)CD57(neg)NKG2C(pos) cells, and CD3(neg)CD56(dim)CD57(pos)NKG2C(pos) NK cells. Our results suggest that PET is superior to PRO for CMV disease prevention by allowing low-level CMV replication and associated antigen exposure that is promptly controlled by antiviral therapy and facilitates enhanced CMV protective immunity in D+R- LTxR.

引用

页数：21

共 89 条

[1] Evaluation of Cytomegalovirus (CMV)-Specific T Cell Immune Reconstitution Revealed That Baseline Antiviral Immunity, Prophylaxis, or Preemptive Therapy but not Antithymocyte Globulin Treatment Contribute to CMV-Specific T Cell Reconstitution in Kidney Transplant Recipients [J].