Engaging a community to focus on upper limb function in people with multiple sclerosis: the ThinkHand campaign case study.

BACKGROUND: Solving complex research challenges requires innovative thinking and alternative approaches to traditional methods. One such example is the problem of arm and hand, or upper limb function in multiple sclerosis (MS), a neurological condition affecting approximately 2.9 million people worldwide and more than 150,000 in the United Kingdom. Historically, clinical trials and research have focused on mobility and walking ability. This excludes a large number of patients who are wheelchair users, limiting their quality of life and restricting access to possibly helpful medications. To address this issue, the ThinkHand campaign was launched in 2016, aiming to raise awareness about the importance of upper limb function in MS and develop alternative ways to measure, record, and account for hand and arm function changes. MAIN BODY: The campaign utilised innovative strategies at scientific conferences and online surveys to engage people affected by MS, healthcare professionals, charities, and researchers in discussing the importance of preserving upper limb function. Through co-design and interdisciplinary collaboration, the campaign developed new tools like the low-cost cardboard version of the Nine-Hole Peg Test, facilitating remote monitoring of hand function. Additionally, the campaign co-created the "Under & Over" rehabilitation tool, allowing individuals with advanced MS to participate in a remote rehabilitation program.The impact of the ThinkHand campaign has been significant, helping to shift the focus of both academic and industry-supported trials, including the O'HAND and ChariotMS trials, both using upper limb function as their primary end point. The campaign's patient-centred approach highlighted the importance of recognising patients' perspectives in research and challenged established assumptions and practices. It demonstrated the effectiveness of interdisciplinary collaboration, systems thinking, and co-creation with stakeholders in tackling complex problems. CONCLUSION: The ThinkHand campaign provides valuable insights for health research practices. By involving patients at all stages, researchers can gain a deeper understanding of the impact of disease on their lives, identify gaps and focus research on their needs. Experimentation and iteration can lead to innovative solutions, and openness to unconventional methods can drive widespread change. The ThinkHand campaign exemplifies the potential of patient-centred approaches to address complex research challenges and revolutionise the field of MS research and management. Embracing such approaches will contribute to more inclusive and impactful research in the future.

Solving complex research challenges requires creative thinking and new ways of doing things. One such challenge is understanding the problems with arm and hand function in multiple sclerosis (MS), a neurological condition that affects more than 150,000 in the United Kingdom. In the past, research focused mainly on walking ability, leaving out many people who use wheelchairs.To tackle this issue, we created the ThinkHand campaign in 2016. Its goal was to raise awareness about the importance of hand and arm function for people with MS (pwMS) and find better ways to measure changes in these functions such that they can become outcomes in clinical trials. This could provide a pathway to better treatments for pwMS who cannot walk.The campaign used various methods, including surveys, social media posts, exhibitions and music to involve pwMS, healthcare professionals, charities, and researchers in discussions about the issues. Working together, they created tools to support pwMS, particularly those at an advanced stage of the disease (pwAMS), to take part in research and measure their hand and arm function. Through our collaborative approach focusing on patients' perspectives, the campaign challenged old ideas and deeply embedded practices. It showed that collaboration between different areas of expertise involving pwMS at all stages of research can help solve complex problems. This campaign teaches us valuable lessons for health research. When researchers listen to patients and try new things, they can better understand how a disease affects people's lives and develop better solutions.In conclusion, we show how embracing a patient-centred approach can address complex research challenges and improve how we study and manage MS and other conditions in the future.

Neutropenia following immune-depletion, notably CD20 targeting, therapies in multiple sclerosis.

