115. Circulatory peripheral T helper (PTH) cells in PR3 ANCA associated vasculitis (PR3 AAV)
Creators: name: Seerapani Gopaluni1
name: Jayne1, David
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background</strong><strong>:</strong> Evidence from different strands supports the importance of CD4 T cells in disease pathogenesis and in the persistence or relapse of disease activity in ANCA associated vasculitis (AAV). A subset of T helper cells expressing PD1 but not CXCR5 (referred to as peripheral T helper (PTH) cells) were shown to help B cell survival and proliferation at sites of inflammation in rheumatoid arthritis and lupus. This study was aimed at understanding the relevance of these cells in PR3-ANCA positive AAV (PR3 AAV). <strong>Methods:</strong> Blood samples from 21 patients with active PR3 AAV, 51 PR3 AAV patients in remission, 20 age-matched disease controls (giant cell arteritis, SLE, IgA Vasculitis) and 37 healthy volunteers (HV) were obtained, along with paired urine samples from 28 of the PR3 AAV patients. Lymphocytes were extracted from the samples for flowcytometric and functional analyses. Kidney biopsy samples from patients with active nephritis were stained for the presence of PTH cells. <strong>Results:</strong> PR3 AAV patients, either in remission or with active disease had a higher proportion of circulatory PTH (cPTH) cells compared to HVs and disease controls. Further, the ratio between cPTH and circulatory TFH (cTFH) cells was also higher in PR3 AAV patients compared to both HVs and disease controls, suggesting a skewing of CD4 T cells towards a cPTH phenotype. The proportion of cPTH cells was higher in PR3-AAV patients with elevated inflammatory markers, CRP (p=0.034) and ESR (p=0.03). In a subset of 15 patients sampled before and 3 months after induction therapy there was a reduction in the proportion of cPTH cells (p=0.041) as well as the proportion of activated (HLA-DR+) cPTH cells (p=0.05) suggesting a correlation with disease activity. PR3 AAV patients with active renal disease had a higher number of CD4 T cells/dL in urine (p=0.023) and a higher proportion these were PTH cells (p=0.024) compared to those in remission. Immunofluorescent staining of kidney biopsy samples from PR3 AAV patients with nephritis revealed the presence of CD4 T cells expressing PD1 infiltrating the tubules of kidney tissue. <strong>Conclusions:</strong> In the current study, CD4 T cells were present in the urine of PR3-AAV nephritic patients and were reduced or disappeared as remission was achieved, and 25% of urinary CD4 T helper cells were of a PTH phenotype, expressing PD1+ but not CXCR5. As histological studies also found CD4+PD1+ cells infiltrating the tubules and interstitium of the kidney these observations are consistent with a nephritogenic role for this subset. cPTH cells were expanded in the peripheral circulation of patients with PR3-AAV irrespective of their disease status when compared to age-matched HVs and disease controls reflecting the persistence of T cell dysregulation despite apparent control. In paired samples, the frequencies of cPTH cells and activated cPTH within the CD4 compartment fell with treatment, suggesting an association with disease activity. cPTH cells were also higher in patients with increased inflammatory markers. <strong>Disclosures:</strong> The authors have no financial disclosures relevant to the submitted work. <strong>Figure 1.</strong> Immunofluorescence staining of kidney tissue from a patient with active nephritis. Top left image shows DAPI staining of a section of the tissue, top right shows AF488 CD4 staining. A white arrow is placed to show a CD4 cell infiltrating the tubule. Bottom left panel shows AF594 staining for PD1, whilst bottom right image is a merge of all three stains. Similar staining could also be seen in another three adjacent tubules (shown by smaller white triangles). CD4 T cells/dL of urine in a) PR3 AAV patients with or without renal disease b) patients with or without active renal involvement