Evaluation of humoral immunity profiles to identify heart recipients at risk for development of severe infections: A multicenter prospective study

J Heart Lung Transplant. 2017 May;36(5):529-539. doi: 10.1016/j.healun.2016.10.004. Epub 2016 Oct 17.

Abstract

Background: New biomarkers are necessary to improve detection of the risk of infection in heart transplantation. We performed a multicenter study to evaluate humoral immunity profiles that could better enable us to identify heart recipients at risk of severe infections.

Methods: We prospectively analyzed 170 adult heart recipients at 8 centers in Spain. Study points were before transplantation and 7 and 30 days after transplantation. Immune parameters included IgG, IgM, IgA and complement factors C3 and C4, and titers of specific antibody to pneumococcal polysaccharide antigens (anti-PPS) and to cytomegalovirus (CMV). To evaluate potential immunologic mechanisms leading to IgG hypogammaglobulinemia, before heart transplantation we assessed serum B-cell activating factor (BAFF) levels using enzyme-linked immunoassay. The clinical follow-up period lasted 6 months. Clinical outcome was need for intravenous anti-microbials for therapy of infection.

Results: During follow-up, 53 patients (31.2%) developed at least 1 severe infection. We confirmed that IgG hypogammaglobulinemia at Day 7 (defined as IgG <600 mg/dl) is a risk factor for infection in general, bacterial infections in particular, and CMV disease. At Day 7 after transplantation, the combination of IgG <600 mg/dl + C3 <80 mg/dl was more strongly associated with the outcome (adjusted odds ratio 7.40; 95% confidence interval 1.48 to 37.03; p = 0.014). We found that quantification of anti-CMV antibody titers and lower anti-PPS antibody concentrations were independent predictors of CMV disease and bacterial infections, respectively. Higher pre-transplant BAFF levels were a risk factor of acute cellular rejection.

Conclusion: Early immunologic monitoring of humoral immunity profiles proved useful for the identification of heart recipients who are at risk of severe infection.

Keywords: complement; heart transplantation; hypogammaglobulinemia; infection; risk factors.

Publication types

  • Evaluation Study
  • Multicenter Study

MeSH terms

  • Adult
  • B-Cell Activating Factor / blood
  • Bacterial Infections / epidemiology
  • Bacterial Infections / physiopathology
  • Biomarkers / blood
  • Cohort Studies
  • Complement C3 / metabolism
  • Complement C4 / metabolism
  • Cytomegalovirus Infections / epidemiology*
  • Cytomegalovirus Infections / etiology
  • Cytomegalovirus Infections / physiopathology
  • Female
  • Graft Rejection / immunology
  • Heart Transplantation / adverse effects*
  • Heart Transplantation / methods
  • Humans
  • Immunity, Humoral / physiology*
  • Immunoglobulins / blood*
  • Immunoglobulins / immunology
  • Incidence
  • Kaplan-Meier Estimate
  • Logistic Models
  • Male
  • Middle Aged
  • Monitoring, Immunologic / methods
  • Multivariate Analysis
  • Postoperative Complications / blood
  • Postoperative Complications / diagnosis*
  • Prognosis
  • Prospective Studies
  • ROC Curve
  • Risk Assessment
  • Spain
  • Virus Diseases / epidemiology
  • Virus Diseases / physiopathology

Substances

  • B-Cell Activating Factor
  • Biomarkers
  • Complement C3
  • Complement C4
  • Immunoglobulins