17 results on '"Larché M"'
Search Results
2. Organic solvent exposure and systemic sclerosis: A retrospective cohort study based on the Canadian Scleroderma Research Group registry
- Author
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Baron, M., Hudson, M., Gyger, G., Pope, J., Larche, M., Khalidi, N., Masetto, A., Sutton, E., Rodriguez Reyna, T.S., Maltez, N., Thorne, C., Fortin, P.R., Ikic, A., Robinson, D., Jones, N., LeClercq, S., Docherty, P., Smith, D., Fritzler, M.J., Kaminska, E., Muntyanu, Anastasiya, Milan, Raymond, Rahme, Elham, Baron, Murray, and Netchiporouk, Elena
- Published
- 2024
- Full Text
- View/download PDF
3. Elevated CD27-IgD- B cells in Post-Acute COVID-19 Sequalae Patients with Rheumatological Symptoms
- Author
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Tan, N S, primary, Zhang, K, additional, Koenig, J F, additional, Somalwar, S, additional, Sedhom, N, additional, Chiu, M N, additional, Jamil, R, additional, Patel, Z, additional, Larché, M, additional, Ho, T, additional, Svenningsen, S, additional, Bowdish, D M, additional, Jordana, M, additional, Tselios, K, additional, and Mukherjee, M, additional
- Published
- 2023
- Full Text
- View/download PDF
4. POS0111 MORE METICULOUSLY FOLLOWING TREAT-TO-TARGET IN RA DOES NOT LEAD TO LESS RADIOGRAPHIC PROGRESSION: A LONGITUDINAL ANALYSIS IN BIODAM
- Author
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Ramiro, S., primary, Landewé, R. B. M., additional, Van der Heijde, D., additional, Sepriano, A., additional, Fitzgerald, O., additional, Østergaard, M., additional, Homik, J., additional, Elkayam, O., additional, Thorne, C., additional, Larché, M., additional, Ferraccioli, G., additional, Backhaus, M., additional, Boire, G., additional, Combe, B., additional, Schaeverbeke, T., additional, Saraux, A., additional, Dougados, M., additional, Rossini, M., additional, Govoni, M., additional, Sinigaglia, L., additional, Cantagrel, A., additional, Allaart, C., additional, Barnabe, C., additional, Bingham, C., additional, Van Schaardenburg, D., additional, Hammer, H. B., additional, Dadashova, R., additional, Hutchings, E., additional, Paschke, J., additional, and Maksymowych, W. P., additional
- Published
- 2022
- Full Text
- View/download PDF
5. Association Between Immunosuppressive Therapy and Incident Risk of Interstitial Lung Disease in Systemic Sclerosis
- Author
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Hoa, Sabrina, primary, Bernatsky, Sasha, additional, Baron, Murray, additional, Proudman, Susanna, additional, Stevens, Wendy, additional, Sahhar, Joanne, additional, Wang, Mianbo, additional, Steele, Russell J., additional, Nikpour, Mandana, additional, Hudson, Marie, additional, Baron, M., additional, Hudson, M., additional, Gyger, G., additional, Hoa, S., additional, Pope, J., additional, Larché, M., additional, Khalidi, N., additional, Masetto, A., additional, Sutton, E., additional, Rodriguez-Reyna, T.S., additional, Maltez, N., additional, Thorne, C., additional, Fortin, P.R., additional, Ikic, A., additional, Robinson, D., additional, Jones, N., additional, LeClercq, S., additional, Mathieu, J.-P., additional, Docherty, P., additional, Smith, D., additional, Fritzler, M., additional, Croyle, L., additional, de Jager, J., additional, Ferdowsi, N., additional, Hill, C., additional, Laurent, R., additional, Lester, S., additional, Major, G., additional, Morrisroe, K., additional, Nash, P., additional, Ngian, G., additional, Nikpour, M., additional, Proudman, S., additional, Rischmueller, M., additional, Roddy, J., additional, Sahhar, J., additional, Schrieber, L., additional, Stevens, W., additional, Strickland, G., additional, Sturgess, A., additional, Thakkar, V., additional, Tymms, K., additional, Walker, J., additional, Youseff, P., additional, and Zochling, J., additional
