Lymphocyte subset phenotyping for the prediction of progression to inflammatory arthritis in anti-citrullinated-peptide antibody-positive at-risk individuals

Anioke,Innocent; Duquenne,Laurence; Parmar,Rekha; Mankia,Kulveer; Shuweihdi,Farag; Emery,Paul; Ponchel,Frederique

Lymphocyte subset phenotyping for the prediction of progression to inflammatory arthritis in anti-citrullinated-peptide antibody-positive at-risk individuals

All Authors

Anioke,Innocent

Duquenne,Laurence

Parmar,Rekha

Mankia,Kulveer

Shuweihdi,Farag

Emery,Paul

Ponchel,Frederique

LTHT Author

Duquenne, Laurence
Mankia, Kulveer
Emery, Paul

LTHT Department

NIHR Leeds Biomedical Research Centre
Rheumatology

Publication Date

2024

Item Type

Article

Abstract

Objectives Inflammatory arthritis (IA) is considered the last stage of a disease continuum, where features of systemic autoimmunity can appear years before clinical synovitis. Time to progression to IA varies considerably between at-risk individuals, therefore the identification of biomarkers predictive of progression is of major importance. We previously reported on the value of three CD4+T cell subsets as biomarkers of progression. Here, we aim to establish the value of 18 lymphocyte subsets (LS) for predicting progression to IA. Methods Participants were recruited based on a new musculoskeletal complaint and being positive for anti-citrullinated-peptide antibody. Progression (over 10?years) was defined as the development of clinical synovitis. LS analysis was performed for lymphocyte lineages, naive/memory subsets, inflammation-related cells (IRC) and regulatory cells (Treg/B-reg). Modelling used logistic/Cox regressions. Results Of 210 patients included, 93 (44%) progressed to IA, 41/93 (44%) within 12?months (rapid progressors). A total of 5/18 LS were associated with progression Treg/CD4-na飗e/IRC (adjusted P ?<?0.0001), CD8 (P ?=?0.021), B-reg (P ?=?0.015)] and three trends (NK-cells/memory-B-cells/plasmablasts). Unsupervised hierarchical clustering using these eight subsets segregated three clusters of patients, one cluster being enriched 63/109(58%)] and one poor 10/45(22%)] in progressors. Combining all clinical and LS variables, forward logistic regression predicted progression with accuracy?=?85.7% and AUC?=?0.911, selecting smoking/rheumatoid-factor/HLA-shared-epitope/tender-joint-count-78 and Treg/CD4-naive/CD8/NK-cells/B-reg/plasmablasts. To predict rapid progression, a Cox regression was performed resulting in a model combining smoking/rheumatoid factor and IRC/CD4-naive/Treg/NK-cells/CD8+T cells (AUC?=?0.794). Conclusion Overall, progression was predicted by specific LS, suggesting potential triggers for events leading to the development of IA, while rapid progression was associated with a different set of subsets.