10 research outputs found

    Single-cell characterization of dog allergen–specific T cells reveals TH2 heterogeneity in allergic individuals

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    BackgroundAllergen-specific type 2 CD4+ TH2 cells are critically involved in the pathogenesis of IgE-mediated allergic diseases. However, the heterogeneity of the TH2 response has only recently been appreciated.ObjectiveWe sought to characterize at the single-cell level the ex vivo phenotype, transcriptomic profile, and T-cell receptor (TCR) repertoire of circulating CD4+ T cells specific to the major dog allergens Can f 1, Can f 4, and Can f 5 in subjects with and without dog allergy.MethodsDog allergen–specific memory CD4+ T cells were detected ex vivo by flow cytometry using a CD154-based enrichment assay and single-cell sorted for targeted gene expression analysis and TCR sequencing.ResultsDog allergen–specific T-cell responses in allergic subjects were dominantly of TH2 type. TH2 cells could be phenotypically further divided into 3 subsets, which consisted of TH2-like (CCR6−CXCR3−CRTH2−), TH2 (CCR6−CXCR3−CRTH2+CD161−), and TH2A (CCR6−CXCR3−CRTH2+CD161+CD27−) cells. All these subsets were nonexistent within the allergen-specific T-cell repertoire of healthy subjects. Single-cell transcriptomic profiling confirmed the TH2-biased signature in allergen-specific T cells from allergic subjects and revealed a TH1/TH17 signature in nonallergic subjects. TCR repertoire analyses showed that dog allergen–specific T cells were diverse and allergic subjects demonstrated less clonality compared to nonallergic donors. Finally, TCR and transcriptomic analyses revealed a close relationship between TH2-like, TH2, and TH2A cells, with the last ones representing the most terminally differentiated and highly polarized subtype.ConclusionsOur study demonstrates heterogeneity within allergen-specific TH2 cells at the single-cell level. The results may be utilized for improving immune monitoring after allergen immunotherapy and for designing targeted immunomodulatory approaches.</p

    Patients with Hidradenitis Suppurativa Suffer from Low Health-Related Quality of Life as Measured by the Generic 15D Instrument

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    Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with various comorbidities and diminished quality of life (QoL). Among dermatological conditions, HS is reported to most severely diminish QoL. This study aimed to analyse the health-related QoL (HRQoL) of patients with HS in more detail by using generic to disease-specific HRQoL questionnaires. Correlations between the HRQoL measures and HS disease severity measures were assessed. Methods: We analysed the HRQoL and clinical severity of patients with HS (N = 92) treated in 5 Finnish hospitals using HRQoL measurement tools most often used in dermatological clinics, as well as the generic 15D instrument (standardized and self-administered 15-dimensional measure of HRQoL). The disease severity was assessed using the Hurley stage, International Hidradenitis Suppurativa Severity Score System, and disease severity evaluation by the investigator. Results: The mean 15D score of HS patients was low and comparable with that of patients with cancers. No correlation was found between HS severity measures and 15D score, indicating that even mild HS has a high impact on HRQoL. Conclusions: Our findings strengthen the understanding about HS as a debilitating disease and even compared with non-dermatological conditions and highlight the need of comprehensive care of patients with HS.</p

    Patients with Hidradenitis Suppurativa Suffer from Low Health-Related Quality of Life as Measured by the Generic 15D Instrument

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    Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with various comorbidities and diminished quality of life (QoL). Among dermatological conditions, HS is reported to most severely diminish QoL. This study aimed to analyse the health-related QoL (HRQoL) of patients with HS in more detail by using generic to disease-specific HRQoL questionnaires. Correlations between the HRQoL measures and HS disease severity measures were assessed. Methods: We analysed the HRQoL and clinical severity of patients with HS (N = 92) treated in 5 Finnish hospitals using HRQoL measurement tools most often used in dermatological clinics, as well as the generic 15D instrument (standardized and self-Administered 15-dimensional measure of HRQoL). The disease severity was assessed using the Hurley stage, International Hidradenitis Suppurativa Severity Score System, and disease severity evaluation by the investigator. Results: The mean 15D score of HS patients was low and comparable with that of patients with cancers. No correlation was found between HS severity measures and 15D score, indicating that even mild HS has a high impact on HRQoL. Conclusions: Our findings strengthen the understanding about HS as a debilitating disease and even compared with non-dermatological conditions and highlight the need of comprehensive care of patients with HS.publishedVersionPeer reviewe

    Cervical squamous carcinoma cells are resistant to the combined action of tumor necrosis factor-α and histamine whereas normal keratinocytes undergo cytolysis

