Dataset Information

Circulating mature granzyme B+ T cells distinguish Crohn's disease-associated axial spondyloarthritis from axial spondyloarthritis and Crohn's disease.

ABSTRACT:

Background

Axial spondyloarthritis (axSpA) has strong connections with intestinal inflammation as occurs in Crohn's disease (CD). However, the immunologic mechanisms that distinguish axSpA, CD, and those with features of both diseases (CD-axSpA) are unknown. This study aimed to address this question by initial unbiased single cell RNA-sequencing (scRNAseq) on a pilot cohort followed by validating findings using flow cytometry and ELISA in a larger cohort.

Methods

Two individuals each with CD, axSpA, CD-axSpA, and healthy controls (HC) were recruited for a pilot discovery scRNAseq cohort, and the validation cohort consisted of 18 axSpA, 24 CD, 13 CD-axSpA, and 17 HC that was evaluated by flow cytometry on PBMCs and ELISAs for plasma cytokines.

Results

Uniquely, PBMCs from subjects with CD-axSpA demonstrated a significant increase in granzyme B+ T cells of both CD4+ and CD8+ lineages by both scRNAseq and flow cytometry. T cell maturation was also greater in those with CD-axSpA, particularly the CD4+ granzyme B+ population. Pathway analysis suggested increased interferon response genes in all immune cell populations within CD-axSpA. Although IFN-γ was elevated in the plasma of a subset of subjects with CD-axSpA, IL-6 was also significantly elevated.

Conclusions

Our findings support the presence of a chronic interferonopathy in subjects with CD-axSpA characterized by interferon signaling by pathway analysis and an expansion of mature, cytotoxic T cells. These data indicate fundamental immunological differences between CD-axSpA and both of the putative "parent" conditions, suggesting that it is a distinct disease with unique natural history and treatment needs.

SUBMITTER: Lefferts AR

PROVIDER: S-EPMC8140495 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:AimsFirst, to compare clinical features and biological disease modifying anti-rheumatic drugs (bDMARDs) response in patients with axial spondyloarthritis (axSpA) and axial psoriatic arthritis (axPsA). Second, to identify possible predictors of treatment response in both entities.MethodsOne-year follow-up, observational, single-center study including all patients with axSpA or axPsA who started bDMARDs therapy. Clinical features were collected at baseline while disease activity was measured at baseline, 6 and 12 months by the Ankylosing Spondylitis Disease Activity Score and the Physician Global Assessment. The frequency of patients achieving inactive disease (ID), low disease activity (LDA), high or very high disease activity and clinical improvement were compared between axSpA and axPsA. Baseline predictor factors for achieving treatment response were identified through regression models, using odds ratio (OR) as an estimate.ResultsIn total, 352 patients were included: 287 (81.5%) axSpA and 65 (18.5%) axPsA. No significant differences at baseline were observed between the two diseases for most of the characteristics. While HLA-B27 positivity was associated with axSpA (OR = 5.4; p < 0.001), peripheral manifestations were associated with axPsA (OR = 4.7; p < 0.001). The frequency of patients with axSpA and axPsA achieving ID/LDA after 6 and 12 months of bDMARDs was comparable: 53% versus 58%, p = 0.5; and 58% versus 60%, p = 0.9, respectively. Both diseases also presented similar clinical improvement. In axSpA and axPsA, male gender seemed to be associated with achieving LDA [OR at 12 months visit = 2.8 (p < 0.01) and 2.7 (p = 0.09)].ConclusionIn clinical practice, patients with axSpA and axPsA present numerous similarities, including comparable medium-term clinical response to bDMARDs. Male gender could be a predictor of treatment response in both diseases.Keyword: axial spondyloarthritis, psoriatic arthritis, axial involvement, clinical characteristics.