Abstract
Objectives
Damage accrual in SSc can be tracked using the Scleroderma Clinical Trials Consortium Damage Index (DI). Our goal was to develop a prediction model for damage accrual in SSc ...patients with early disease.
Methods
Using patients with <2 years disease duration from Canada and Australia as a derivation cohort, and from the Netherlands as a validation cohort, we used group-based trajectory modelling (GBTM) to determine ‘good’ and ‘bad’ latent damage trajectories. We developed a prediction model from this analysis and applied it to patients from derivation and validation cohorts. We plotted the actual DI trajectories of the patients predicted to be in ‘good’ or ‘bad’ groups.
Results
We found that the actual trajectories of damage accumulation for lcSSc and dcSSc were very different, so we studied each subset separately. GBTM found two distinct trajectories in lcSSc and three in dcSSc. We collapsed the two worse trajectories in the dcSSc into one group and developed a prediction model for inclusion in either ‘good’ or ‘bad’ trajectories. The performance of models using only baseline DI and sex was excellent with ROC AUC of 0.9313 for lcSSc and 0.9027 for dcSSc. Using this model, we determined whether patients would fall into ‘good’ or ‘bad’ trajectory groups and then plotted their actual trajectories which showed clear differences between the predicted ‘good’ and ‘bad’ cases in both derivation and validation cohorts.
Conclusions
A simple model using only cutaneous subset, baseline DI and sex can predict damage accumulation in early SSc.
Objective
Systemic sclerosis (SSc) is an autoimmune disease characterized by progressive organ damage, which can be measured using the Scleroderma Clinical Trials Consortium Damage Index (SCTC‐DI). ...We aimed to identify whether distinct trajectories of damage accrual exist and to determine which variables are associated with different trajectory groups.
Methods
Incident cases of SSc (<2 years) were identified in the Australian Scleroderma Interest Group and Canadian Scleroderma Research Group prospective registries. Group‐based trajectory modeling was used to identify SCTC‐DI trajectories over the cohort's first 5 annual visits. Baseline variables associated with trajectory membership in a univariate analysis were examined in multivariable models.
Results
A total of 410 patients were included. Three trajectory groups were identified: low (54.6%), medium (36.2%), and high (10.3%) damage. Patients with faster damage accrual had higher baseline SCTC‐DI scores. Older age (odds ratio OR 1.57 95% confidence interval (95% CI) 1.18–2.10), male sex (OR 2.55 95% CI 1.10–5.88), diffuse disease (OR 6.7 95% CI 2.57–17.48), tendon friction rubs (OR 5.4 95% CI 1.86–15.66), and elevated C‐reactive protein level (OR 1.98 95% CI 1.49–2.63) increased the odds of being in the high‐damage group versus the reference (low damage), whereas White ethnicity (OR 0.31 95% CI 0.12–0.75) and anticentromere antibodies (OR 0.24 95% CI 0.07–0.77) decreased the odds.
Conclusion
We identified 3 trajectories of damage accrual in a combined incident SSc cohort. Several characteristics increased the odds of belonging to worse trajectories. These findings may be helpful in recognizing patients in whom early aggressive treatment is necessary.
Specific allergen immunotherapy has been widely practised for almost 100 years. Whilst this approach is disease-modifying and efficacious, the use of whole allergen preparations is associated with an ...unacceptably high prevalence of allergic adverse events during treatment. Many approaches to reduce the allergenicity of immunotherapy preparations whilst maintaining immunogenicity are under development. One such approach is the use of short synthetic peptides which represent major T-cell epitopes of the allergen. Major potential advantages of this approach include markedly reduced capacity to cross-link immunoglobulin-E and activate mast cells and basophils, and ease of manufacture and standardization. Promising results in preclinical studies have led to the translation of this approach to clinical studies in humans. Peptide immunotherapy is currently under development for allergic and autoimmune diseases. PUBLICATION ABSTRACT
In clinical studies, cat allergic individuals treated with intradermal administration of synthetic peptides containing T cell epitopes of the major cat allergen Feld1, experienced reduced sensitivity ...to allergen challenge in the skin, nose and lung.
Background: IL-5-producing allergen-specific T cells are thought to play a prominent role in the pathogenesis of allergic inflammation. We hypothesized that T cell allergen-driven IL-5 synthesis is ...elevated in patients with atopic disease as compared with that in atopic patients free of disease and nonatopic control subjects.