- Published
- 2021
- Full Text
- View/download PDF
6. One hundred and ten years of Allergen Immunotherapy: A journey from empiric observation to evidence
- Author
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Pfaar, O, Bousquet, J, Durham, S R, Kleine-Tebbe, J, Larché, M, Roberts, G, Shamji, M H, and Gerth van Wijk, R
- Abstract
One hundred and ten years after Noon's first clinical report of the subcutaneous application of allergen extracts, allergen immunotherapy (AIT) has evolved as the most important pillar of the treatment of allergic patients. It is the only disease-modifying treatment option available and the evidence for its clinical efficacy and safety is broad and undisputed. Throughout recent decades, more insights into the underlying mechanisms, in particular the modulation of innate and adaptive immune responses, have been described. AIT is acknowledged by worldwide regulatory authorities, and following the regulatory guidelines for product development, AIT products are subject to a rigorous evaluation before obtaining market authorization. Knowledge and practice are anchored in international guidelines, such as the recently published series of the European Academy of Allergy and Clinical Immunology (EAACI). Innovative approaches continue to be further developed with the focus on clinical improvement by, for example, the usage of adjuvants, peptides, recombinants, modification of allergens, new routes of administration, and the concomitant use of biologicals. In addition, real-life data provide complementary and valuable information on the effectiveness and tolerability of this treatment option in the clinical routine. New mobile health technologies and big-data approaches will improve daily treatment convenience, adherence, and efficacy of AIT. However, the current coronavirus disease 2019 (COVID-19) pandemic has also had some implications for the feasibility and practicability of AIT. Taken together, AIT as the only disease-modifying therapy in allergic diseases has been broadly investigated over the past 110 years laying the path for innovations and further improvement.
- Published
- 2021
7. Damage Trajectories in Systemic Sclerosis Using Group‐BasedTrajectory Modeling
- Author
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Barbacki, Ariane, Baron, Murray, Wang, Mianbo, Zhang, Yuqing, Stevens, Wendy, Sahhar, Joanne, Proudman, Susanna, Nikpour, Mandana, Man, Ada, Baron, M., Hudson, M., Gyger, G., Hoa, S., Pope, J., Larché, M., Khalidi, N., Massetto, A., Sutton, E., Rodriguez‐Reyna, T. S., Maltez, N., Thorne, C., Fortin, P.R., Iki, A., Robinson, D., Jones, N., LeClercq, S., Docherty, P., Smith, D., Fritzler, M., Nikpour, Mandana, Proudman, Susanna, Stevens, Wendy, Sahhar, Joanne, Ferdowsi, Nava, Morrisroe, Kathleen, Ross, Laura, Ngian, Gene‐Siew, Walker, Jennifer, Roddy, Janet, Host, Lauren, and Major, Gabor
- Abstract
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. 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. 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. 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.
- Published
- 2023
- Full Text
- View/download PDF
8. A decade of progress in juvenile idiopathic arthritis treatments and outcomes in Canada: results from ReACCh-Out and the CAPRI registry.
