Deep Immunophenotyping of Circulating T and B Cells in Relapsing Adult-Onset Still’s Disease

Surae Rein^*
*Correspondence: Surae Rein, Department of Immunology, Moscow State University, Moscow, Russia, Email:

Introduction

Recent advances in deep immunophenotyping techniques offer a new perspective on the immunological dysregulation underlying AOSD, with a specific focus on circulating T and B cells. This article provides a comprehensive overview of the current understanding of immunophenotyping in relapsing AOSD, highlighting its potential implications for diagnosis, prognosis and targeted therapy. AOSD is characterized by dysregulated innate and adaptive immune responses, leading to systemic inflammation and tissue damage. While the exact etiology remains elusive, current evidence suggests a multifactorial interplay between genetic predisposition, environmental triggers and immunological dysregulation. Innate immune cells, including monocytes, macrophages and neutrophils, play a crucial role in the initiation and perpetuation of inflammation, producing pro-inflammatory cytokines such as Interleukin (IL)-1β, IL-6 and Tumor Necrosis Factor-Alpha (TNF-α). However, emerging evidence indicates a pivotal role for adaptive immune cells, particularly T and B lymphocytes, in the pathogenesis of AOSD, especially during relapse episodes. Adult-Onset Still’s Disease (AOSD) is a rare auto inflammatory disorder characterized by fevers, rash, arthritis and systemic inflammation. Despite its rarity, AOSD presents significant diagnostic and therapeutic challenges, particularly in cases of relapse where conventional treatments may be inadequate [1,2].

Description

Relapse episodes in AOSD are characterized by the reactivation of systemic inflammation and clinical manifestations, often refractory to conventional treatments. Deep immunophenotyping studies have provided insights into the immunological basis of relapsing AOSD, highlighting the role of T and B cell subsets in perpetuating chronic inflammation and tissue injury. T cell dysregulation is a hallmark of relapsing AOSD, with increased frequencies of activated CD4+ and CD8+ T cells observed during active disease phases. Mass cytometry enables high-dimensional profiling of immune cells by simultaneously detecting multiple markers at the single-cell level, overcoming the limitations of spectral overlap encountered in conventional flow cytometry. By applying CyTOF to peripheral blood samples from AOSD patients, researchers have delineated distinct T and B cell subsets associated with disease activity and severity, revealing novel biomarkers and potential therapeutic targets. Single-cell RNA sequencing provides transcriptomic profiles of individual cells, allowing for the characterization of gene expression patterns and cellular heterogeneity within complex immune cell populations. In AOSD, scRNA-seq has unveiled transcriptional signatures of pathogenic T and B cell subsets, elucidating key signaling pathways and molecular mechanisms driving inflammation and tissue damage [3,4].

Immunophenotyping allows for the comprehensive characterization of immune cell subsets, including their phenotype, activation status and functional properties. Traditional flow cytometry has been instrumental in identifying alterations in T and B cell populations in AOSD, such as increased frequencies of activated CD4+ T cells and plasmablasts during active disease states. However, recent advancements in deep immunophenotyping techniques, such as mass cytometry (CyTOF) and single-cell RNA sequencing (scRNA-seq), offer unprecedented insights into the heterogeneity and dynamics of immune cell populations in AOSD, particularly during relapse. Furthermore, aberrant cytokine production, such as elevated levels of IL-17 and Interferon-Gamma (IFN-γ), contributes to the perpetuation of inflammation and tissue damage in relapsing AOSD. Immunophenotyping studies have identified distinct T cell subsets, including Th17 and cytotoxic T cells, as drivers of disease pathogenesis, providing potential targets for immunomodulatory therapies. B cell abnormalities are also implicated in the pathogenesis of relapsing AOSD, with expanded populations of plasmablasts and memory B cells observed during active disease states. Dysregulated B cell activation and differentiation contribute to the production of autoantibodies and pro-inflammatory cytokines, perpetuating chronic inflammation and tissue damage. Deep immunophenotyping studies have identified specific B cell subsets, such as CD27+ memory B cells and antibody-secreting cells, as potential biomarkers of disease activity and therapeutic targets [5].

Conclusion

However, translating these immunophenotyping findings into clinically actionable biomarkers and personalized treatment strategies remains a challenge. Standardization of immunophenotyping protocols, validation of biomarkers in large patient cohorts and integration of multi-omic data are needed to enhance the diagnostic accuracy and prognostic value of immunophenotyping assays in clinical practice. Deep immunophenotyping of circulating T and B cells offers valuable insights into the pathogenesis of relapsing AOSD, unraveling the complex interplay between innate and adaptive immune responses. By characterizing the heterogeneity and dynamics of immune cell populations, these techniques provide opportunities for identifying novel biomarkers and therapeutic targets in AOSD. Similarly, therapies targeting B cell activation and differentiation, such as rituximab, have demonstrated promise in reducing autoantibody production and attenuating systemic inflammation in AOSD. Moreover, deep immunophenotyping studies have shed light on the cytokine milieu associated with relapsing AOSD, with elevated levels of pro-inflammatory cytokines such as Interleukin-6 (IL-6) and Interferon-Gamma (IFN-γ) implicated in driving immune dysregulation and disease flares. This cytokine imbalance underscores the importance of targeted therapies aimed at modulating specific cytokine signaling pathways to mitigate inflammation and prevent disease relapses. Importantly, deep immunophenotyping has identified potential therapeutic targets for relapsing AOSD. Agents targeting IL-6, such as tocilizumab, have shown efficacy in controlling disease activity and improving patient outcomes. Future research efforts aimed at integrating immunophenotypic data with clinical parameters hold promise for improving the diagnosis, prognosis and management of relapsing AOSD, ultimately enhancing patient outcomes and quality of life.

Acknowledgement

None.

Conflict of Interest

There are no conflicts of interest by author.

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