Neutropenia serves as a risk factor for severe infection and is a consequence of some immune-depleting immunotherapies. This occurs in people with multiple sclerosis following chemotherapy-conditioning in haematopoietic stem cell transplantation and potent B cell targeting agents. Whilst CD52 is expressed by neutrophils and may contribute to early-onset neutropenia following alemtuzumab treatment, deoxycytidine kinase and CD20 antigen required for activity of cladribine tablets, off-label rituximab, ocrelizumab, ofatumumab and ublituximab are not or only weakly expressed by neutrophils. Therefore, alternative explanations are needed for the rare occurrence of early and late-onset neutropenia following such treatments. This probably occurs due to alterations in the balance of granulopoiesis and neutrophil removal. Neutrophils are short-lived, and their removal may be influenced by drug-associated infections, the killing mechanisms of the therapies and amplified by immune dyscrasia due to influences on neutropoiesis following growth factor rerouting for B cell recovery and cytokine deficits following lymphocyte depletion. This highlights the small but evident neutropenia risks following sustained B cell depletion with some treatments.

Disease activity 4.5 years after starting cladribine: experience in 264 patients with multiple sclerosis.

Background: Cladribine is an effective immunotherapy for people with multiple sclerosis (pwMS). Whilst most pwMS do not require re-treatment following standard dosing (two treatment courses), disease activity re-emerges in others. The characteristics of pwMS developing re-emerging disease activity remain incompletely understood. Objectives: To explore whether clinical and/or paraclinical baseline characteristics, including the degree of lymphocyte reduction, drug dose and lesions on magnetic resonance imaging (MRI) are associated with re-emerging disease activity. Design: Service evaluation in pwMS undergoing subcutaneous cladribine (SClad) treatment. Methods: Demographics, clinical, laboratory and MRI data of pwMS receiving two courses of SClad were extracted from health records. To assess associations of predictor variables with re-emerging disease activity, a series of Cox proportional hazards models was fitted (one for each predictor variable). Results: Of n = 264 pwMS 236 received two courses of SClad and were included in the analysis. Median follow-up was 4.5 years (3.9, 5.3) from the first, and 3.5 years (2.9, 4.3) from the last SClad administration. Re-emerging disease activity occurred in 57/236 pwMS (24%); 22/236 received further cladribine doses (SClad or cladribine tablets) at 36.7 months [median; interquartile range (IQR): 31.7, 42.1], and 22/236 other immunotherapies 18.9 months (13.0, 30.2) after their second course of SClad, respectively. Eligibility was based on MRI activity in 29, relapse in 5, both in 13, elevated cerebrospinal fluid neurofilament light chain level in 3, deterioration unrelated to relapse in 4 and other in 3. Only 36/57 of those eligible for additional immunotherapy had received a reduced dose of SClad for their second treatment course. Association was detected between re-emerging disease activity and (i) high baseline MRI activity and (ii) low second dose of SClad. Conclusion: Re-emerging disease activity was associated with baseline MRI activity and low dose second course of SClad.

Parakinesia Brachialis Oscitans in a Patient With a First Manifestation of Multiple Sclerosis.

Objectives: Parakinesia brachialis oscitans (PBO) is the involuntary movement of an otherwise paretic upper limb triggered by yawning. We describe the first case of PBO in a patient with a first manifestation of tumefactive multiple sclerosis (MS). Methods: A 35-year-old man presented to the emergency department with a first episode of generalized seizure. Neurologic examination revealed left-sided spastic hemiparesis, predominantly affecting his upper limb. Brain MRI showed a tumefactive right hemisphere lesion consistent with demyelination. CSF did not document unmatched oligoclonal bands. Results: Two weeks after admission and, despite being unable to voluntarily raise his left arm, the patient noticed a repeated and reproducible involuntary raise of this limb upon yawning, consistent with PBO. In the following weeks, the phenomenon diminished both in frequency and movement amplitude alongside motor recovery. An MRI performed 2 months later showed progression of the demyelinating lesion load and confirmed a diagnosis of MS. Discussion: PBO is an example of autonomic voluntary motor dissociation and reflects the interplay between loss of cortical inhibition of the cerebellum in the setting of functional spinocerebellar pathways. Clinicians should be aware of this transient phenomenon which should not be mistaken as a chronic movement disorder or focal epileptic seizures.

