PMID- 26967790
OWN - NLM
STAT- MEDLINE
DCOM- 20170719
LR  - 20220330
IS  - 1535-4970 (Electronic)
IS  - 1073-449X (Linking)
VI  - 194
IP  - 5
DP  - 2016 Sep 1
TI  - De Novo DQ Donor-Specific Antibodies Are Associated with Chronic Lung Allograft 
      Dysfunction after Lung Transplantation.
PG  - 596-606
LID - 10.1164/rccm.201509-1857OC [doi]
AB  - RATIONALE: Despite increasing evidence about the role of donor-specific human 
      leukocyte antigen (HLA) antibodies in transplant outcomes, the incidence and 
      impact of de novo donor-specific antibodies (dnDSA) after lung transplantation 
      remains unclear. OBJECTIVES: To describe the incidence, characteristics, and 
      impact of dnDSA after lung transplantation. METHODS: We investigated a 
      single-center cohort of 340 lung transplant recipients undergoing transplant 
      during 2008 to 2011. All patients underwent HLA-antibody testing quarterly 
      pretransplant and at regular intervals over the first 24 months after transplant. 
      The patients received modified immunosuppression depending on their pretransplant 
      sensitization status. Risk factors for dnDSA development, as well as the 
      associations of dnDSA with patient survival and chronic lung allograft 
      dysfunction (CLAD), were determined using multivariable analysis. MEASUREMENTS 
      AND MAIN RESULTS: The cumulative incidence of dnDSA was 47% at a median of 86 
      days (range, 44-185 d) after lung transplantation. Seventy-six percent of 
      recipients with dnDSA had DQ-DSA. Male sex and the use of ex vivo lung perfusion 
      were associated with an increased risk of dnDSA, whereas increased HLA-DQB1 
      matching was protective. DQ-dnDSA preceded or coincided with the diagnosis of 
      CLAD in all cases. Developing dnDSA (vs. no dnDSA) was associated with a twofold 
      increased risk of CLAD (hazard ratio, 2.04; 95% confidence interval, 1.13-3.69). 
      This association appeared to be driven by the development of DQ-dnDSA. 
      CONCLUSIONS: dnDSA are common after lung transplantation, with the majority being 
      DQ DSA. DQ-dnDSA are associated with an increased risk of CLAD. Strategies to 
      prevent or treat DQ-dnDSA may improve outcomes for lung transplant recipients.
FAU - Tikkanen, Jussi M
AU  - Tikkanen JM
AD  - 1 Toronto Lung Transplant Program.
FAU - Singer, Lianne G
AU  - Singer LG
AUID- ORCID: 0000-0002-2693-8676
AD  - 1 Toronto Lung Transplant Program.
FAU - Kim, S Joseph
AU  - Kim SJ
AD  - 2 Division of Nephrology, Department of Medicine, and.
FAU - Li, Yanhong
AU  - Li Y
AD  - 2 Division of Nephrology, Department of Medicine, and.
FAU - Binnie, Matthew
AU  - Binnie M
AD  - 1 Toronto Lung Transplant Program.
FAU - Chaparro, Cecilia
AU  - Chaparro C
AD  - 1 Toronto Lung Transplant Program.
FAU - Chow, Chung-Wai
AU  - Chow CW
AD  - 1 Toronto Lung Transplant Program.
FAU - Martinu, Tereza
AU  - Martinu T
AD  - 1 Toronto Lung Transplant Program.
FAU - Azad, Sassan
AU  - Azad S
AD  - 1 Toronto Lung Transplant Program.
FAU - Keshavjee, Shaf
AU  - Keshavjee S
AD  - 1 Toronto Lung Transplant Program.
FAU - Tinckam, Kathryn
AU  - Tinckam K
AD  - 2 Division of Nephrology, Department of Medicine, and.
AD  - 3 HLA Laboratory, Laboratory Medicine Program, Toronto General Hospital, 
      University Health Network, Toronto, Ontario, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Respir Crit Care Med
JT  - American journal of respiratory and critical care medicine
JID - 9421642
RN  - 0 (HLA Antigens)
RN  - 0 (Immunosuppressive Agents)
SB  - IM
CIN - Am J Respir Crit Care Med. 2016 Sep 1;194(5):534-5. PMID: 27585379
MH  - Allografts/*immunology/statistics & numerical data
MH  - Bronchiolitis Obliterans/epidemiology/etiology/*immunology
MH  - Female
MH  - Graft Rejection/complications/epidemiology/*immunology
MH  - HLA Antigens/*immunology
MH  - Humans
MH  - Immunosuppressive Agents/administration & dosage
MH  - Kaplan-Meier Estimate
MH  - Lung/*immunology
MH  - Lung Transplantation/*adverse effects/statistics & numerical data
MH  - Male
MH  - Middle Aged
MH  - Ontario/epidemiology
MH  - Proportional Hazards Models
MH  - Retrospective Studies
MH  - Sex Distribution
MH  - *Tissue Donors
OTO - NOTNLM
OT  - bronchiolitis obliterans syndrome
OT  - chronic lung allograft dysfunction
OT  - donor-specific antibodies
OT  - lung transplantation
EDAT- 2016/03/12 06:00
MHDA- 2017/07/20 06:00
CRDT- 2016/03/12 06:00
PHST- 2016/03/12 06:00 [entrez]
PHST- 2016/03/12 06:00 [pubmed]
PHST- 2017/07/20 06:00 [medline]
AID - 10.1164/rccm.201509-1857OC [doi]
PST - ppublish
SO  - Am J Respir Crit Care Med. 2016 Sep 1;194(5):596-606. doi: 
      10.1164/rccm.201509-1857OC.