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Previous research discovered a protective effect of higher conscientiousness against a 3-year deterioration in employment status in persons with multiple sclerosis (pwMS). To replicate these findings, we used data from a multicentre prospective cohort study where 145 employed pwMS completed questionnaires, neurological and neuropsychological examinations at baseline and after 3 years. A 3-year deterioration in employment status was reported in 31.0%. We observed no differences in personality, demographics or clinical characteristics between pwMS with deteriorated or stable employment status. These null findings may be partly explained by the classification of deteriorated employment status, which does not reflect Dutch labour conditions. [ABSTRACT FROM AUTHOR]

Purpose: To investigate longitudinal relationships between employment status and disease-related, (neuro)psychological, and work-related factors in people with multiple sclerosis (MS)., Methods: 170 employed people with MS underwent yearly neurological and neuropsychological examinations to assess MS-related disability and cognitive functioning. Additionally, they completed yearly questionnaires assessing depression, anxiety, fatigue, cognitive complaints, workplace support and coping. Multilevel models for change were fitted to examine progression of these factors over three years, and to assess possible relationships with change in employment status., Results: People with a deteriorated employment status after three years reported more depression ( p= 0.009), a higher impact of fatigue ( p< 0.001), more cognitive complaints ( p< 0.001) and less workplace support ( p= 0.001) at baseline than people with a stable employment status. There were no differences in progression over time of the examined variables between people with a stable or deteriorated employment status., Conclusion: More depression, a higher impact of fatigue, more cognitive complaints and less workplace support are predictive of a deteriorated employment status after three years in individuals with MS. How these factors progress over time is not different between those with a stable or deteriorated employment. MS-related disability, anxiety, objective cognition and coping were not related to a deterioration in employment status., Competing Interests: E.E.A. van Egmond, K. van der Hiele, M.J. de Rooij, D.A.M. van Gorp, J.J.L. van der Klink, M.F. Reneman, E.A.C. Beenakker, S.T.F.M. Frequin, K. de Gans, O.H.H. Gerlach, J.P. Mostert, and H.A.M. Middelkoop declare no conflict of interestP.J. Jongen received honoraria from Bayer Netherlands and Orikami Personalized Health Care for consultancy activities and is chairman of the MSmonitor Foundation.L.H. Visser received a research grant for the multicentre BIA study from Merck, received consultancy fees from Merck, Novartis and JanssenJ.J.J. van Eijk received consultancy fees and honoraria for lectures from Merck, Biogen, Novartis, Sanofi, Janssen and RocheE. Hoitsma received honoraria for lectures and advisory boards from Bayer, Biogen, Roche, Sanofi Genzyme, Merck Serono, Novartis and Teva.W.I.M. Verhagen received consultancy fees from Merck and Biogen, (© 2024 The Authors.)

Background: Unemployment is common among people with multiple sclerosis (pwMS) and has been associated with subjective cognitive difficulties, specifically in memory, attention, and executive functioning. However, longitudinal research on subjective cognitive difficulties and employment is scarce., Objective: We investigated whether subjective cognitive impairment (SCI), based on the clinical cut-off score of the MS Neuropsychological Screening Questionnaire (MSNQ), was associated with work status and negative work events (NWE) at baseline and after 2 years. Moreover, we investigated whether four MSNQ subdomains were related to work status and NWE., Methods: 287 participants (77.4% female, median age = 42 years) completed questionnaires on subjective cognitive functioning, depression, anxiety, and fatigue, and completed the Symbol Digit Modalities Test (SDMT). After baseline comparisons, logistic regression analyses were performed, with work status and NWE at baseline, and employment change and NWE change within 2 years after baseline as dependent variables. Independent variables included SCI and the MSNQ domains. Covariates anxiety, depression, fatigue, and SDMT were added., Results: SCI, depression and anxiety were associated with work status ( Nagelkerke R 2 = .286), but only SCI was associated with employment change ( Nagelkerke R 2 = .164). No predictors were associated with NWE at baseline or follow-up. In addition, no MSNQ subdomain was related to work status, employment change or NWE., Conclusion: Unemployed pwMS and pwMS with a deteriorated work status reported more cognitive difficulties after 2 years than employed pwMS or pwMS with a stable work status. In addition, depression, and anxiety were associated with work status., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors.)