Risk of COVID-19 in people with multiple sclerosis who are seronegative following vaccination.

BACKGROUND: People with multiple sclerosis (pwMS) treated with certain disease-modifying therapies (DMTs) have attenuated IgG response following COVID-19 vaccination; however, the clinical consequences remain unclear. OBJECTIVE: To report COVID-19 rates in pwMS according to vaccine serology. METHODS: PwMS with available (1) serology 2-12 weeks following COVID-19 vaccine 2 and/or vaccine 3 and (2) clinical data on COVID-19 infection/hospitalisation were included. Logistic regression was performed to examine whether seroconversion following vaccination predicted risk of subsequent COVID-19 infection after adjusting for potential confounders. Rates of severe COVID-19 (requiring hospitalisation) were also calculated. RESULTS: A total of 647 pwMS were included (mean age 48 years, 500 (77%) female, median Expanded Disability Status Scale (EDSS) 3.5% and 524 (81%) exposed to DMT at the time of vaccine 1). Overall, 472 out of 588 (73%) were seropositive after vaccines 1 and 2 and 222 out of 305 (73%) after vaccine 3. Seronegative status after vaccine 2 was associated with significantly higher odds of subsequent COVID-19 infection (odds ratio (OR): 2.35, 95% confidence interval (CI): 1.34-4.12, p = 0.0029), whereas seronegative status after vaccine 3 was not (OR: 1.05, 95% CI: 0.57-1.91). Five people (0.8%) experienced severe COVID-19, all of whom were seronegative after most recent vaccination. CONCLUSION: Attenuated humoral response to initial COVID-19 vaccination predicts increased risk of COVID-19 in pwMS, but overall low rates of severe COVID-19 were seen.

Decision Making About Disease-Modifying Treatments for Relapsing-Remitting Multiple Sclerosis: Stated Preferences and Real-World Choices.

BACKGROUND: People with relapsing-remitting multiple sclerosis can benefit from disease-modifying treatments (DMTs). Several DMTs are available that vary in their efficacy, side-effect profile and mode of administration. OBJECTIVE: We aimed to measure the preferences of people with relapsing-remitting multiple sclerosis for DMTs using a discrete choice experiment and to assess which stated preference attributes correlate with the attributes of the DMTs they take in the real world. METHODS: Discrete choice experiment attributes were developed from literature reviews, interviews and focus groups. In a discrete choice experiment, participants were shown two hypothetical DMTs, then chose whether they preferred one of the DMTs or no treatment. A mixed logit model was estimated from responses and individual-level estimates of participants' preferences conditional on their discrete choice experiment choices calculated. Logit models were estimated with stated preferences predicting current real-world on-treatment status, DMT mode of administration and current DMT. RESULTS: A stated intrinsic preference for taking a DMT was correlated with currently taking a DMT, and stated preferences for mode of administration were correlated with the modes of administration of the DMTs participants were currently taking. Stated preferences for treatment effectiveness and adverse effects were not correlated with real-world behaviour. CONCLUSIONS: There was variation in which discrete choice experiment attributes correlated with participants' real-world DMT choices. This may indicate patient preferences for treatment efficacy/risk are not adequately taken account of in prescribing. Treatment guidelines must ensure they take into consideration patients' preferences and improve communication around treatment efficacy/risk.

