Study in Focus 1

CD8+ tissue-resident memory T cells are expanded in primary Sjögren’s disease and can be therapeutically targeted by CD103 blockade 

Primary Sjögren’s syndrome (pSS) is characterised by autoimmune epithelitis. Tissue-resident memory T cells (Trm) are a population of non- recirculating lymphocytes, primarily located in epithelial barrier tissues and the markers associated with Trm cells are CD69 and integrin CD103.  The authors aimed to elucidate the phenotype and function of Trm in pSS and to test CD103 as a therapeutic target in an SS model.

The study involved bulk RNA sequencing of salivary gland tissue of pSS patients from four different cohorts and compared it with patients who had SICCA but did not meet the criteria for pSS (nSS). The pSS salivary gland expressed a core of Trm-associated genes, more evident in the presence of ectopic lymphoid structures (ELS) when compared to nSS. With the help of IHC and confocal microscopy, the authors demonstrated that the CD103+CD8+ Trm localised within the inflammatory cells in salivary glands of pSS patients.  CD8+CD103+CD69+ cells were significantly expanded in pSS salivary gland compared with nSS. By single cell transcriptomic, the group identified CD8+ Trm and CD4+ activated T cell populations in Sjogren’s salivary glands. Authors showed that Trm cells are expanded in salivary glands of experimental Sjogren’s syndrome (ESS) mice and salivary cannulation with anti-CD103 neutralising antibodies blocked ESS.

This study highlights the key role of CD103+CD8+Trm in the induction and perpetuation of the inflammatory process in the SG of pSS patients and CD103 blockade as a novel therapeutic target in pSS.

Study in Focus 2

Altered serum metabolome as an indicator of paraneoplasia or concomitant cancer in patients with rheumatic disease

Both Rheumatic musculoskeletal diseases (RMD) and cancer are associated with a dysregulated systemic immune response. The authors investigated whether an altered serum metabolome profile could be a potential biomarker of cancer in patients with RMD.

Rheumatoid arthritis, SpA and SLE with a concomitant malignancy and their respective control groups (ie, RA/SLE/SpA without malignancy) was studied. NMR spectroscopic analysis of serum lipids and metabolites of the main cohort was done. The study found a significant difference in the metabolite concentrations and lipid ratios between RA patients with and without invasive malignancy. The concentrations of acetate, creatine, formate, glycine and the L1/L6 ratio were used as predictors in a diagnostic model. A blinded validation cohort of seven new RA patients with a history of invasive malignancy and nine new patients without cancer was classified correctly. The model could diagnose all patients with paraneoplasia (100%) but only 50% of patients with non-invasive or in situ precancerous lesions and non-melanoma skin cancers were correctly classified.

This study provides metabolomics as an active surveillance tool in RA and SpA patients with a high risk of developing cancer. 

References

1. Mauro D, Lin X, Pontarini E, et al CD8+ tissue-resident memory T cells are expanded in primary Sjögren’s disease and can be therapeutically targeted by CD103 blockade Annals of the Rheumatic Diseases 2024;83:1345-1357.

2. Gente K, Feisst M, Marx D, et al Altered serum metabolome as an indicator of paraneoplasia or concomitant cancer in patients with rheumatic disease Annals of the Rheumatic Diseases 2024;83:974-983.