- Author
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Nguyen K, Barsalou J, Basodan D, Batthish M, Benseler SM, Berard RA, Blanchette N, Boire G, Bolaria R, Bruns A, Cabral DA, Cameron B, Campillo S, Cellucci T, Chan M, Chédeville G, Chetaille AL, Chhabra A, Couture J, Dancey P, De Bruycker JJ, Demirkaya E, Dhalla M, Duffy CM, Feldman BM, Feldman DE, Gerschman T, Haddad E, Heale L, Herrington J, Houghton K, Huber AM, Human A, Johnson N, Jurencak R, Lang B, Larché M, Laxer RM, LeBlanc CM, Lee JJY, Levy DM, Lim L, Lim LSH, Luca N, McGrath T, McMillan T, Miettunen PM, Morishita KA, Ng HY, Oen K, Park J, Petty RE, Proulx-Gauthier JP, Ramsey S, Roth J, Rosenberg AM, Rozenblyum E, Rumsey DG, Schmeling H, Schneider R, Scuccimarri R, Shiff NJ, Silverman E, Soon G, Spiegel L, Stringer E, Tam H, Tse SM, Tucker LB, Turvey S, Twilt M, Duffy KW, Yeung RSM, and Guzman J
- Subjects
- Humans, Canada epidemiology, Male, Female, Child, Treatment Outcome, Adolescent, Child, Preschool, Biological Products therapeutic use, Severity of Illness Index, Arthritis, Juvenile drug therapy, Registries, Antirheumatic Agents therapeutic use
- Abstract
Objective: To assess changes in juvenile idiopathic arthritis (JIA) treatments and outcomes in Canada, comparing 2005-2010 and 2017-2021 inception cohorts., Methods: Patients enrolled within three months of diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) and the Canadian Alliance of Pediatric Rheumatology Investigators Registry (CAPRI) cohorts were included. Cumulative incidences of drug starts and outcome attainment within 70 weeks of diagnosis were compared with Kaplan-Meier survival analysis and multivariable Cox regression., Results: The 2005-2010 and 2017-2021 cohorts included 1128 and 721 patients, respectively. JIA category distribution and baseline clinical juvenile idiopathic arthritis disease activity (cJADAS10) scores at enrolment were comparable. By 70 weeks, 6% of patients (95% CI 5, 7) in the 2005-2010 and 26% (23, 30) in the 2017-2021 cohort had started a biologic DMARD (bDMARD), and 43% (40, 47) and 60% (56, 64) had started a conventional DMARD (cDMARD), respectively. Outcome attainment was 64% (61, 67) and 83% (80, 86) for inactive disease (Wallace criteria), 69% (66, 72) and 84% (81, 87) for minimally active disease (cJADAS10 criteria), 57% (54, 61) and 63% (59, 68) for pain control (<1/10), and 52% (47, 56) and 54% (48, 60) for good health-related quality of life (≥9/10)., Conclusion: Although baseline disease characteristics were comparable in the 2005-2010 and 2017-2021 cohorts, cDMARD and bDMARD use increased with a concurrent increase in minimally active and inactive disease. Improvements in parent and patient-reported outcomes were smaller than improvements in disease activity., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2024
- Full Text
- View/download PDF
9. Adding ultrasound to treat-to-target shows no benefit in achieving clinical remission nor in slowing radiographic progression in rheumatoid arthritis: results from a multicenter prospective cohort.
