ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: L24

A Progressive Increase in T Follicular Helper Cells Marks the Transition from Benign to Symptomatic Autoimmunity

Sina Rusta-Sallehy1, Babak Noamani2, Dennisse Bonilla3, Nan-Hua Chang4, Larissa Lisnevskaia5, Sindhu R. Johnson6, Earl Silverman7, Arthur A. M. Bookman8, Joan E. Wither9 and Carolina Landolt-Marticorena3, 1Medicine, University of Toronto, Toronto, ON, Canada, 2Genetics and developmental biology, Toronto Western Research Institute, Toronto, ON, Canada, 3Rheumatology, Toronto Western Hospital, Toronto, ON, Canada, 4Genetics and Development, Toronto Western Research Institute, Toronto Western Hospital, Toronto, ON, Canada, 5Rheumatology, Lakeridge Health Center, Toronto, ON, Canada, 6Medicine, Toronto Scleroderma Program, Toronto Western Hospital, Toronto General Hospital, Mount Sinai Hospital, and University of Toronto, Toronto, ON, Canada, 7Division of Rheumatology, Hosp for Sick Children, Toronto, ON, Canada, 8Division of Rheumatology, Toronto Western Hospital (UHN), Toronto, ON, Canada, 9Toronto Western Research Institute, Toronto Western Hospital, Toronto, ON, Canada

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: ACR Late-breaking Abstract Poster Presentations

Session Type: Late-Breaking Abstracts

Background/Purpose: The systemic autoimmune rheumatic diseases (SARD; Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), Sjogren’s Disease (SjD), Systemic Sclerosis (SSc)) are proposed to have a prolonged period of pre-clinical autoimmunity culminating in clinical disease.  Evidence from disease-specific studies (e.g., SLE and RA) suggests that this pre-clinical phase is marked by the accumulation of pathogenic auto-antibodies.  However, the cellular derangements that promote this auto-antibody (auto-Ab) production are unknown.  T follicular helper (TFH) cells drive plasma cell differentiation and immunoglobulin production and are implicated in the development of autoimmunity.  TFH cell expansion has been noted in patients with established SLE and RA but has not been defined in patients with pre-clinical SARD autoimmunity.  Here we examined the relationship between TFH cells and auto-Ab profile in ANA positive individuals prior to the development of SARD.

Methods: Patients (n = 63) who were ANA+ (titer ≥ 1:160) were recruited from a tertiary care rheumatology center.  Healthy controls (n = 27) with no history of autoimmunity, were also recruited.  Patients were stratified into clinical groups; (1) no defining SARD symptoms (n = 19), (2) undifferentiated connective tissue disease (UCTD, n = 12); one or more SARD defining symptom, (3) SARD (n = 32); fulfilling ACR criteria for a diagnosis of SLE, SjD, RA or SSc.  All patients were steroid and DMARD naive with a small proportion on HCQ (n = 6). PBMCs were isolated over a Ficoll gradient, stained with combinations of fluorescently labeled antibodies and analyzed by flow cytometry.  The extractable nuclear antigen auto-Ab profile (anti-Ro, -La, -Sm, -RNP, -Scl-70, -centromere) was determined. The Mann-Whitney non-parametric test was used to compare patient groups with p < 0.05 indicating a statistically significant difference.

Results: The proportion of TFH (CD4+, CXCR5high, PD-1high) cells was significantly elevated (p = 0.04) in patients vs controls.  UCTD patients had a significant expansion in TFH cells when compared to asymptomatic ANA+ individuals (p = 0.009).  SARD patients (vs UCTD) showed a non-significant trend to increased proportions of TFH. Patients (n = 45) with higher ANA titers (≥ 1:640) had a statistically significant increase (p = 0.01) in TFH when compared to individuals (n = 9) with lower ANA levels (1:160).  Linear regression analysis showed a positive correlation (p < 0.0001) between the proportion of TFH and the number of auto-Abs within the patient population.

Conclusion: In ANA+ individuals, expansion of TFH cells was associated with the accrual of auto-Abs and the development of clinical symptoms, suggesting that dysregulation of this cellular compartment contributes to the progression towards clinical significant autoimmunity.   This identifies TFH cells as potential targets for therapeutic intervention to prevent the development of overt clinical disease.

Disclosure:

S. Rusta-Sallehy,
None;

B. Noamani,
None;

D. Bonilla,
None;

N. H. Chang,
None;

L. Lisnevskaia,
None;

S. R. Johnson,
None;

E. Silverman,
None;

A. A. M. Bookman,
None;

J. E. Wither,
None;

C. Landolt-Marticorena,
None.

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