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Study identifies new subtypes of pSS, SLE based on immunological profiles

By Claire Barnard, Senior medwireNews Reporter

Immunological profiles could be used to categorize patients with primary Sjögren’s Syndrome (pSS) or systemic lupus erythematosus (SLE) into distinct subgroups irrespective of diagnosis, suggests UK research published in Arthritis & Rheumatology.

The study results “highlight the shared immunopathogenic processes underlying primary SS and SLE manifestations that are likely to be more relevant for treatment selection strategies than basing treatment selection on disease diagnosis alone”, say Coziana Ciurtin and colleagues from University College London.

The team used flow cytometry to evaluate 29 immune cell subsets in peripheral blood samples from women with pSS (n=45), SLE (n=29) or secondary SS associated with SLE (SS/SLE; n=14), all of whom were either in remission or had low disease activity.

These patients had disrupted immune cell profiles compared with 31 healthy controls matched for sex and ethnicity, but the researchers found “very few significant differences in immunologic architecture” between individuals with pSS and those with SLE, despite the two groups having different clinical presentations and diagnoses.

However, when people with pSS, SLE and SS/SLE were combined into one cohort, machine-learning methodology identified two distinct patient groups with significantly different immune cell phenotype patterns.

The team validated these findings using multiple methods – including univariate logistic regression and additional machine-learning analyses – and identified eight T-cell subsets that consistently differentiated between the two groups across all four analytical approaches: total CD4+; CD4+ CD45RA+ effector memory T (EMRA); total CD8+; CD8+ naïve; CD8+ EMRA; CD8+ EM; CD8+ responder and CD8+ CD25+ CD127– cells.

Area under the receiver operating characteristic curve analysis demonstrated that this signature of eight T-cell subsets differentiated between groups 1 and 2 with an accuracy of 99.8%.

“Thus, despite patients with primary SS and those with SLE having low or no disease activity, these patients could still be stratified using their immune cell profile”, write the researchers.

They also showed that patient stratification based on the immunological profiles has the potential to predict long-term outcomes. For instance, during 5 years of follow-up, patients in group 2 had overall higher disease activity and damage scores than those in group 1, as well as higher erythrocyte sedimentation levels, even though “disease activity was still predominantly low overall.”

Ciurtin and team caution that their results require external validation in a larger study, and that further research “is required to establish if the signatures we identified have predictive biomarker values for responses to certain therapies.”

Nevertheless, they conclude: “In addition to stratifying patients for better treatment selection, our results can offer new therapeutic options for patients with primary SS who share immune signatures with selected SLE patients, by providing access to treatments licensed for use in SLE.”

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Arthritis Rheumatol 2021; 73: 1626–1637