Managing Symptoms of Systemic Sclerosis for the Allergist-Immunologist.

PURPOSE OF REVIEW: Systemic sclerosis (SSc) is a chronic, multisystem, autoimmune disease characterized by fibrosis, vasculopathy and immune system dysregulation. We provide a comprehensive review of features of systemic sclerosis that can potentially present to the allergist. RECENT FINDINGS: A thorough understanding of the management options is crucial for clinicians involved in the care of patients with SSc to optimize clinical outcomes. Management of systemic sclerosis has drastically changed in the last decade and continues to evolve. This review provides an overview of management strategies for the various symptoms including skin, upper and lower airway, gastrointestinal and vascular manifestations. Institution of treatment early in the disease, including referral to rheumatology or specialized scleroderma centers, can help to both prevent and manage disease complications, and improve patient quality-of-life. While the landscape of systemic sclerosis management has evolved, we continue to recognize that there is still a need for better biomarkers and targeted therapies.

A PD-1highCD4+ T Cell Population With a Cytotoxic Phenotype is Associated With Interstitial Lung Disease in Systemic Sclerosis.

OBJECTIVE: T cells contribute to tissue injury in systemic sclerosis (SSc), yet the specific T cell subsets expanded in patients with SSc remain incompletely defined. Here we evaluated specific phenotypes and functions of peripheral helper T (Tph) and follicular helper T (Tfh) cells, which have been implicated in autoantibody production, and assessed their associations with clinical features in a well-characterized cohort of patients with SSc. METHODS: Mass cytometry of T cells from peripheral blood mononuclear cells of patients with SSc and controls were evaluated using t-distributed stochastic neighbor embedding visualization, biaxial gating, and marker expression levels. Findings were validated with flow cytometry and in vitro assays. RESULTS: The frequencies of PD-1highCXCR5+ Tfh cells and PD-1highCXCR5- Tph cells were similar in patients with SSc and controls. t-distributed stochastic neighbor embedding visualization (tSNE) revealed distinct populations within the PD-1highCXCR5- cells distinguished by expression of HLA-DR and inducible costimulator (ICOS). Among PD-1highCXCR5- cells, only the HLA-DR+ICOS- cell population was expanded in patients with SSc. Cytometric and RNA sequencing analyses indicated that these cells expressed cytotoxic rather than B cell helper features. HLA-DR+ICOS- PD-1highCXCR5- cells were less potent in inducing B cell plasmablast differentiation and antibody production than comparator T helper cell populations. HLA-DR+ICOS-PD-1highCXCR5- cells were significantly associated with the presence and severity of interstitial lung disease among patients with SSc. CONCLUSION: Among PD-1highCXCR5- T cells, a subset of HLA-DR+ICOS- cells with cytotoxic features is specifically expanded in patients with SSc and is significantly associated with interstitial lung disease severity. This potential cytotoxicity appearing in the CD4 T cell population can be evaluated as a prognostic disease biomarker in patients with SSc.

Patterns of T-Cell Phenotypes in Rheumatic Diseases From Single-Cell Studies of Tissue.

High-dimensional analyses of tissue samples from patients with rheumatic diseases are providing increasingly detailed descriptions of the immune cell populations that infiltrate tissues in different rheumatic diseases. Here we review key observations emerging from high-dimensional analyses of T cells within tissues in different rheumatic diseases, highlighting common themes across diseases as well as distinguishing features. Single-cell RNA sequencing analyses capture several dimensions of T-cell states, yet surprisingly, these analyses generally have not demonstrated distinct clusters of paradigmatic T-cell effector subsets, such as T helper (Th) 1, Th2, and Th17 cells. Rather, global transcriptomics robustly identify both proliferating T cells and regulatory T cells and have also helped to reveal new effector subsets in inflamed tissues, including T peripheral helper cells and granzyme K+ T cells. Further characterization of the T-cell populations that accumulate within target tissues should enable more precise targeting of biologic therapies and accelerate development of more specific biomarkers to track activity of relevant immune pathways in patients with rheumatic diseases.