A plain language summary of the impact of vaccines against flu and chickenpox in people with multiple sclerosis treated with cladribine tablets.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of an article originally published in the Multiple Sclerosis Journal. Cladribine tablets (MAVENCLAD®) are an oral (taken by mouth) medication, approved for the treatment of people with relapsing forms of multiple sclerosis (MS, with episodes of new or worsening symptoms). They are administered for a maximum of 10 days per year, over a period of 2 years. Cladribine tablets work by temporarily reducing the number of lymphocytes, which are immune cells that help to fight off infections. Because of this, people with MS (also called PwMS) may have concerns about the effect of cladribine tablets on vaccines, as these work via immune cells to build protection against infection. WHAT HAPPENED IN THE MAGNIFY-MS STUDY?: A study called MAGNIFY-MS investigated how long it takes for cladribine tablets to begin to work in people with a type of MS called highly active relapsing MS. During the study, some participants received their usual vaccinations against flu (influenza) and against the chickenpox virus (also called varicella zoster virus) as part of their routine medical care. The MAGNIFY-MS study gave the researchers an opportunity to look at how cladribine tablets affect the way the flu and chickenpox virus vaccines work in the body. WHAT WERE THE RESULTS?: Cladribine tablets do not affect how well the body responds to flu and chickenpox vaccines. WHAT DO THE RESULTS MEAN?: PwMS taking cladribine tablets who are vaccinated against chickenpox, flu or both can be protected against these diseases.

The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination.

BACKGROUND: Sphingosine-one phosphate receptor (S1PR) modulation inhibits S1PR1-mediated lymphocyte migration, lesion formation and positively-impacts on active multiple sclerosis (MS). These S1PR modulatory drugs have different: European Union use restrictions, pharmacokinetics, metabolic profiles and S1PR receptor affinities that may impact MS-management. Importantly, these confer useful properties in dealing with COVID-19, anti-viral drug responses and generating SARS-CoV-2 vaccine responses. OBJECTIVE: To examine the biology and emerging data that potentially underpins immunity to the SARS-CoV-2 virus following natural infection and vaccination and determine how this impinges on the use of current sphingosine-one-phosphate modulators used in the treatment of MS. METHODS: A literature review was performed, and data on infection, vaccination responses; S1PR distribution and functional activity was extracted from regulatory and academic information within the public domain. OBSERVATIONS: Most COVID-19 related information relates to the use of fingolimod. This indicates that continuous S1PR1, S1PR3, S1PR4 and S1PR5 modulation is not associated with a worse prognosis following SARS-CoV-2 infection. Whilst fingolimod use is associated with blunted seroconversion and reduced peripheral T-cell vaccine responses, it appears that people on siponimod, ozanimod and ponesimod exhibit stronger vaccine-responses, which could be related notably to a limited impact on S1PR4 activity. Whilst it is thought that S1PR3 controls B cell function in addition to actions by S1PR1 and S1PR2, this may be species-related effect in rodents that is not yet substantiated in humans, as seen with bradycardia issues. Blunted antibody responses can be related to actions on B and T-cell subsets, germinal centre function and innate-immune biology. Although S1P1R-related functions are seeming central to control of MS and the generation of a fully functional vaccination response; the relative lack of influence on S1PR4-mediated actions on dendritic cells may increase the rate of vaccine-induced seroconversion with the newer generation of S1PR modulators and improve the risk-benefit balance IMPLICATIONS: Although fingolimod is a useful asset in controlling MS, recently-approved S1PR modulators may have beneficial biology related to pharmacokinetics, metabolism and more-restricted targeting that make it easier to generate infection-control and effective anti-viral responses to SARS-COV-2 and other pathogens. Further studies are warranted.

Specific Patterns of Immune Cell Dynamics May Explain the Early Onset and Prolonged Efficacy of Cladribine Tablets: A MAGNIFY-MS Substudy.

