Session Type: Abstract Submissions (ACR)
Background/Purpose: Persistent expansion of circulating CD4+ effector memory T cells (TEM) in patients with Granulomatosis with polyangiits (GPA) suggest their fundamental role in disease pathogenesis. The functional phenotype of these CD4+ TEM cells in GPA-patients is not known. Recent studies have shown that 4 distinct functional subsets of CD4+ TEM cell can be identified based on the expression pattern of the chemokine receptors CXCR3, CRTh2, CCR4, and CCR6. The current study aimed to identify functionally reported different phenotypes within the expanded CD4+ TEM cell population in peripheral blood of GPA-patients.
Methods: Peripheral blood of 43 GPA-patients in remission and 16 healthy controls (HCs) was stained immediately after blood withdrawal with fluorochrome-conjugated antibodies for cell surface markers (CD3, CD4, CD45RO) and chemokine receptors (CCR4, CCR6, CCR7, CRTh2, CXCR3) followed by flow cytometry analysis. Positively and negatively stained populations were calculated by dot plot analysis, determined by the appropriate isotype controls. Expression patterns of chemokine receptors CXCR3+CRTh2–CCR4–CCR6–, CXCR3–CRTh2+CCR4+CCR6–, CXCR3–CRTh2–CCR4+CCR6+, and CXCR3+CRTh2–CCR4–CCR6+ were used to distinguish Th1, Th2, Th17, and Th1/17 cells, respectively.
Results: The percentage of CD4+ TEM (CD3+CD4+CD45RO+CCR7–) cells was significantly increased in GPA-patients in remission compared to HCs (median 41,93% vs 31,52%). Chemokine receptor co-expression analysis within the CD4+ TEM cell population demonstrated similar percentages of Th1 and Th2 cells between GPA-patients and HCs. Interestingly, the analysis revealed a significant decrease in the frequency of Th1/17 cells (median 9,28% vs 16,53%) with a concomitant significant increase in the Th17 cells (median 21,14% vs 16,93%) in GPA-patients compared to HCs. However, differences between these CD4+ TEM cell subsets were not related to generalized or localized disease, ANCA positivity at the time of inclusion, nor to immunosuppressive treatment regimens.
Conclusion: Based on chemokine receptor co-expression analysis we demonstrate an aberrant distribution in the CD4+ TEM cell compartment in GPA-patients. The identification of different phenotypes within the expanded CD4+ TEM cell population revealed a distinction between Th1/17 cells and Th17 cells. Interestingly, it has been described that the functional and molecular signature of Th1/17 cells is associated with a strong pathogenicity of this subset and may be important in mediating chronic inflammation. Analyzing the migration capacity of Th1/17 cells might reveal their distinct tissue homing characteristic to inflamed lesions in GPA-patients.
L. L. Lintermans,
C. A. Stegeman,
W. H. Abdulahad,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/decreased-cxcr3ccr4-ccr6-cd4-effector-memory-t-cells-in-patients-with-granulomatosis-with-polyangiitis/