Deep Immunophenotyping Reveals Distinct Immune Signatures in Axial Spondyloarthritis and Psoriatic Arthritis.

Deep Immunophenotyping Unravels the Double Negative T cells and PD-1-Mediated Inflammatory Exhaustion in Ankylosing Spondylitis

A detailed functional immune map of biologic-naïve active AS is provided, offering novel mechanistic insights and identifying candidate biomarkers for precision intervention.

Integrated peripheral immune profiling reveals B-cell dysregulation and CD8 effector signatures in chronic inflammatory demyelinating polyneuropathy

Background Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated peripheral neuropathy with heterogeneous and often incomplete responses to current immunotherapies, but the underlying immune basis remains poorly defined. Although CIDP shares features of immune-mediated demyelination with multiple sclerosis (MS), the two diseases affect distinct anatomical compartments and exhibit divergent therapeutic responses, suggesting fundamentally different underlying immune programs. Here, we address this gap by defining the peripheral immune architecture of CIDP using an integrated, multi-modal approach. Methods Peripheral blood was obtained from 20 patients with CIDP and 20 age- and sex-matched healthy controls. Single-cell RNA sequencing was performed in a discovery subset and integrated with publicly available MS peripheral blood datasets to provide a cross-disease reference framework. The single-cell analysis was designed as an exploratory discovery step to identify candidate immune signatures. Transcriptomic, pathway, and ligand–receptor analyses were complemented by cytokine profiling and flow-cytometric validation in the full cohort. Results CIDP exhibited broad inflammatory activation with preferential enrichment of type I interferon and inflammasome-related programs compared with MS. Despite reduced B-cell frequencies, CIDP showed transcriptional enrichment of germinal center–associated programs, indicating a dissociation between cell number and activation state. In parallel, CD8 effector T cells demonstrated enhanced cytotoxicity and cytoskeletal remodeling programs, supported by increased expression of actin-regulatory genes and strengthened intercellular signaling interactions. In contrast, MS showed greater enrichment of integrin–talin–vinculin signaling pathways in B cells and CD4 T-cell subsets, consistent with trafficking-related immune mechanisms. Together, these findings indicate a coordinated immune axis linking B-cell dysregulation and cytotoxic CD8 T-cell activation in CIDP. Conclusions Integrated peripheral immune profiling identified candidate CIDP-associated immune signatures including dysregulated B-cell activation despite numerical reduction and a prominent cytotoxic CD8 T-cell program within a type I interferon– and inflammasome-skewed inflammatory milieu. These findings provide an exploratory framework for understanding peripheral immune dysregulation in CIDP and warrant further translational studies in larger, treatment-stratified cohorts.

Cross-disease immunological comparison reveals shared systemic immune activation across the broader spondyloarthritis spectrum.

To perform cross-disease immunological comparison across the broader spondyloarthritis (SpA) spectrum and examine their association with disease activity. We analyzed 111 patients with active broader SpA spectrum (ankylosing spondylitis, inflammatory bowel disease-associated SpA, psoriatic arthritis, pustulotic arthro-osteitis, and chronic non-bacterial osteitis) and 24 age- and sex-matched healthy controls (HC). Serum IL-17A, IL-17F, TNFα, and Oncostatin M levels were higher in the broader SpA spectrum than in HC. These cytokines levels did not differ among the broader SpA spectrum. Activated Th17, activated Th1-17, classical and intermediate monocytes were increased in the broader SpA spectrum compared with HC. Although Kruskal-Wallis test showed differences among the spectrum for activated Th17, activated Th1-17, and classical monocytes, post hoc analyses did not identify a specific disease driving these differences. Intermediate monocytes positively correlated with CRP and MMP-3 levels. Circulating immune subsets remained unchanged following DMARDs treatment despite clinical improvement. Systemic immune alterations, including activation of IL-17 axis, elevated Oncostatin M, and expansion of intermediate monocytes, are broadly shared across the broader SpA spectrum. Although global differences among the spectrum were observed for some immune cell populations, post hoc analyses did not identify disease-specific enrichment.

The Integrin Signature of Ankylosing Spondylitis: Divergent Regulation of CD29 and CD49b in HLA-B27-Positive Cohorts in Iraqi Patients

A divergent regulation of CD29 and CD49b integrins associated with HLA-B27 status in Iraqi AS patients is suggested and longitudinal validation is required to confirm their clinical utility as diagnostic or therapeutic targets.

STK17B/DRAK2 in Axial Spondyloarthritis: Expression Patterns in Blood and Tissue

Pre-biologic STK17B expression was higher among patients who were later identified as non-responders to IL-17i compared with responders, suggesting that DRAK2 upregulation contributes to axSpA-related inflammation and to treatment resistance, warranting further mechanistic investigation.

Profiling immune cell subsets in pediatric IgA vasculitis and immune thrombocytopenia: insights into disease pathogenesis and clinical correlates.