- Author
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Sepriano A, Ramiro S, Landewé R, van der Heijde D, Ohrndorf S, FitzGerald O, Backhaus M, Larché M, Homik J, Saraux A, Hammer HB, Terslev L, Østergaard M, Burmester G, Combe B, Dougados M, Hitchon C, Boire G, Lambert RG, Dadashova R, Paschke J, Hutchings EJ, and Maksymowych WP
- Subjects
- Humans, Female, Male, Middle Aged, Prospective Studies, Aged, Ultrasonography, Treatment Outcome, Adult, Arthritis, Rheumatoid drug therapy, Arthritis, Rheumatoid diagnostic imaging, Disease Progression, Remission Induction, Antirheumatic Agents therapeutic use, Severity of Illness Index, Radiography
- Abstract
Objective: To assess whether using ultrasound (US) in addition to clinical information versus only clinical information in a treat-to-target (T2T) strategy leads to more clinical remission and to less radiographic progression in RA., Methods: Patients with RA from the 2-year prospective BIODAM cohort were included. Clinical and US data (US7-score) were collected every 3 months and hands and feet radiographs every 6 months. At each visit, it was decided whether patients were treated according to the clinical definition of T2T with DAS44 remission as benchmark (T2T-DAS44). T2T-DAS44 was correctly applied if: (i) DAS44 remission had been achieved or (ii) if not, treatment was intensified. A T2T strategy also considering US data (T2T-DAS44-US) was correctly applied if: (i) both DAS44 and US remission (synovitis-score < 2, Doppler-score = 0) were present; or (ii) if not, treatment was intensified. The effect of T2T-DAS44-US on attaining clinical remission and on change in Sharp-van der Heijde score compared to T2T-DAS44 was analysed., Results: A total of 1016 visits of 128 patients were included. T2T-DAS44 was correctly followed in 24% of visits and T2T-DAS44-US in 41%. DAS44 < 1.6 was achieved in 39% of visits. Compared to T2T-DAS44, using the T2T-DAS44-US strategy resulted in a 41% lower likelihood of DAS44 remission [OR (95% CI): 0.59 (0.40;0.87)] and had no effect on radiographic progression [β(95% CI): 0.11 (- 0.16;0.39)] assessed at various intervals up to 12 months later., Conclusion: Our results do not suggest a benefit of using the US7-score in addition to clinical information as a T2T benchmark compared to clinical information alone. Key Points • Ultrasound has a valuable role in diagnostic evaluation of rheumatoid arthritis, but it is unclear whether adding ultrasound to the clinical assessment in a treat-to-target (T2T) strategy leads to more patients achieving remission and reduction in radiographic progression. • Our data from a real-world study demonstrated that adding information from ultrasound to the clinical assessment in a T2T strategy led to a lower rather than a higher likelihood of obtaining clinical remission as compared to using only clinical assessment. • Our data demonstrated that adding ultrasound data to a T2T strategy based only on clinical assessment did not offer additional protection against radiographic progression in patients with RA. • Adding US to a T2T strategy based on clinical assessment led to far more treatment intensifications (with consequences for costs and exposure to adverse events) without yielding a meaningful clinical benefit., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)
- Published
- 2024
- Full Text
- View/download PDF
10. Vertebral Body Reshaping after Fractures: An Important Index of Recovery in Glucocorticoid-Treated Children.
- Author
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Ma J, Siminoski K, Jaremko JL, Koujok K, Matzinger MA, Shenouda N, Wilson N, Cheng M, Alos N, Atkinson S, Cummings EA, Ho J, Rodd C, Sbrocchi AM, Stein R, Barr R, Cairney E, Dix DB, Fernandez CV, Grant R, Halton J, Israels S, Laverdière C, Lewis VA, Cabral DA, Huber A, Houghton K, Jurencak R, Lang B, Larché M, LeBlanc CMA, Miettunen P, Roth J, Scuccimarri R, Bell L, Blydt-Hansen T, Filler G, Feber J, Phan V, Smit K, Rauch F, and Ward LM
- Subjects
- Child, Humans, Glucocorticoids adverse effects, Vertebral Body, Bone Density, Fractures, Bone chemically induced, Spinal Fractures etiology, Spinal Fractures chemically induced, Osteoporotic Fractures chemically induced
- Abstract
Purpose: In this 6-year study we identified factors associated with spontaneous vertebral body reshaping in glucocorticoid (GC)-treated children with leukemia, rheumatic disorders, and nephrotic syndrome., Methods: Subjects were 79 children (mean age 7.4 years) who had vertebral fracture (VF) evaluation on lateral spine radiographs at least 1 year after VF detection. VF were graded using the modified Genant semiquantitative method and fracture burden for individuals was quantified using the spinal deformity index (SDI; sum of grades from T4 to L4)., Results: Sixty-five children (82.3%) underwent complete vertebral body reshaping (median time from VF detection to complete reshaping 1.3 years by Cox proportional hazard modeling). Of 237 VF, the majority (83.1%) ultimately reshaped, with 87.2% reshaping in the thoracic region vs 70.7% in the lumbar region (P = .004). Cox models showed that (1) every g/m2 increase in GC exposure in the first year after VF detection was associated with a 19% decline in the probability of reshaping; (2) each unit increase in the SDI at the time of VF detection was associated with a 19% decline in the probability of reshaping [hazard ratio (HR) = 0.81; 95% confidence interval (CI) = 0.71, 0.92; P = .001]; (3) each additional VF present at the time of VF detection reduced reshaping by 25% (HR = 0.75; 95% CI = 0.62, 0.90; P = .002); and (4) each higher grade of VF severity decreased reshaping by 65% (HR = 0.35; 95% CI = 0.21, 0.57; P < .001)., Conclusion: After experiencing a VF, children with higher GC exposure, higher SDI, more severe fractures, or lumbar VF were at increased risk for persistent vertebral deformity., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2024
