Journal of Translational Autoimmunity · Published 2026-08-01 · DOI 10.1016/j.jtauto.2026.100390
Anne-Lise Strandmoe, Carlo G. Bonasia, Nanthicha Inrueangsri, Wayel H. Abdulahad, Inge M. Strating, Kevin P. Mennega, Theo Bijma, Gilles F.H. Diercks, Jeroen Bremer, Jon D. Laman, Barbara Horváth, Peter Heeringa
Pemphigus vulgaris (PV) is a severe autoimmune blistering disease characterized by pathogenic autoantibodies primarily targeting desmoglein-3. B-cell depletion by rituximab (anti-CD20) is an effective first-line treatment for PV; however, relapses are frequently observed. Evidence suggests that PV is associated with immune dysregulation beyond the B-cell compartment. So far, existing studies have largely focused on selected immune components or populations, or specific clinical states such as active disease, remission, or immediate post-rituximab, leaving it unclear how prior rituximab treatment shapes the overall circulating immune landscape during active PV, including relapse.In this study, we performed high-dimensional immune profiling to characterize circulating immune-cell composition and cytokine/chemokine signatures using a 40-colour spectral flow cytometry panel and a 46-plex Luminex assay, respectively. We compared active PV patients with healthy controls and performed a subgroup analysis of rituximab-naive versus rituximab-experienced relapsed PV patients.High-dimensional immune profiling showed that active PV is associated with a redistribution of circulating immune cells, with increased monocytes and decreased lymphocytes and plasmacytoid dendritic cells, together with reduced frequencies of double-negative (CD4−CD8−) T cells and T follicular helper cells compared with healthy controls. When comparing rituximab-naive with rituximab-experienced PV patients, in rituximab-experienced patients, the cellular composition changes were confined to the B-cell compartment, showing a shift toward a naive-dominant B-cell subset distribution. In parallel, PV was characterized by elevated serum concentrations of CD40L, CCL11/eotaxin, G-CSF, IL-1RA, IL-7, CCL20/MIP-3α, PD-L1/B7-H1/CD274, PDGF-AB/BB, and CCL5/RANTES, while no differences were identified between rituximab-naive patients and rituximab-experienced relapsed PV patients. Correlation analysis revealed that prednisone dosage may increase the frequency of mature B cells, and levels of CCL11/eotaxin, and IL-7, while decreasing the frequency of plasmacytoid dendritic cells and T follicular helper cells.Together, these findings reveal a systemic immune signature of active PV involving changes in circulating monocyte, T-cell, and soluble immune compartments, whereas prior rituximab exposure in relapsed patients is associated with sustained remodelling confined to B-cell subset composition, without long-term restructuring of non–B-cell immune lineages.
Abstract from DOAJ. Public domain (CC0 1.0).
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Strandmoe, A., Bonasia, C., Inrueangsri, N., et al. (2026). Rituximab remodels the circulating immune landscape in pemphigus vulgaris revealed by high-dimensional immune profiling. Journal of Translational Autoimmunity. https://doi.org/10.1016/j.jtauto.2026.100390