Rheumatoid arthritis (RA), a common chronic autoimmune disease, is characterized by persistent synovial and systemic inflammation, potentially leading to irreversible joint damage.
A hallmark of RA is the presence of autoantibodies, such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). ACPA are highly disease-specific, and their presence is associated with more severe disease and poor prognosis compared to ACPA-negative patients (ACPA−). The pathogenesis of RA is incompletely understood, apart from a role for B cells, given the efficacy of B cell-depleting therapies. Several studies investigating RA on the immune cell level report on decreased frequencies of regulatory T cells in RA patients.ĭespite great efforts by the field, data on the immune cell composition truly associated with RA is limited. Likewise, CCR6 expression was reported to be upregulated in CD4 +CD45RO + T helper cells in ACPA-positive (ACPA+) disease, as was an increase in the frequency of CD4, CD8 double-positive T cells and the ratio of M1/M2 monocytes in peripheral blood. In contrast, a signature CD4 + T cells compatible with IL-6-mediated STAT3 signalling was observed mostly in ACPA− disease during the early clinical phase. These studies generally focused on a specific cell type or immune cell subset present in the immune system providing limited information on the overall cellular composition of the major immune lineages in RA and/or RA endotypes. Moreover, few findings have been replicated which could be due to treatment effects or differences in disease duration. The analyses of the immune cell composition by high-dimensional single-cell platforms such as mass cytometry (MC), also known as cytometry by time of flight, offer new possibilities to gain additional insights into the cellular composition within rheumatic diseases. MC is an antibody-based technique utilizing heavy metal isotope-conjugated probes.
Until now, MC has been used only to a limited extent to investigate rheumatic diseases.
Nonetheless, the first studies using MC have revealed novel insights as suggesting, for example, that that PD-1 hiCXCR5 −CD4 + T cells (Tph cells) are expanded in joints and blood of seropositive RA. Other studies using MC specifically reported differences in T and B cell, monocytes and neutrophils in RA as compared to controls but not comparing ACPA-positive and ACPA-negative disease.