Background: Symptoms of anxiety and depression affect the daily life of people with multiple sclerosis (MS). This study examined work difficulties and their relationship with anxiety, depression and coping style in people with MS., Methods: 219 employed people with MS (median age  =  43 years, 79% female) completed questionnaires on anxiety, depression, coping style, demographics and work difficulties, and underwent a neurological examination. Two regression analyses were performed with work difficulties as the dependent variable and either anxiety or depression as continuous independent variables. Coping style, age, gender, educational level, MS-related disability and disease duration were added as additional predictors, as well as interaction terms between coping style and either symptoms of depression or anxiety., Results: A significant model was found ( F (10,205)   =  13.14, p  < 0.001, R 2   =  0.39) in which anxiety, emotion- and avoidance-oriented coping and MS-related disability were positively related to work difficulties. The analysis of depression resulted in a significant model ( F (10,205)   =  14.98, p  < 0.001, R 2   =  0.42) in which depression, emotion- and avoidance-oriented coping and MS-related disability were positively related to work difficulties. None of the interaction effects were significant., Conclusions: Work difficulties were positively related to anxiety, depression, emotion- and avoidance-oriented coping and MS-related disability in workers with MS., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Disclosure: E. van Egmond, K. van der Hiele, D. van Gorp, J. van der Klink, M. Reneman, E. Beenakker, K. de Gans, B.M. van Geel, O. Gerlach, J. Mostert, and H. Middelkoop report no conflict of interest. P. Jongen received honoraria from Bayer Netherlands and Orikami Personalized Health Care, Netherlands, for consultancy activities and is chairman of the MSmonitor foundation, Netherlands. J. van Eijk received honoraria for lectures and honoraria for advisory boards from Sanofi Genzyme, Roche, Merck Serono, Novartis and Teva. S. Frequin received honoraria for lectures, grants for research and honoraria for advisory boards from Sanofi Genzyme, Merck Serono, Novartis, Biogen and Roche. G. Hengstman has received consultation fees and grants from Biogen, BMS, Genzyme-Sanofi, Merck BV, Novartis Pharma and Roche. W. Verhagen received honoraria for lectures from Biogen and Merck Serono, reimbursement for hospitality from Biogen, Sanofi Genzyme and Merck Serono, and honoraria for advisory boards from Merck Serono. L.H. Visser received honoraria for lectures and honoraria for advisory boards from Merck Serono and Novartis., (© The Author(s), 2022.)

Background Aims: To reduce the risk of graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (alloSCT), T-cell depletion (TCD) of grafts can be performed by the addition of alemtuzumab (ALT) "to the bag" (in vitro) before transplantation. In this prospective study, the authors analyzed the effect of in vitro incubation with 20 mg ALT on the composition of grafts prior to graft infusion. Furthermore, the authors assessed whether graft composition at the moment of infusion was predictive for T-cell reconstitution and development of GVHD early after TCD alloSCT., Methods: Sixty granulocyte colony-stimulating factor-mobilized stem cell grafts were obtained from ≥9/10 HLA-matched related and unrelated donors. The composition of the grafts was analyzed by flow cytometry before and after in vitro incubation with ALT. T-cell reconstitution and incidence of severe GVHD were monitored until 12 weeks after transplantation., Results: In vitro incubation of grafts with 20 mg ALT resulted in an initial median depletion efficiency of T-cell receptor (TCR) α/β T cells of 96.7% (range, 63.5-99.8%), followed by subsequent depletion in vivo. Graft volumes and absolute leukocyte counts of grafts before the addition of ALT were not predictive for the efficiency of TCR α/β T-cell depletion. CD4 pos T cells were depleted more efficiently than CD8 pos T cells, and naive and regulatory T cells were depleted more efficiently than memory and effector T cells. This differential depletion of T-cell subsets was in line with their reported differential CD52 expression. In vitro depletion efficiencies and absolute numbers of (naive) TCR α/β T cells in the grafts after ALT incubation were not predictive for T-cell reconstitution or development of GVHD post- alloSCT., Conclusions: The addition of ALT to the bag is an easy, fast and generally applicable strategy to prevent GVHD in patients receiving alloSCT after myeloablative or non-myeloablative conditioning because of the efficient differential depletion of donor-derived lymphocytes and T cells., (Copyright © 2020 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Tumor-associated antigens (TAAs) are monomorphic self-antigens that are proposed as targets for immunotherapeutic approaches to treat malignancies. We investigated whether T cells with sufficient avidity to recognize naturally overexpressed self-antigens in the context of self-HLA can be found in the T-cell repertoire of healthy donors. Minor histocompatibility antigen (MiHA)-specific T cells were used as a model, as the influence of thymic selection on the T-cell repertoire directed against MiHA can be studied in both self (MiHApos donors) and non-self (MiHAneg donors) backgrounds. T-cell clones directed against the HLA*02:01-restricted MiHA HA-1H were isolated from HA-1Hneg/HLA-A*02:01pos and HA-1Hpos/HLA-A*02:01pos donors. Of the 16 unique HA-1H-specific T-cell clones, five T-cell clones derived from HA-1Hneg/HLA-A*02:01pos donors and one T-cell clone derived from an HA-1Hpos/HLA-A*02:01pos donor showed reactivity against HA-1Hpos target cells. In addition, in total, 663 T-cell clones (containing at least 91 unique clones expressing different T-cell receptors) directed against HLA*02:01-restricted peptides of TAA WT1-RMF, RHAMM-ILS, proteinase-3-VLQ, PRAME-VLD, and NY-eso-1-SLL were isolated from HLA-A*02:01pos donors. Only 3 PRAME-VLD-specific and one NY-eso-1-SLL-specific T-cell clone provoked interferon-γ production and/or cytolysis upon stimulation with HLA-A*02:01pos malignant cell lines (but not primary malignant samples) naturally overexpressing the TAA. These results show that self-HLA-restricted T cells specific for self-antigens such as MiHA in MiHApos donors and TAAs are present in peripheral blood of healthy individuals. However, clinical efficacy would require highly effective in vivo priming by peptide vaccination in the presence of proper adjuvants or in vitro expansion of the low numbers of self-antigen-specific T cells of sufficient avidity to recognize endogenously processed antigen., (© 2020 by The American Society of Hematology.)