Kidney Week

Abstract: TH-PO542

Unveiling Prognostic Biomarkers in IgA Nephropathy: A Chromatin Accessibility Approach Using Peripheral Immune Cells

Session Information

• Glomerular Diseases: Omics, Biomarkers, and Tools
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Lee, Soojin, Eulji University Uijeongbu Eulji Medical Center, Uijeongbu, Gyeonggi-do, Korea (the Republic of)

Soojin Lee, MD, PhD

• Kim, Gwanghun, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea (the Republic of)

Gwanghun Kim, PhD

• Koh, Jung Hun, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)

Jung Hun Koh, MD

• Park, Sehoon, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)

Sehoon Park, MD, PhD

• Kim, Yaerim, Keimyung University School of Medicine, Daegu, Korea (the Republic of)

Yaerim Kim, MD, PhD

• Kim, Hang-Rae, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea (the Republic of)

Hang-Rae Kim, PhD, DVM

• Kim, Dong Ki, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)

Dong Ki Kim, MD, PhD

Background

IgA nephropathy (IgAN), the most prevalent primary glomerulonephritis globally, exhibits heterogeneous clinical presentation and prognosis. The disease’s heterogeneity remains enigmatic due to incomplete understanding of pathogenesis. This study employs an epigenetic approach to comprehensively profile peripheral immune cells in IgAN patients, aiming to elucidate their role in disease progression.

Methods

Peripheral blood mononuclear cells were obtained from 57 biopsy-proven IgAN patients and 20 healthy controls and were FACS sorted into B cells, CD4+ T cells, and CD8+ T cells. To explore the role of immune cells in IgAN pathogenesis, we performed Assay for Transposase-Accessible Chromatin (ATAC) Sequencing using NovaSeq 6000. Quality control and normalization process was performed consecutively to identify the differential peaks.

Results

After peak-calling, 65,234 peaks in B cells, 61,007 peaks in CD4+ T cells, and 59,162 peaks in CD8+ T cells, were considered for the differential ATAC-peak selection according to the patient groups. (Figure 1) Differential ATAC-peaks were highest in the CD8+ T cell subset compared to other immune cell populations. Gene ontology analysis showed significant functional differences in CD8+ T cells, when categorized by IgAN progression status. Interestingly, both B and CD4+ T cell subsets displayed significant chromatin accessibility differences, specifically within the ST6GALNAC5 gene locus. (Figure 2)

Conclusion

The present study offers novel insights into the role of immune cells in IgAN pathogenesis. Our findings hold promise for the development of novel, disease-specific biomarkers for improved prognosis assessment in IgAN patients.

Fig 1. The number of differential peaks.

Fig 2. The results of gene ontology analysis

Funding

• Government Support – Non-U.S.