title: Correlation of immunological markers with graft vasculopathy development in heart transplantation.
abstract: This study examined the imbalance between T effector cells (Th1 defined as CD3+ interferonγ+) and T regulatory cells (Treg defined as CD4+CD25(high)FoxP3+) as a valuable albeit limited marker of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). CAV remains, with neoplasms, the most important cause of death in patients surviving the first year after HTx. It is an immune-mediated pathology, although nonimmune factors may also play a role. The process included concentric fibrous intima hyperplasia that narrows the entire length of the affected arteries. Coronary angiography is the usual method of diagnosis. Because a transplanted heart is a denervated organ, CAV is not diagnosed until the disease reaches an advanced stage, in which case transplantation is the only option for treatment. Although the host's immune response against an allogeneic graft is the major cause of endothelial dysfunction, the objective of this study was to detect anti-allogeneic responses on peripheral blood, seeking to identify signs of CAV before classical methods to predict outcomes in HTx recipients. CD3, CD4, CD8, CD19, CD56, Th1, and the Treg mononuclear cell populations were studied in 37 de novo and 20 long-term (more than 3 years) HTx patients as well as 20 healthy volunteers using flow cytometry. A progressive increase in CD8 and Th1 percentages and decrease in the CD4 population were detected during follow-up. Although Th1 changes also reflect processes not related to CAV receiver operating characteristics analysis of Th1/Treg ratio showed an area under the curve of 0.976, with an estimated sensitivity of 100% and specificity of 90%. The positive prediction value was 58.8% and the negative prediction value, 100%. These results prove that the Th1/Treg ratio was an important marker to following host immune response after HTx. The results confirm the need to test other T lymphocyte subsets.
authors.affiliation: Immunology Department, Hospital Sant. Pau, Barcelona, Spain. CRoldanf@santpau.cat
authors.forename: C
authors.initials: C
authors.lastname: Roldán
authors.forename: S
authors.initials: S
authors.lastname: Mirabet
authors.forename: V
authors.initials: V
authors.lastname: Brossa
authors.forename: E
authors.initials: E
authors.lastname: Moltó
authors.forename: L
authors.initials: L
authors.lastname: Lopez
authors.forename: Y
authors.initials: Y
authors.lastname: Alvaro
authors.forename: E
authors.initials: E
authors.lastname: Sole
authors.forename: J M
authors.initials: JM
authors.lastname: Padró
authors.forename: C
authors.initials: C
authors.lastname: Gelpí
authors.forename: E
authors.initials: E
authors.lastname: Roig
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D017252:CD3 Complex / Q000097:blood; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000097:blood; D016027:Heart Transplantation / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D012680:Sensitivity and Specificity; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D017252:CD3 Complex; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C573415:IFNG protein, human; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D007371:Interferon-gamma