Circulating CD24hiCD38hi Regulatory B-Cells Influence Th17-Cell Responses in Patients with Granulomatosis with Polyangiitis

Anouk von Borstel¹, Lucas L. Lintermans², P Heeringa³, Abraham Rutgers², Coen A. Stegeman¹, Jan-Stephan F. Sanders¹ and Wayel H. Abdulahad², ¹Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands, ²Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands, ³Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands

Meeting: ACR/ARHP Annual Meeting 2018

Keywords: B cells, regulatory cells and vasculitis, T cells

Session Information

Date: Sunday, October 21, 2018

Title: B Cell Biology and Targets in Autoimmune and Inflammatory Disease Poster

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:

To investigate whether there is a direct relation between expanded proportions of Th17-effector memory (Th_EM17) cells and diminished proportions of regulatory B-cells (Bregs) in peripheral blood of granulomatosis with polyangiitis (GPA) patients.

Methods:

Frequencies of both Bregs and Th_EM17-cells were determined by FACS in blood samples from 42 GPA-patients in remission and 18 matched healthy controls (HCs). Breg frequency was defined as the percentage of CD24^hiCD38^hi cells within the CD19⁺ population. Th_EM17-cell frequency was defined as the percentage of CCR6⁺CXCR3^–CCR4⁺ cells within the CD3⁺CD4⁺CD45RO⁺CCR7^– population. In addition, CD3⁺CD4⁺ Th-cells were sorted from 9 GPA-patients and co-cultured with either total B-cells or with a Breg-depleted cell fraction. Cultured cells were stimulated with Staphylococcus Enterotoxin B (SEB) and CpG-oligodeoxynucleotides (CpG-ODN). Frequencies of Th17- (IL-17⁺) and Th1-cells (IFNg⁺) were determined at baseline and day 5 upon restimulation with PMA and Ca²⁺ ionophore.

Results:

In remission GPA-patients, the Breg frequency was lower (p<0.05), whereas the Th_EM17-cell frequency was increased (p<0.001) compared to HCs. In remission GPA-patients the circulating Breg frequency correlated negatively with circulating Th_EM17-cell frequency (r=-0.371; p=0.007). The co-culture experiments revealed a significant increase in the frequency of IL-17⁺ Th-cells in Breg-depleted samples (median:3%; range:1-7.5%) compared to undepleted samples (p=0.002; undepleted samples median:2.1%; range:0.9-6.4%), whereas a trend towards a decrease in the frequency of IFNg⁺ Th-cells in Breg-depleted cultures was observed (p=0.08; undepleted median:11.8%; range:2.8-21% vs. Breg-depleted median:12.2%; range:2.6-17.6%).

Conclusion:

Bregs modulate Th_EM17 responses in AAV-patients. Future studies should elaborate on clinical and therapeutic implications of the Breg-Th17 interaction in GPA patients.

Disclosure: A. von Borstel, None; L. L. Lintermans, None; P. Heeringa, None; A. Rutgers, None; C. A. Stegeman, None; J. S. F. Sanders, None; W. H. Abdulahad, None.

To cite this abstract in AMA style:

von Borstel A, Lintermans LL, Heeringa P, Rutgers A, Stegeman CA, Sanders JSF, Abdulahad WH. Circulating CD24hiCD38hi Regulatory B-Cells Influence Th17-Cell Responses in Patients with Granulomatosis with Polyangiitis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/circulating-cd24hicd38hi-regulatory-b-cells-influence-th17-cell-responses-in-patients-with-granulomatosis-with-polyangiitis/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/circulating-cd24hicd38hi-regulatory-b-cells-influence-th17-cell-responses-in-patients-with-granulomatosis-with-polyangiitis/