- Full Text
- View/download PDF
11. Phase 1 trial supports safety and mechanism of action of peptide immunotherapy for peanut allergy.
- Author
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Voskamp AL, Khosa S, Phan T, DeBerg HA, Bingham J, Hew M, Smith W, Abramovitch J, Rolland JM, Moyle M, Nadeau KC, Lack G, Larché M, Wambre E, O'Hehir RE, Hickey P, and Prickett SR
- Subjects
- Adult, Humans, Desensitization, Immunologic adverse effects, Basophils, Arachis adverse effects, Allergens, Administration, Oral, Peanut Hypersensitivity, Anaphylaxis etiology
- Abstract
Background: Food allergy is a leading cause of anaphylaxis worldwide. Allergen-specific immunotherapy is the only treatment shown to modify the natural history of allergic disease, but application to food allergy has been hindered by risk of severe allergic reactions and short-lived efficacy. Allergen-derived peptides could provide a solution. PVX108 comprises seven short peptides representing immunodominant T-cell epitopes of major peanut allergens for treatment of peanut allergy., Methods: Pre-clinical safety of PVX108 was assessed using ex vivo basophil activation tests (n = 185). Clinical safety and tolerability of single and repeat PVX108 doses were evaluated in a first-in-human, randomized, double-blind, placebo-controlled trial in peanut-allergic adults (46 active, 21 placebo). The repeat-dose cohort received six doses over 16 weeks with safety monitored to 21 weeks. Exploratory immunological analyses were performed at pre-dose, Week 21 and Month 18 after treatment., Results: PVX108 induced negligible activation of peanut-sensitised basophils. PVX108 was safe and well tolerated in peanut-allergic adults. There were no treatment-related hypersensitivity events or AEs of clinical concern. The only events occurring more frequently in active than placebo were mild injection site reactions. Exploratory immunological analyses revealed a decrease in the ratio of ST2
+ Th2A:CCR6+ Th17-like cells within the peanut-reactive Th pool which strengthened following treatment., Conclusion: This study supports the concept that PVX108 could provide a safe alternative to whole peanut immunotherapies and provides evidence of durable peanut-specific T-cell modulation. Translation of these findings to clinical efficacy in ongoing Phase 2 trials would provide important proof-of-concept for using peptides to treat food allergy., (© 2023 Aravax Pty Ltd. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)- Published
