Immunologic Aging in Adults with Congenital Heart Disease: Does Infant Sternotomy Matter?
Thymectomy is performed routinely in infants undergoing cardiothoracic surgery. Children post-sternotomy have decreased numbers of T lymphocytes, although the mechanisms involved and long-term consequences of this have not been defined. We hypothesized that lymphopenia in patients with adult congenital heart disease (ACHD) would be reflective of premature T cell maturation and exhaustion. Adults with ACHD who had sternotomy to repair congenital heart disease as infants (<1 year) and age-matched ACHD patients without prior sternotomy were studied using polychromatic flow cytometry interrogating markers of lymphocyte maturation, exhaustion and senescence. Group differences were analyzed using Mann-Whitney U and Fisher's exact tests. Eighteen ACHD patients aged 21-40 years participated: 10 cases and 8 controls. Median age at sternotomy for cases was 52 days. Cases and controls were matched for age (28.9 vs. 29.1 years; p = 0.83), gender (p = 0.15) and race (p = 0.62) and had similar case complexity. Cases had a lower mean percentage of cytotoxic CD8 lymphocytes compared to controls (26.8 vs. 33.9 %; p = 0.016), with fewer naive, undifferentiated CD8 T cells (31.0 vs. 53.6 %; p = 0.027). CD8 cells expressing PD1, a marker of immune exhaustion, trended higher in cases versus controls (25.6 vs. 19.0 %; p = 0.083). Mean percentage of CD4 cells was higher in cases versus controls (65.6 vs. 59.6 %; p = 0.027), without differences in CD4 T cell maturation subtype. In summary, ACHD patients who undergo sternotomy as infants exhibit differences in T lymphocyte composition compared to ACHD controls, suggesting accelerated immunologic exhaustion. Investigation is warranted to assess the progressive nature and clinical impact of this immune phenotypic change.
Section of Pediatric Cardiology, Department of Pediatrics and Internal Medicine, Yale University School of Medicine, PO Box 208064, 333 Cedar Street, 3 LCI, New Haven, CT, 06510, USA. robert.elder@yale.edu.
Robert W
RW
Elder
Department of Pediatric Nephrology, Emory University School of Medicine, 1405 Clifton Road, NE, Atlanta, GA, 30322, USA.
Roshan P
RP
George
Nell Hodgson Woodruff School of Nursing, Emory University, 1520 Clifton Road, NE, Atlanta, GA, 30322, USA.
Nancy M
NM
McCabe
Division of Pediatric Cardiology, Sibley Heart Center, Children's Healthcare of Atlanta, Emory University School of Medicine, 1405 Clifton Road, NE, Atlanta, GA, 30322, USA.
Fred H
FH
Rodriguez
Division of Cardiology, Department of Internal Medicine, Emory University School of Medicine, 1365 Clifton Road, NE, Suite A2447, Atlanta, GA, 30322, USA.
Wendy M
WM
Book
Division of Pediatric Cardiology, Sibley Heart Center, Children's Healthcare of Atlanta, Emory University School of Medicine, 1405 Clifton Road, NE, Atlanta, GA, 30322, USA.
William T
WT
Mahle
Department of Surgery, Duke University School of Medicine, DUMC 3704, Durham, NC, 27710, USA.
Allan D
AD
Kirk
D000328:Adult; D000375:Aging; D015415:Biomarkers / Q000097:blood*; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006330:Heart Defects, Congenital / Q000276:immunology* / Q000601:surgery; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010865:Pilot Projects; D011446:Prospective Studies; D056346:Sternotomy / Q000379:methods*; D013934:Thymectomy / Q000379:methods*; D055815:Young Adult
D015415:Biomarkers
Adult congenital heart disease; Congenital heart disease; Immune function; Surgery; Thymectomy