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Immunosuppressive treatment in diffuse cutaneous systemic sclerosis is associated with an improved composite response index (CRISS).

ABSTRACT: BACKGROUND:Outcomes of therapeutic studies in diffuse cutaneous systemic sclerosis (dcSSc) have mainly been measured for specific organs, particularly the skin and lungs. A new composite response index in dcSSc (CRISS) has been developed for clinical trials. The goal of this study was to determine whether, in an observational dcSSc cohort, immunosuppression was associated with global disease improvement measured with the CRISS. METHODS:We conducted a retrospective cohort study in a multi-centered SSc registry comparing 47 patients newly exposed to immunosuppression for ??1?year to 254 unexposed patients. Inverse probability of treatment weighting (IPTW) was performed to create comparable exposed and unexposed groups by balancing for age, sex, disease duration, modified Rodnan skin score (mRSS), forced vital capacity, patient and physician global assessments, and Health Assessment Questionnaire score. A CRISS score ??0.6 at 1?year was defined as improvement. RESULTS:Exposed patients had shorter disease duration (5.5 versus 11.7?years, p?

SUBMITTER: Zheng B

PROVIDER: S-EPMC7275378 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Immunosuppressive treatment in diffuse cutaneous systemic sclerosis is associated with an improved composite response index (CRISS).

Zheng Boyang B Hudson Marie M Wang Mianbo M Baron Murray M

Arthritis research & therapy 20200605 1

<h4>Background</h4>Outcomes of therapeutic studies in diffuse cutaneous systemic sclerosis (dcSSc) have mainly been measured for specific organs, particularly the skin and lungs. A new composite response index in dcSSc (CRISS) has been developed for clinical trials. The goal of this study was to determine whether, in an observational dcSSc cohort, immunosuppression was associated with global disease improvement measured with the CRISS.<h4>Methods</h4>We conducted a retrospective cohort study in ...[more]

PMID: 32503616

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Project description:BackgroundAbnormalities in lymphocyte surface markers and functions have been described in systemic sclerosis (SSc), but conflicting results abound, and these studies often examined patients with heterogeneous disease duration, severity, clinical phenotype, and concurrent immunosuppressive agents. We studied a clinically homogeneous group of early diffuse cutaneous SSc patients not exposed to immunosuppressive drugs who were enrolled in a clinical trial and compared their immune parameters to healthy control subjects.MethodsLymphocyte subsets were enumerated by multi-parameter flow cytometry of peripheral blood mononuclear cells at baseline visit. Production of the cytokines IL-4 and IL-17 was measured by intracellular flow cytometry following T cell activation.ResultsSSc patients had increased percentages of CD4+ T cells but lower percentages of CD8+ T cells versus controls. The CD28-negative population was expanded in SSc, in the CD4 subset. Striking expansion of CD319+ T cells was noted among the CD4+ cells, in which they were barely detectable in healthy subjects. Frequencies of IL-4 producing cells did not differ between SSc and controls, but expansion of IL-17 producing cells was observed in SSc. A higher proportion of CD319+ cells produced cytokines, compared to other CD4+ cells. Numbers of activated T cells, regulatory T cells, and B cells were similar in SSc and control groups. Circulating follicular helper but not peripheral helper T cells were slightly expanded in SSc.ConclusionIn this carefully selected group of early diffuse cutaneous SSc patients, analysis of immune cell parameters has identified abnormalities that likely reflect disease pathogenesis and that are candidate biomarkers for sub-classification and targeted treatment. The CD4+CD319+ (SLAM-F7+) cells are cytotoxic and oligoclonal, were recently shown to be a dominant T cell population in perivascular lymphocytic infiltrates in SSc skin, actively secrete cytokines, and are emerging as a target for novel treatments of SSc.

Dataset Information

Immunosuppressive treatment in diffuse cutaneous systemic sclerosis is associated with an improved composite response index (CRISS).

Publications

Immunosuppressive treatment in diffuse cutaneous systemic sclerosis is associated with an improved composite response index (CRISS).

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