- 2024
- Full Text
- View/download PDF
12. Proceedings of the immune thrombocytopenia summit: new concepts in mechanisms, diagnosis, and management.
- Author
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Mahamad S, Modi D, Al-Samkari H, Cuker A, Despotovic JM, Italiano JE, Lambert MP, Lee EJ, Rondina MT, Sholzberg M, Kruse C, Larché M, Nazy I, Miller MS, and Arnold DM
- Abstract
The inaugural McMaster Immune Thrombocytopenia (ITP) Summit was held virually in 2021. The objectives of the Summit were to recognize the difficulties in establishing the diagnosis of ITP and to understand gaps in current knowledge of ITP mechanisms that might lead to better diagnostic approaches and treatments. The half-day program consisted of virtual educational sessions targeting clinicians and basic scientists. The planning committee chose 8 topics to review that would cover current knowledge and inform future research priorities. In this report, we summarized the presentations delivered at the 2021 McMaster ITP Summit and the discussions. Based on the information presented at the Summit, the following research priorities were identified: 1) investigation of platelet production as a target for ITP treatments; 2) characterization of antigen processing and antigen presentation on platelets; 3) interaction between megakaryocytes and the immune system; 4) the role for ITP gene panels; 5) the need for better methods for platelet antibody testing; 6) the role of prediction models for diagnosis and prognosis; 7) new treatment strategies, including intensification of initial therapy; and 8) personalized treatment algorithms., (© 2023 The Authors.)
- Published
- 2023
- Full Text
- View/download PDF
13. One hundred and ten years of Allergen Immunotherapy: A journey from empiric observation to evidence.
- Author
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Pfaar O, Bousquet J, Durham SR, Kleine-Tebbe J, Larché M, Roberts G, Shamji MH, and Gerth van Wijk R
- Subjects
- Allergens, Desensitization, Immunologic, Humans, SARS-CoV-2, COVID-19, Hypersensitivity therapy
- Abstract
One hundred and ten years after Noon's first clinical report of the subcutaneous application of allergen extracts, allergen immunotherapy (AIT) has evolved as the most important pillar of the treatment of allergic patients. It is the only disease-modifying treatment option available and the evidence for its clinical efficacy and safety is broad and undisputed. Throughout recent decades, more insights into the underlying mechanisms, in particular the modulation of innate and adaptive immune responses, have been described. AIT is acknowledged by worldwide regulatory authorities, and following the regulatory guidelines for product development, AIT products are subject to a rigorous evaluation before obtaining market authorization. Knowledge and practice are anchored in international guidelines, such as the recently published series of the European Academy of Allergy and Clinical Immunology (EAACI). Innovative approaches continue to be further developed with the focus on clinical improvement by, for example, the usage of adjuvants, peptides, recombinants, modification of allergens, new routes of administration, and the concomitant use of biologicals. In addition, real-life data provide complementary and valuable information on the effectiveness and tolerability of this treatment option in the clinical routine. New mobile health technologies and big-data approaches will improve daily treatment convenience, adherence, and efficacy of AIT. However, the current coronavirus disease 2019 (COVID-19) pandemic has also had some implications for the feasibility and practicability of AIT. Taken together, AIT as the only disease-modifying therapy in allergic diseases has been broadly investigated over the past 110 years laying the path for innovations and further improvement., (© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
- Published
- 2022
- Full Text
- View/download PDF
14. T cell-mediated autoimmunity in immune thrombocytopenia.
- Author
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Vrbensky JR, Nazy I, Clare R, Larché M, and Arnold DM
- Subjects
- Apoptosis genetics, Apoptosis immunology, Autoantibodies immunology, Autoantigens immunology, Biomarkers, Blood Platelets immunology, Blood Platelets metabolism, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Cytotoxicity, Immunologic, Disease Management, Gene Expression Regulation, Genes, MHC Class I, Humans, Lymphocyte Activation immunology, Purpura, Thrombocytopenic, Idiopathic diagnosis, Purpura, Thrombocytopenic, Idiopathic therapy, T-Lymphocytes metabolism, Autoimmunity, Disease Susceptibility immunology, Purpura, Thrombocytopenic, Idiopathic etiology, T-Lymphocytes immunology
- Abstract
Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by a low platelet count and an increased risk of bleeding. In addition to anti-platelet autoantibodies, CD8
+ T cells have been implicated as a mechanism of platelet destruction. The current evidence for the existence of platelet-specific CD8+ T cells in ITP is inconclusive. The purpose of this review is to summarize the studies that investigated CD8+ T cells in ITP and to review the methods that have been used to detect autoreactive CD8+ T cells in other autoimmune diseases., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)- Published
