Chapter 22: Autoimmune Disease Mechanisms

Autoimmune diseases present a complex challenge in modern medicine, with the body’s defense system mistakenly attacking its own tissues. Mass cytometry has emerged as a powerful tool to decode these intricate disease mechanisms. Let’s explore how this technology has advanced our understanding of specific autoimmune conditions and their potential treatments.

Rheumatoid Arthritis: Unveiling Novel Cell Subsets

Rheumatoid arthritis (RA) has been a prime target for mass cytometry research, leading to groundbreaking discoveries.

The landmark study by Rao et al. (2017) published in Nature, cited almost 1000 times, “Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis,” used mass cytometry to identify a novel subset of T helper cells in RA patients. This PD-1hiCXCR5- T peripheral helper (Tph) cell population was found to promote B cell responses and inflammation. This discovery has fundamentally changed our understanding of RA pathogenesis, suggesting that these Tph cells, rather than follicular helper T cells, may be the primary drivers of B cell responses in RA.

Systemic Lupus Erythematosus: Mapping Cytokine Networks

In systemic lupus erythematosus (SLE), mass cytometry has been instrumental in mapping complex cytokine networks.

A study by Arazi et al. (2019) published in Nature Immunology, titled “The immune cell landscape in kidneys of patients with lupus nephritis,” used mass cytometry to analyze tissue-resident immune cells in an autoimmune condition. The researchers employed a 35-marker mass cytometry panel to profile kidney samples from patients with lupus nephritis, a severe complication of systemic lupus erythematosus.

They identified 22 immune cell populations and discovered previously unrecognized immune cell types in the kidneys of lupus patients. This study highlighted the importance of tissue-specific immune responses in autoimmune diseases, revealing how different immune cell subsets interact within the affected organ. The findings provided new insights into the pathogenesis of lupus nephritis and demonstrated the power of mass cytometry in unraveling complex tissue-resident immune landscapes in autoimmune conditions.

A pivotal study by Nehar-Belaid et al. (2020) in Nature Immunology, “Mapping systemic lupus erythematosus heterogeneity at the single-cell level,” used flow cytometry alongside other single-cell technologies to create a comprehensive atlas of immune cell states in SLE. They identified distinct subsets of effector CD4+ T cells and activated B cells associated with disease activity, providing new targets for therapeutic intervention.

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When I dived into the world of autoimmune diseases with Esther, I realized immunology is like a vast ocean - every time you think you've seen it all, you discover a new depth. Our paper, "Proinflammatory T Helper 17 Cells Are Increased in Remission Rheumatoid Arthritis Patients and Triggered by Synergy Between Low-Dose Interleukin-7 and Interleukin-15" (Koppejan et al., 2022), was just the tip of the iceberg. Working on rheumatoid arthritis opened my eyes to the complexity of the immune system. But the real surprise? It became the perfect playground for developing Cytofast. Suddenly, I was collaborating with more people than I ever imagined possible. It was like hosting a scientific potluck where everyone brought their expertise to the table. Who knew that diving into autoimmune diseases would lead to creating a tool that brought the scientific community closer together? In the end, immunology didn't just teach me about cells - it taught me about connections, both cellular and human.

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