Deep immune profiling of patients with renal impairment unveils distinct immunotypes associated with disease severity.

Abstract

Chronic kidney disease (CKD) is pathologically correlated with a sophisticated milieu of innate and adaptive immune dysregulation, but the underlying immunological disturbances remain poorly understood. To address this, we comprehensively interrogated cellular and soluble elements of the immune system by using high-dimensional flow cytometry to analyze peripheral blood mononuclear cells and performing cytokine/chemokine profiling of serum samples, respectively, in a cohort of 69 patients and 19 non-CKD controls. Altered serum levels of several cytokines/chemokines were identified, among which concentrations of stem cell factor (SCF) were found to be elevated with the progression of CKD and inversely correlated with estimated glomerular filtration rate (eGFR). Deep immunophenotyping analyses reveal a global change in immune modulation associated with CKD severity. Specifically, a decrease in the subsets of CD56dim natural killer (NK) cells (KLRG-1+CD38+CD64+CD15+CD197+) and monocytes (KLRG-1+CD38+PD-1+) was detected in severe CKD compared with controls and mild CKD. In addition, comparisons between mild and severe CKD demonstrated a loss of a mature B cell population (PD-1+CD197+IgD+HLA-DR+) in the advanced stages of disease. Further, we identified immunophenotypic markers to discriminate mild CKD from the controls, among which the portion of CD38+ monocytes was of particular value in early diagnosis. Our data unveil severity-specific immunological signatures perturbed in CKD patients.