BACKGROUND AND OBJECTIVES: Cladribine tablets cause a reduction in lymphocytes with a predominant effect on B-cell and T-cell counts. The MAGNIFY-MS substudy reports the dynamic changes on multiple peripheral blood mononuclear cell (PBMC) subtypes and immunoglobulin (Ig) levels over 12 months after the first course of cladribine tablets in patients with highly active relapsing multiple sclerosis (MS). METHODS: Immunophenotyping was performed at baseline (predose) and at the end of months 1, 2, 3, 6, and 12 after initiating treatment with cladribine tablets. Assessments included lymphocyte subtype counts of CD19+ B cells, CD4+ and CD8+ T cells, CD16+ natural killer cells, plasmablasts, and Igs. Immune cell subtypes were analyzed by flow cytometry, and serum IgG and IgM were analyzed by nephelometric assay. Absolute cell counts and percentage change from baseline were assessed. RESULTS: The full analysis set included 57 patients. Rapid reductions in median CD19+, CD20+, memory, activated, and naive B-cell counts were detected, reaching nadir by month 2. Thereafter, total CD19+, CD20+, and naive B-cell counts subsequently reconstituted, but memory B cells remained reduced by 93%-87% for the remainder of the study. The decrease in plasmablasts was slower, reaching nadir at month 3. Decrease in T-cell subtypes was also slower and more moderate compared with B-cell subtypes, reaching nadir between months 3 and 6. IgG and IgM levels remained within the normal range over the 12-month study period. DISCUSSION: Cladribine tablets induce a specific pattern of early and sustained PBMC subtype dynamics in the absence of relevant Ig changes: While total B cells were reduced dramatically, T cells were affected significantly less. Naive B cells recovered toward baseline, naive CD4 and CD8 T cells did not, and memory B cells remained reduced. The results help to explain the unique immune depletion and repopulation architecture regarding onset of action and durability of effects of cladribine tablets while largely maintaining immune competence. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03364036. Date registered: December 06, 2017.

MS care: integrating advanced therapies and holistic management.

Lifestyle and environmental factors are key determinants in disease causality and progression in neurological conditions, including multiple sclerosis (MS). Lack of exercise, poor diet, tobacco smoking, excessive alcohol intake, social determinants of health, concomitant medications, poor sleep and comorbidities can exacerbate MS pathological processes by impacting brain health and depleting neurological reserves, resulting in more rapid disease worsening. In addition to using disease-modifying therapies to alter the disease course, therapeutic strategies in MS should aim to preserve as much neurological reserve as possible by promoting the adoption of a "brain-healthy" and "metabolically-healthy" lifestyle. Here, we recommend self-regulated lifestyle modifications that have the potential to improve brain health, directly impact on disease progression and improve outcomes in people with MS. We emphasise the importance of self-management and adopting a multidisciplinary, collaborative and person-centred approach to care that encompasses the healthcare team, family members and community support groups.

Multiple sclerosis and the risk of infection: Association of British Neurologists consensus guideline.

Infection in people with multiple sclerosis (MS) is of major concern, particularly for those receiving disease-modifying therapies. This article explores the risk of infection in people with MS and provides guidance-developed by Delphi consensus by specialists involved in their management-on how to screen for, prevent and manage infection in this population.

Neuropsychological evaluation and rehabilitation in multiple sclerosis (NEuRoMS): protocol for a mixed-methods, multicentre feasibility randomised controlled trial.

BACKGROUND: Cognitive problems affect up to 70% of people with multiple sclerosis (MS), which can negatively impact mood, ability to work, and quality of life. Addressing cognitive problems is a top 10 research priority for people with MS. Our ongoing research has systematically developed a cognitive screening and management pathway (NEuRoMS) tailored for people with MS, involving a brief cognitive evaluation and rehabilitation intervention. The present study aims to assess the feasibility of delivering the pathway and will inform the design of a definitive randomised controlled trial (RCT) to investigate the clinical and cost-effectiveness of the intervention and eventually guide its clinical implementation. METHODS: The feasibility study is in three parts. Part 1 involves an observational study of those who receive screening and support for cognitive problems, using routinely collected clinical data. Part 2 is a two-arm, parallel group, multicentre, feasibility RCT with a nested fidelity evaluation. This part will evaluate the feasibility of undertaking a definitive trial comparing the NEuRoMS intervention plus usual care to usual care only, amongst people with MS with mild cognitive problems (n = 60). In part 3, semi-structured interviews will be undertaken with participants from part 2 (n = 25), clinicians (n = 9), and intervention providers (n = 3) involved in delivering the NEuRoMS cognitive screening and management pathway. MS participants will be recruited from outpatient clinics at three UK National Health Service hospitals. DISCUSSION: Timely screening and effective management of cognitive problems in MS are urgently needed due to the detrimental consequences of cognitive problems on people with MS, the healthcare system, and wider society. The NEuRoMS intervention is based on previous and extant literature and has been co-constructed with relevant stakeholders. If effective, the NEuRoMS pathway will facilitate timely identification and management of cognitive problems in people with MS. TRIAL REGISTRATION: ISRCTN11203922 . Prospectively registered on 09.02.2021.

