Humoral immunity to memory antigens and pathogens is maintained in patients with chronic kidney disease.

Nadezhda A Wall,Sian E Faustini,Ian R Henderson,Matthew D Morgan,Adam F Cunningham,Marisol Perez-Toledo,Charles J Ferro,Lorraine Harper,Charlotte N Cook,C Coral Dominguez-Medina,Mark D Jesky,Paul Cockwell,Alexandra G Richter,Paul A Moss,Andrew Mcclean

doi:10.1371/journal.pone.0195730

Abstract

Patients with chronic kidney disease (CKD) have an increased risk of infection and poorer responses to vaccination. This suggests that CKD patients have an impaired responsiveness to all antigens, even those first encountered before CKD onset. To examine this we evaluated antibody responses against two childhood vaccine antigens, tetanus (TT) and diphtheria toxoids (DT) and two common pathogens, cytomegalovirus (CMV) and Salmonella enterica serovar Enteritidis (SEn) in two independent cohorts consisting of age-matched individuals with and without CKD. Sera were evaluated for antigen-specific IgG titres and the functionality of antibody to SEn was assessed in a serum bactericidal assay. Surprisingly, patients with CKD and control subjects had comparable levels of IgG against TT and DT, suggesting preserved humoral memory responses to antigens encountered early in life. Lipopolysaccharide-specific IgG titres and serum bactericidal activity in patients with CKD were also not inferior to controls. CMV-specific IgG titres in seropositive CKD patients were similar or even increased compared to controls. Therefore, whilst responses to new vaccines in CKD are typically lower than expected, antibody responses to antigens commonly encountered prior to CKD onset are not. The immunodeficiency of CKD is likely characterised by failure to respond to new antigenic challenges and efforts to improve patient outcomes should be focussed here.

Highlights

This study evaluates serological responses to several historical and persistent antigens in individuals with Chronic kidney disease (CKD) not requiring renal replacement therapy (RRT)
After vaccination against hepatitis B, seasonal influenza and pneumococcus, patients with severe CKD consistently show reduced peak antibody titres and poor response longevity when compared to healthy controls. [10, 12, 28] We show, in two independent cohorts consisting of age-matched healthy controls and individuals with CKD, that IgG responses to two common historical vaccine antigens (TT and diphtheria toxoids (DT)) are comparable in patients with CKD to that of healthy controls, both in terms of absolute values and levels deemed to confer protection against disease
Our findings suggest that the immune impairment seen in CKD is not universal to all antigens encountered across the life course of the individual, but may affect responses to antigens encountered more recently, when disease is established, rather than responses to antigens encountered earlier in life

Summary

Introduction

Chronic kidney disease (CKD) is an important global clinical problem and is defined and staged by measures of kidney function, the estimated glomerular filtration rate (eGFR), and kidney damage, primarily albuminuria. Chronic kidney disease and humoral immunity in the design of this study, data collection and analysis, decision to publish, or preparation of the manuscript

Methods

Results

Conclusion