- 2022
- Full Text
- View/download PDF
15. Technical standards in allergen exposure chambers worldwide - an EAACI Task Force Report.
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Pfaar O, Bergmann KC, Bonini S, Compalati E, Domis N, de Blay F, de Kam PJ, Devillier P, Durham SR, Ellis AK, Gherasim A, Haya L, Hohlfeld JM, Horak F, Iinuma T, Jacobs RL, Jacobi HH, Jutel M, Kaul S, Kelly S, Klimek L, Larché M, Lemell P, Mahler V, Nolte H, Okamoto Y, Patel P, Rabin RL, Rather C, Sager A, Salapatek AM, Sigsgaard T, Togias A, Willers C, Yang WH, Zieglmayer R, Zuberbier T, and Zieglmayer P
- Subjects
- Allergens, Desensitization, Immunologic, Humans, Pollen, Asthma, Rhinitis, Allergic
- Abstract
Allergen exposure chambers (AECs) can be used for controlled exposure to allergenic and non-allergenic airborne particles in an enclosed environment, in order to (i) characterize the pathological features of respiratory diseases and (ii) contribute to and accelerate the clinical development of pharmacological treatments and allergen immunotherapy for allergic disease of the respiratory tract (such as allergic rhinitis, allergic rhinoconjunctivitis, and allergic asthma). In the guidelines of the European Medicines Agency for the clinical development of products for allergen immunotherapy (AIT), the role of AECs in determining primary endpoints in dose-finding Phase II trials is emphasized. Although methodologically insulated from the variability of natural pollen exposure, chamber models remain confined to supporting secondary, rather than primary, endpoints in Phase III registration trials. The need for further validation in comparison with field exposure is clearly mandated. On this basis, the European Academy of Allergy and Clinical Immunology (EAACI) initiated a Task Force in 2015 charged to gain a better understanding of how AECs can generate knowledge about respiratory allergies and can contribute to the clinical development of treatments. Researchers working with AECs worldwide were asked to provide technical information in eight sections: (i) dimensions and structure of the AEC, (ii) AEC staff, (iii) airflow, air processing, and operating conditions, (iv) particle dispersal, (v) pollen/particle counting, (vi) safety and non-contamination measures, (vii) procedures for symptom assessments, (viii) tested allergens/substances and validation procedures. On this basis, a minimal set of technical requirements for AECs applied to the field of allergology is proposed., (© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
- Published
- 2021
- Full Text
- View/download PDF
16. Lasting Changes to Circulating Leukocytes in People with Mild SARS-CoV-2 Infections.
- Author
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Kennedy AE, Cook L, Breznik JA, Cowbrough B, Wallace JG, Huynh A, Smith JW, Son K, Stacey H, Ang J, McGeer A, Coleman BL, Larché M, Larché M, Hambly N, Nair P, Ask K, Miller MS, Bramson J, Levings MK, Nazy I, Svenningsen S, Mukherjee M, and Bowdish DME
- Subjects
- Adult, Aged, Antibodies, Viral, Biomarkers, C-Reactive Protein immunology, C-Reactive Protein metabolism, COVID-19 virology, Cytokines immunology, Female, Humans, Immunophenotyping methods, Inflammation metabolism, Inflammation virology, Lymphocyte Activation, Male, Middle Aged, Respiratory Tract Infections virology, Spike Glycoprotein, Coronavirus immunology, Survivors, T-Lymphocytes immunology, T-Lymphocytes metabolism, Asymptomatic Infections, COVID-19 immunology, Cytokines metabolism, Leukocytes immunology, Leukocytes metabolism, Respiratory Tract Infections immunology, SARS-CoV-2 immunology
- Abstract
Survivors of severe SARS-CoV-2 infections frequently suffer from a range of post-infection sequelae. Whether survivors of mild or asymptomatic infections can expect any long-term health consequences is not yet known. Herein we investigated lasting changes to soluble inflammatory factors and cellular immune phenotype and function in individuals who had recovered from mild SARS-CoV-2 infections ( n = 22), compared to those that had recovered from other mild respiratory infections ( n = 11). Individuals who had experienced mild SARS-CoV-2 infections had elevated levels of C-reactive protein 1-3 months after symptom onset, and changes in phenotype and function of circulating T-cells that were not apparent in individuals 6-9 months post-symptom onset. Markers of monocyte activation, and expression of adherence and chemokine receptors indicative of altered migratory capacity, were also higher at 1-3 months post-infection in individuals who had mild SARS-CoV-2, but these were no longer elevated by 6-9 months post-infection. Perhaps most surprisingly, significantly more T-cells could be activated by polyclonal stimulation in individuals who had recently experienced a mild SARS-CoV-2, infection compared to individuals with other recent respiratory infections. These data are indicative of prolonged immune activation and systemic inflammation that persists for at least three months after mild or asymptomatic SARS-CoV-2 infections.