Objectives: The purpose of this study was to compare IL-5 and interferon-γ (IFN-γ) secretion and proliferation by peripheral blood T cells from sensitized atopic patients with asthma, rhinitis, and no symptoms and from nonatopic control subjects in response to the allergen
Dermatophagoides pteronyssinus (Der p) and the control recall antigen
Mycobacterium tuberculosis purified protein derivative (PPD).
Methods: To measure allergen-induced IL-5 production and proliferation, we developed a short-term culture technique that required a single antigenic stimulation of freshly isolated peripheral blood mononuclear cells (PBMC). With this technique, we measured Der p- and PPD-induced IL-5 production and proliferation in PBMC from atopic patients with asthma who were allergic to Der p, atopic patients with rhinitis, atopic patients with no symptoms, and a group of nonatopic normal control subjects. In four experiments, CD4+ or CD8+ T cells were depleted from PBMC to confirm that IL-5 synthesis was T cell dependent.
Results: T cell IL-5 production, but not IFN-γ production, in response to Der p was elevated in atopic patients with asthma and atopic patients with rhinitis compared with findings in atopic patients with no symptoms or nonatopic control subjects. IL-5 production was abrogated by depletion of CD4+, but not CD8+, T cells. In subjects with asthma, allergen-driven IL-5 production correlated with bronchial hyperreactivity. Allergen-induced proliferation was also higher in patients with asthma than in atopic subjects with no symptoms or nonatopic controls. T cell IL-5 and IFN-γ production and proliferation in response to PPD were similar regardless of atopic status or disease.
Conclusions: Elevated IL-5 production is a characteristic of allergen-specific peripheral blood CD4+ T cells from sensitized patients with atopic disease but not atopy per se. (J Allergy Clin Immunol 1997;99:563-9.)
Conventional immunotherapy using whole allergen extracts has been shown to be an effective, disease-modifying treatment in carefully selected patients with allergic conjunctivo-rhinitis, asthma and ...bee and wasp venom hypersensitivity. However, this form of therapy is associated with the risk of systemic anaphylaxis, which, when severe, can be life threatening. A potentially significant reduction in the incidence of IgE-mediated events during immunotherapy may be achieved by the use of short peptides corresponding to T cell epitopes which, by virtue of their size, are incapable of cross-linking allergen-specific IgE bound to the surface of mast cells and basophils. Initial clinical studies have demonstrated degrees of efficacy which have, in some cases, been associated with adverse events occurring immediately or several hours after peptide administration. Preliminary data from studies employing shorter peptides (20 amino acids or less) suggest that improved efficacy may be achieved by using peptides of defined major histocompatibility complex-binding specificity administered in an incremental dose fashion comparable to conventional immunotherapy. This review will discuss the concept of peptide immunotherapy and the implications of recent studies.
Abstract Context Pain and itch are common symptoms reported by patients with scleroderma (SSc), which can markedly diminish function and health-related quality of life (HRQL). Objectives The aim of ...this exploratory study was to examine the impact that pain, itch, and the interaction of both, have on function (depressive symptoms, overall disability, fatigue, sleep disturbance) and HRQL in patients with SSc. Methods A total of 964 patients from the Canadian Scleroderma Research Group Registry completed questionnaires measuring itch and pain severity, function, and HRQL. Multiple regression analyses were performed to examine the impact that pain, itch and pain*itch interaction have on each outcome variable while controlling for demographic measures. A P -value of ≤ 0.01 was required for a difference to be deemed statistically significant. Results Our results revealed that patients with SSc who reported higher pain and itch severity were also more likely to have greater depressive symptoms, overall disability, sleep and fatigue problems, even when demographic measures were controlled for ( P -values ≤ 0.001). Similar results were obtained for HRQL, regardless of the domains ( P -values ≤ 0.001). A significant association between pain*itch interaction and sleep ( P = 0.002), physical functioning ( P = 0.003) and general health ( P ≤ 0.001) variables also was found. Further investigation of the nature of the pain*itch interaction showed that the effect of pain severity on outcome variables diminishes as itch severity increases. Conclusion Both pain and itch appear to have a detrimental impact on functioning and HRQL in patients with SSc, suggesting that more targeted approaches to symptom management are warranted.
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