Response to COVID-19 booster vaccinations in seronegative people with multiple sclerosis.

BACKGROUND: People with MS treated with anti-CD20 therapies and fingolimod often have attenuated responses to initial COVID-19 vaccination. However, uncertainties remain about the benefit of a 3rd (booster) COVID-19 vaccine in this group. METHODS: PwMS without a detectable IgG response following COVID-19 vaccines 1&2 were invited to participate. Participants provided a dried blood spot +/- venous blood sample 2-12 weeks following COVID-19 vaccine 3. Humoral and T cell responses to SARS-CoV-2 spike protein and nucleocapsid antigen were measured. RESULTS: Of 81 participants, 79 provided a dried blood spot sample, of whom 38 also provided a whole blood sample; 2 provided only whole blood. Anti-SARS-CoV-2-spike IgG seroconversion post-COVID-19 vaccine 3 occurred in 26/79 (33%) participants; 26/40 (65%) had positive T-cell responses. Overall, 31/40 (78%) demonstrated either humoral or cellular immune response post-COVID-19 vaccine 3. There was no association between laboratory evidence of prior COVID-19 and seroconversion following vaccine 3. CONCLUSIONS: Approximately one third of pwMS who were seronegative after initial COVID-19 vaccination seroconverted after booster (third) vaccination, supporting the use of boosters in this group. Almost 8 out of 10 had a measurable immune response following 3rd COVID-19 vaccine.

Early Reduction of MRI Activity During 6 Months of Treatment With Cladribine Tablets for Highly Active Relapsing Multiple Sclerosis: MAGNIFY-MS.

BACKGROUND AND OBJECTIVES: The onset of action for high-efficacy immunotherapies in multiple sclerosis (MS) is an important parameter. This study (MAGNIFY-MS) evaluates the onset of action of cladribine tablets by observing changes in combined unique active (CUA) MRI lesion counts during the first 6 months of treatment in patients with highly active relapsing MS. METHODS: MRI was performed at screening, baseline, and at months 1, 2, 3, and 6 after initiating treatment with cladribine tablets 3.5 mg/kg. CUA lesion counts, defined as the sum of T1 gadolinium-enhancing (Gd+) lesions and new or enlarging active T2 lesions (without T1 Gd+), were compared between postbaseline and the baseline period and standardized to the period length and the number of MRIs performed. RESULTS: Included in this analysis were 270 patients who received ≥1 dose of cladribine tablets. After treatment initiation, significant reductions in mean CUA lesion counts were observed from month 1 onward compared with the baseline period (-1.193 between month 1 and month 6, -1.500 between month 2 and month 6, and -1.692 between month 3 and month 6; all p < 0.0001). Mean T1 Gd+ lesion counts were decreased from month 2 onward compared with baseline (-0.857 at month 2, -1.355 at month 3, and -1.449 at month 6; all p < 0.0001), whereas the proportion of patients without any CUA lesions increased from 52.0% between month 1 and month 6 to 80.5% between month 3 and month 6. DISCUSSION: Findings suggest an early onset of action for cladribine tablets, with an increasing reduction in active MRI lesions over time. TRIAL REGISTRATION INFORMATION: NCT03364036; Date registered: December 06, 2017. CLASSIFICATION OF EVIDENCE: Using frequent MRI assessments of the brain over the first 6 months of the MAGNIFY-MS study (NCT03364036), we aimed to determine the onset of action of cladribine tablets 3.5 mg/kg in adult patients with highly active relapsing MS. This study provides Class IV evidence that, in such patients, treatment with cladribine tablets is associated with an early onset of action with reductions in active MRI lesion counts from month 2 (day 60) onward, with an increasing reduction in such lesions over time.

