[ACR22] Basic Research

Author: Silvia Piantoni

Izuka et al (0586) proposed a new approach of classification of the systemic immune-mediated diseases based on the associated immune cells, detected by flow cytometry. They have identified 4 clusters that included 11 immune cells. Each cluster showed high proportions of CD8⁺ T in cluster 1, central memory CD8⁺ T, Tfh, non-classical monocytes in cluster 2, unswitched memory B, switched memory B, myeloid DC, and CD141⁺ myeloid DC in cluster 3, and CD4⁺ T, naïve CD4⁺ T, and classical monocytes in cluster 4. Cluster 1,2, and 4 were dominant in SLE, SSc, and IIM, respectively. Cluster 3 contained miscellaneous diseases.

Focused on RA, another impressive approach of classification was showed by Liao et al (0600). They determined the synovial cellular phenotype starting from biopsies of inflamed joints of 105 subjects looking for clinical correlations. The 6 cell type abundance  identified phenotypes, named by their dominant cell type were: (1) endothelial, fibroblast, and myeloid cells (EFM), (2) fibroblasts (F), (3) myeloid, (4) T- and B-cells (TB), (5) T cells and fibroblasts (TF), (6) T and myeloid cells (TM). Interestingly, Anti-CCP and RF positivity correlated with low % myeloid cells, while RF+ was correlated with high % T-cells. Higher DAS28-CRP was correlated with higher % T cells in the synovium while the TF cluster had the highest HAQ and patient global scores.

Floudas et al (0500) focused the research on the possibility to distinguish RA and PsA through the implementation of single cell transcriptomic analysis of sorted synovial cells. They identified RA-specific synovial T cell-derived TGF-b and macrophage IL-1b synergy in driving the transcriptional profile of invasive synovial-fibroblasts, expanded in RA compared to PsA synovial tissue. They suggested that disrupting specific immune and stromal cell interactions offers novel opportunities for targeted therapeutic intervention in RA and PsA.

Ida Celia et al (0655) analyzed 91 SLE renal biopsies to characterize fibrous crescents that are considered inactive lesions that follow crescentic glomerulonephritis. Surprisingly, they displayed an inflammatory signature (CD73, MMP9, MIP1b, and IL-8) that may indicate ongoing potentially treatable inflammation.

Scherlinger et al (2266) suggested the role of the platelet-neutrophil interaction in SLE pathogenesis. Their experiments showed that in SLE patients, circulating neutrophils expressed significantly higher levels of the P-selectin ligand CD15s compared to other immune subsets (p < 0.001), predicting platelet/neutrophil interactions.

Lindblom J et al (2223) showed a set of enriched pathways of potential interest for future drug investigation in CNS lupus, including BTK and C3aR inhibition, and B cell depletion through an integrated multilevel omics.

Troldborg et al (1697) demonstrated a general complement activation (classical pathway) in active SLE measuring circulating C1s/C1inh and MASP1/C1inh complexes (related to classical or lectin pathway, respectively). C1s/C1inh concentrations were significantly increased in active SLE patients (SLEDAI >6) compared to SLE patients with low disease activity (SLEDAI < 6, p< 0.01) and C1s/C1inh concentrations correlated with SLEDAI score (r=0.285, p< 0.01). In active lupus nephritis (LN), plasma concentrations of MASP1/C1inh were significantly elevated compared to non-active LN (p=0.02).

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