Kidney Week

Abstract: FR-PO456

Markers of the Adaptive Immune Response Are Associated with Advancing CKD Status

Session Information

• CKD: Risk Factors for Incidence and Progression - II
  November 03, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Chronic Kidney Disease (Non-Dialysis)

• 301 CKD: Risk Factors for Incidence and Progression

Authors

• Crawford, Dana C, Case Western Reserve University, Cleveland Heights, Ohio, United States

Dana C Crawford,

• Bush, William S, Case Western Reserve University, Cleveland Heights, Ohio, United States

William S Bush,

• Cooke Bailey, Jessica N, Case Western Reserve University, Cleveland Heights, Ohio, United States

Jessica N Cooke Bailey,

• O'Toole, John F., Case Western Reserve University, Cleveland Heights, Ohio, United States

John F. O'Toole,

• Sedor, John R., Case Western Reserve University, Cleveland Heights, Ohio, United States

John R. Sedor,

Background

Germline and somatic genomic variation represent the bulk of ‘omics data in precision medicine research. These data, however, may fail to capture the dynamic biological processes that underlie disease development, particularly for diseases of aging such as chronic kidney disease (CKD).

Methods

To demonstrate the value of additional dynamic precision medicine data, we sequenced somatic T-cell receptor rearrangements from genomic DNA collected during a clinical encounter from 15 CKD participants. Participants were consented as part of a larger precision medicine research project at a large urban public hospital. Genomic DNA was extracted from whole blood, and T cell receptors were sequenced with six replicates per sample using Adaptive Biotechnologies’ immunoSEQ assays coupled with the Illumina NextSeq PE. All sequences were assembled using Adaptive Biotechnologies’ ANALYZER bioinformatics pipeline. Demographic and clinical data closest to the time of blood draw were extracted from the electronic health record.

Results

The average age of patients was 61.73 years, more than half (60%) were female, and the majority were African American (80%). T-cell receptor diversity was estimated using productive clonality, a measure ranging from 0 (polyclonal samples; more diversity) to 1 (oligoclonal samples; less diversity). Productive clonality in this sample ranged from 0.0151 to 0.2565 with a mean of 0.1030 (standard deviation or SD=0.0669). Average productive clonality did not statistically differ by sex: females = 0.0811 (SD=0.0533) and males = 0.1358 (SD=0.0764). We then tested for correlations between T-cell receptor diversity and biomarkers of CKD, including disease status calculated using the CKD-EPI equation. Reduced T-cell diversity was associated with increased creatinine (R²=0.0995). BUN (R²=0.0258), and eGFR (R²=0.066) but not with white blood cell count (R²=0.0004). Reduced T-cell diversity was also associated with worsening CKD status (R²=0.2362), with a higher on average productive clonality (0.0488) among stage 4 patients (n=5) compared with stage 3 (0.0330; n=8) and stage 2 patients (0.0149; n=2).

Conclusion

These data suggest an association between advanced CKD and premature aging of the adaptive immune system and highlight the potential of dynamic ‘omic data to generate novel hypotheses about disease mechanisms.