Seroconversion following COVID-19 vaccination: can we optimize protective response in CD20-treated individuals?

Although there is an ever-increasing number of disease-modifying treatments for relapsing multiple sclerosis (MS), few appear to influence coronavirus disease 2019 (COVID-19) severity. There is concern about the use of anti-CD20-depleting monoclonal antibodies, due to the apparent increased risk of severe disease following severe acute respiratory syndrome corona virus two (SARS-CoV-2) infection and inhibition of protective anti-COVID-19 vaccine responses. These antibodies are given as maintenance infusions/injections and cause persistent depletion of CD20+ B cells, notably memory B-cell populations that may be instrumental in the control of relapsing MS. However, they also continuously deplete immature and mature/naïve B cells that form the precursors for infection-protective antibody responses, thus blunting vaccine responses. Seroconversion and maintained SARS-CoV-2 neutralizing antibody levels provide protection from COVID-19. However, it is evident that poor seroconversion occurs in the majority of individuals following initial and booster COVID-19 vaccinations, based on standard 6 monthly dosing intervals. Seroconversion may be optimized in the anti-CD20-treated population by vaccinating prior to treatment onset or using extended/delayed interval dosing (3-6 month extension to dosing interval) in those established on therapy, with B-cell monitoring until (1-3%) B-cell repopulation occurs prior to vaccination. Some people will take more than a year to replete and therefore protection may depend on either the vaccine-induced T-cell responses that typically occur or may require prophylactic, or rapid post-infection therapeutic, antibody or small-molecule antiviral treatment to optimize protection against COVID-19. Further studies are warranted to demonstrate the safety and efficacy of such approaches and whether or not immunity wanes prematurely as has been observed in the other populations.

The Expression of Active CD11b Monocytes in Blood and Disease Progression in Amyotrophic Lateral Sclerosis.

Monocytes expressing the inflammation suppressing active CD11b, a beta2 integrin, may regulate neuroinflammation and modify clinical outcomes in amyotrophic lateral sclerosis (ALS). In this single site, retrospective study, peripheral blood mononuclear cells from 38 individuals living with ALS and 20 non-neurological controls (NNC) were investigated using flow cytometry to study active CD11b integrin classical (CM), intermediate (IM) and non-classical (NCM) monocytes during ALS progression. Seventeen ALS participants were sampled at the baseline (V1) and at two additional time points (V2 and V3) for longitudinal analysis. Active CD11b+ CM frequencies increased steeply between the baseline and V3 (ANOVA repeated measurement, p < 0.001), and the V2/V1 ratio negatively correlated with the disease progression rate, similar to higher frequencies of active CD11b+ NCM at the baseline (R = −0.6567; p = 0.0031 and R = 0.3862; p = 0.0168, respectively). CD11b NCM, clinical covariates and neurofilament light-chain plasma concentration at the baseline predicted shorter survival in a multivariable and univariate analysis (CD11b NCM­HR: 1.05, CI: 1.01−1.11, p = 0.013. Log rank: above median: 43 months and below median: 21.22 months; p = 0.0022). Blood samples with the highest frequencies of active CD11b+ IM and NCM contained the lowest concentrations of soluble CD11b. Our preliminary data suggest that the levels of active CD11b+ monocytes and NCM in the blood predict different clinical outcomes in ALS.