Kidney Week

Abstract: FR-PO827

Patients with ANCA-Associated Vasculitis (AAV) Display Major Phenotypic Signs of T-Cell Dysfunction

Session Information

• Glomerular Diseases: Immunology, Inflammation - I
  November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1202 Glomerular Diseases: Immunology and Inflammation

Authors

• Manrique, Joaquin, Complejo Hospital de Navarra, Pamplona, Spain

Joaquin Manrique,

• Hartzell, Susan, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Susan Hartzell,

• Chan, Emilie, Mount Sinai Hospital, New York, New York, United States

Emilie Chan,

• Tassiulas, Ioannis, Mount Sinai Hospital, New York, New York, United States

Ioannis Tassiulas,

• Angeletti, Andrea, Sant'Orsola-Malpighi Hospital, Bologna, Italy

Andrea Angeletti,

• Cantarelli, Chiara, Università di Parma, Parma, Italy

Chiara Cantarelli,

• Guglielmo, Chiara, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Chiara Guglielmo,

• Andrighetto, Sofia, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Sofia Andrighetto,

• Anderson, Lisa, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Lisa Anderson,

• Cravedi, Paolo, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Paolo Cravedi,

Background

In chronic infection and tumors, persistent T cell stimulation results in functional T cell exhaustion and anergy but limited data are available on the association between chronic inflammation in AAV and T cell dysfunction.

Methods

We performed a comprehensive flow-cytometric analyses of major T cell markers of T cells dysfunction, including exhaustion (KLRG1⁺PD1⁺CD57^-), and anergy (KLRG1⁺PD1^-CD57⁺) in 20 patients with AAV with renal involvement (at clinical onset, before immunosuppressive therapy initiation) and 12 healthy controls (HC). We also measured CD4⁺CD25⁺CD127^low regulatory T cells (Treg) and intracellular IFN-g, IL-4, and IL-17 production in the same study groups.

Results

We found a remarkable and statistically significant increase in CD4⁺ and C8⁺ T cells with exhausted and anergic phenotype in AAV patients compared to HC (Fig. 1A-D). AAV patients also displayed significantly higher levels of circulating Treg (Fig. 1E). Despite Treg increase, we did not record a significant difference in intracellular cytokine production.

Conclusion

Patients with AAV display a unique immune phenotype characterized by extensive T cell dysfunction, associated with increased Treg, suggesting the existence of chronic inflammation before clinical onset of the disease.

Fig. 1. Percentages of CD4⁺ (A-B) and CD8⁺ T (C-D) cells with exhausted or anergic phenotype and regulatory T cells (Treg) (E) according to disease group and in healty controls (HC). *P〈0.05.