title: Evaluation of an immunological score to assess the risk of severe infection in heart recipients.
abstract: BACKGROUND
  We previously reported how specific humoral and cellular immunological markers that are readily available in clinical practice can be used to identify heart transplant recipients (HTR) at risk of developing severe infections. In this study, we perform an extended analysis to identify immunological profiles that could prove to be superior to individual markers in assessing the risk of infection early after heart transplantation.
  
  
  METHODS
  In a prospective follow-up study, we evaluated 100 HTR at 1 week after transplantation. Laboratory tests included determination of immunoglobulin (Ig) levels (IgG, IgA, IgM), complement factors (C3 and C4), and lymphocyte subsets (CD3+, CD4+, CD8+ T cells, B cells, and natural killer [NK] cells). The prevalence of infection during the first 3 months was registered at scheduled visits after transplantation. Severe infections were defined as all infections requiring hospitalization and intravenous antimicrobial therapy.
  
  
  RESULTS
  During follow-up, 33 patients (33%) developed severe infections. The individual risk factors of severe infection, according to the Cox regression analysis, were as follows: IgG <600 mg/dL (hazard ratio [HR], 2.41; 95% confidence interval [CI], 1.21-4.78; P = 0.012), C3 <80 mg/dL (HR, 4.65; 95% CI, 2.31-9.38; P < 0.0001), C4 <18 mg/dL (HR 2.30, 95% CI, 1.15-4.59; P = 0.018), NK count <30 cells/μL (HR 4.07, 95% CI, 1.76-9.38; P = 0.001), and CD4 count <350 cells/μL (HR, 3.04; 95% CI, 1.47-6.28; P = 0.0027). An immunological score was created. HRs were used to determine the number of points assigned to each of the 5 previously mentioned individual risk factors. The score was obtained from the sum of these factors. In the multivariate Cox regression analysis, the immunological score was useful for identifying patients at risk of infection and was the only variable that maintained a significant association with the development of infection, after adjustment for the 5 individual factors.
  
  
  CONCLUSIONS
  Patients with an immunological score ≥13 were at the highest risk of severe infections (HR, 9.29; 95% CI, 4.57-18.90; P < 0.0001). This score remained significantly associated with the risk of severe infection after adjustment for clinical risk factors of infection. An immunological score was useful for identifying HTR at risk of developing severe infections. If this score is validated in multicenter studies, it could be easily introduced into clinical practice.
authors.affiliation: Clinical Immunology Department, University Hospital Gregorio Marañon, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Sarmiento
authors.forename: J
authors.initials: J
authors.lastname: Navarro
authors.forename: J
authors.initials: J
authors.lastname: Fernandez-Yañez
authors.forename: J
authors.initials: J
authors.lastname: Palomo
authors.forename: P
authors.initials: P
authors.lastname: Muñoz
authors.forename: J
authors.initials: J
authors.lastname: Carbone
mesh_terms: D000368:Aged; D001402:B-Lymphocytes; D001424:Bacterial Infections / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes; D003176:Complement C3 / Q000378:metabolism*; D003181:Complement C4 / Q000378:metabolism*; D003586:Cytomegalovirus Infections / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology; D006331:Heart Diseases / Q000601:surgery; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007111:Immunity, Cellular; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007136:Immunoglobulins / Q000097:blood*; D007239:Infections / Q000276:immunology*; D007694:Killer Cells, Natural; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000276:immunology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D003176:Complement C3; D003181:Complement C4; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins
keywords: C3; C4; CD4; IgG; NK cell; heart transplantation; immune monitoring; infection; risk factors; score