- Published
- 2021
- Full Text
- View/download PDF
17. Prevalence and trajectory of erosions, synovitis, and bone marrow edema in feet of patients with early rheumatoid arthritis.
- Author
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Ma Z, Zou H, Yelovich MC, Totterman S, Beattie K, and Larché M
- Subjects
- Bone Marrow diagnostic imaging, Edema diagnostic imaging, Edema epidemiology, Humans, Magnetic Resonance Imaging, Prevalence, Arthritis, Rheumatoid complications, Arthritis, Rheumatoid diagnostic imaging, Arthritis, Rheumatoid epidemiology, Synovitis complications, Synovitis diagnostic imaging, Synovitis epidemiology
- Abstract
Despite erosions being as prevalent in feet as in hands in patients with rheumatoid arthritis (RA), their development in relation to synovitis and bone marrow edema (BME) have mainly been studied in hands. This study examines the prevalence and longitudinal trajectory of erosions, BME, and synovitis in metatarsophalangeal joints (MTPJs) in patients with early RA over 2 years of treatment. We also describe correlations between erosions, synovitis, and BME at the joint level. Magnetic resonance imaging (MRI) of the most symptomatic forefoot was acquired at baseline, year 1, and ≥ 2 years. Metatarsophalangeal joints 2-5 were scored by a radiologist for erosions, synovitis, and BME according to OMERACT guidelines. Patients were treated per standard of care. Thirty-two patients with early RA were included. Significant reductions in overall synovitis scores, MTPJ2, and MTPJ3 synovitis scores were seen between year 1 and ≥ 2 years. Overall BME scores improved in year 1 and were sustained at ≥ 2 years. BME improved in MTPJ2, MTPJ3, and MTPJ4. Overall erosions did not significantly change. Positive correlations were seen between changes in synovitis and BME in MTPJ2 and MTPJ5. In patients with early RA, standard of care was associated with overall reductions in synovitis by year 2, BME by year 1, and no progression in overall erosion scores on MRI. MTPJ2 and MTPJ3 appeared to be the most active joints. Improvements in synovitis were noted in MTPJ2 and MTPJ3 and reductions in BME in MTPJ2, MTPJ3, and MTPJ4, while other MTPJs did not progress. Key Points • This is one of the few MRI studies that examined longitudinal changes in imaging outcomes in early RA at the joint level in feet. • Erosions, synovitis, and bone marrow edema (BME) visualized on magnetic resonance imaging were most prevalent in metatarsophalangeal joints (MTPJ) 2 and 3 in patients with early rheumatoid arthritis (RA). • Standard of care was associated with improvements in synovitis in MTPJ2 and MTPJ3 and improvements in BME in MTPJ2, MTPJ3, and MTPJ4 over 2 years of treatment., (© 2021. International League of Associations for Rheumatology (ILAR).)
- Published
- 2021
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