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    <p>Abstract</p> <p>Background</p> <p>Previous reports showed that mast cells can typically be found in the peritumoral stroma of cervix carcinomas as well as in many other cancers. Both histamine and TNF-α are potent preformed mast cell mediators and they can act simultaneously after release from mast cells. Thus, the effect of TNF-α and histamine on cervical carcinoma cell lines was studied.</p> <p>Methods and results</p> <p>TNF-α alone induced slight growth inhibition and cell cycle arrest at G0/G1 phase in SiHa cells, but increased their migration. Histamine alone had no effect on cells. In addition, TNF-α and histamine in combination showed no additional effect over that by TNF-α alone, although SiHa cells were even pretreated with a protein synthesis inhibitor. Furthermore, TNF-α-sensitive ME-180 carcinoma cells were also resistant to the combination effect of TNF-α and histamine. In comparison, TNF-α or histamine alone induced growth inhibition in a non-cytolytic manner in normal keratinocytes, an effect that was further enhanced to cell cytolysis when both mediators acted in combination. Keratinocytes displayed strong TNF receptor (TNFR) I and II immunoreactivity, whereas SiHa and ME-180 cells did not. Furthermore, cervix carcinoma specimens revealed TNF-α immunoreactivity in peritumoral cells and carcinoma cells. However, the immunoreactivity of both TNFRs was less intense in carcinoma cells than that in epithelial cells in cervical specimens with non-specific inflammatory changes.</p> <p>Conclusion</p> <p>SiHa and ME-180 cells are resistant to the cytolytic effect of TNF-α and histamine whereas normal keratinocytes undergo cytolysis, possibly due to the smaller amount of TNFRs in SiHa and ME-180 cells. In the cervix carcinoma, the malignant cells may resist this endogenous cytolytic action and TNF-α could even enhance carcinoma cell migration.</p

    Guselkumab Treatment Outcomes and Persistence in a Nationwide Real-world Cohort of Patients with Plaque Psoriasis

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    Guselkumab treatment outcomes and persistence were assessed in a real-world cohort of Finnish patients with difficult-to-treat plaque psoriasis over a median follow-up of 1 year. Data on 181 patients who initiated guselkumab at the 15 study centres were collected retrospectively from the patient charts. Prior exposure to biologic therapies was common, with 56% and 35% having used at least 1 and 2 biologics, respectively. Median guselkumab treatment duration was 11 months with 21 patients (12%) discontinuing treatment during follow-up. Of 85 patients with a follow-up duration of at least 1 year, 73 (86%) were still on guselkumab at 1 year. Significant improvements during follow-up were seen in the absolute Psoriasis Area and Severity Index (PASI) scores with 32 patients (80%) having absolute PASI ≀ 2 after a 9–14-month treatment. Guselkumab treatment was effective and treatment persistence was high in the nationwide Finnish real-life setting.</p

    Guselkumab Treatment Outcomes and Persistence in a Nationwide Real-world Cohort of Patients with Plaque Psoriasis

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    Guselkumab treatment outcomes and persistence were assessed in a real-world cohort of Finnish patients with difficult-to-treat plaque psoriasis over a median follow-up of 1 year. Data on 181 patients who initiated guselkumab at the 15 study centres were collected retrospectively from the patient charts. Prior exposure to biologic therapies was common, with 56% and 35% having used at least 1 and 2 biologics, respectively. Median guselkumab treatment duration was 11 months with 21 patients (12%) discontinuing treatment during follow-up. Of 85 patients with a follow-up duration of at least 1 year, 73 (86%) were still on guselkumab at 1 year. Significant improvements during follow-up were seen in the absolute Psoriasis Area and Severity Index (PASI) scores with 32 patients (80%) having absolute PASI ≀ 2 after a 9–14-month treatment. Guselkumab treatment was effective and treatment persistence was high in the nationwide Finnish real-life setting.publishedVersionPeer reviewe

    Clinical, patient and estimated cost benefits of proactive management versus reactive management with calcipotriol/betamethasone dipropionate foam for the treatment of plaque psoriasis in Finland

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    Background Proactive management of plaque psoriasis with twice-weekly topical calcipotriol/betamethasone dipropionate (Cal/BD) foam has a demonstrated clinical benefit in preventing disease relapse compared to reactive management, where Cal/BD foam is only given as rescue therapy once-daily for four weeks after relapse. The impact of proactive management with Cal/BD foam on a wider range of clinical responses is not yet known, nor is its potential cost-effectiveness in the healthcare system of Finland. Methods This study involved a post-hoc analysis exploring the clinical and patient-reported benefits of proactive versus reactive management with Cal/BD foam observed in the PSO-LONG trial (NCT02899962). A range of response criteria based on modified psoriasis area and severity index (mPASI) and dermatology life quality index (DLQI) were analyzed, and the cost-effectiveness of proactive versus reactive management was estimated in a Finnish healthcare setting. Results and conclusion The analysis found a consistent clinical benefit of proactive management compared to reactive management on all response criteria, and a markedly lower cost-per-responder for the response criteria of mPASI 75, mPASI ≀ 2 and DLQ1 ≀ 1. The analysis was robust to sensitivity analyses on key inputs and demonstrates the cost and clinical benefits of proactive over reactive management of plaque psoriasis with Cal/BD foam in the Finnish healthcare setting

    Guselkumab treatment outcomes and persistence in a nationwide real-world cohort of patients with plaque psoriasis

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    Abstract Guselkumab treatment outcomes and persistence were assessed in a real-world cohort of Finnish patients with difficult-to-treat plaque psoriasis over a median follow-up of 1 year. Data on 181 patients who initiated guselkumab at the 15 study centres were collected retrospectively from the patient charts. Prior exposure to biologic therapies was common, with 56% and 35% having used at least 1 and 2 biologics, respectively. Median guselkumab treatment duration was 11 months with 21 patients (12%) discontinuing treatment during follow-up. Of 85 patients with a follow-up duration of at least 1 year, 73 (86%) were still on guselkumab at 1 year. Significant improvements during follow-up were seen in the absolute Psoriasis Area and Severity Index (PASI) scores with 32 patients (80%) having absolute PASI ≀ 2 after a 9–14-month treatment. Guselkumab treatment was effective and treatment persistence was high in the nationwide Finnish real-life setting
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