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1.
Immunology ; 171(4): 618-633, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38243672

RESUMEN

Oligodendrocyte progenitor cells (OPCs) were regarded for years solely for their regenerative role; however, their immune-modulatory roles have gained much attention recently, particularly in the context of multiple sclerosis (MS). Despite extensive studies on OPCs, there are limited data elucidating the interactions between their intrinsic regenerative and immune functions, as well as their relationship with the inflamed central nervous system (CNS) environment, a key factor in MS pathology. We examined the effects of pro-inflammatory cytokines, represented by interferon (IFN)-γ and tumour necrosis factor (TNF)-α, as well as anti-inflammatory cytokines, represented by interleukin (IL)-4 and IL-10, on OPC differentiation and immune characteristics. Using primary cultures, enzyme-linked immunosorbent assay and immunofluorescence stainings, we assessed differentiation capacity, phagocytic activity, major histocompatibility complex (MHC)-II expression, and cytokine secretion. We observed that the anti-inflammatory milieu (IL4 and IL10) reduced both OPC differentiation and immune functions. Conversely, exposure to TNF-α led to intact differentiation, increased phagocytic activity, high levels of MHC-II expression, and cytokines secretion. Those effects were attributed to signalling via TNF-receptor-2 and counteracted the detrimental effects of IFN-γ on OPC differentiation. Our findings suggest that a pro-regenerative, permissive inflammatory environment is needed for OPCs to execute both regenerative and immune-modulatory functions.


Asunto(s)
Esclerosis Múltiple , Células Precursoras de Oligodendrocitos , Humanos , Células Precursoras de Oligodendrocitos/metabolismo , Citocinas/metabolismo , Diferenciación Celular , Esclerosis Múltiple/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Inmunidad , Antiinflamatorios/farmacología , Oligodendroglía
2.
Glia ; 71(12): 2815-2831, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37610097

RESUMEN

Remyelination failure is considered a major obstacle in treating chronic-progressive multiple sclerosis (MS). Studies have shown blockage in the differentiation of resident oligodendrocyte progenitor cells (OPC) into myelin-forming cells, suggesting that pushing OPC into a differentiation program might be sufficient to overcome remyelination failure. Others stressed the need for a permissive environment to allow proper activation, migration, and differentiation of OPC. PD0325901, a MAPK/ERK inhibitor, was previously shown to induce OPC differentiation, non-specific immunosuppression, and a significant therapeutic effect in acute demyelinating MS models. We examined PD0325901 effects in the chronically inflamed central nervous system. Treatment with PD0325901 induced OPC differentiation into mature oligodendrocytes with high morphological complexity. However, treatment of Biozzi mice with chronic-progressive experimental autoimmune encephalomyelitis with PD0325901 showed no clinical improvement in comparison to the control group, no reduction in demyelination, nor induction of OPC migration into foci of demyelination. PD0325901 induced a direct general immunosuppressive effect on various cell populations, leading to a diminished phagocytic capability of microglia and less activation of lymph-node cells. It also significantly impaired the immune-modulatory functions of OPC. Our findings suggest OPC regenerative function depends on a permissive environment, which may include pro-regenerative inflammatory elements. Furthermore, they indicate that maintaining a delicate balance between the pro-myelinating and immune functions of OPC is of importance. Thus, the highly complex mission of creating a pro-regenerative environment depends upon an appropriate immune response controlled in time, place, and intensity. We suggest the need to employ a multi-systematic therapeutic approach, which cannot be achieved through a single molecule-based therapy.

3.
Ann Neurol ; 91(6): 796-800, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35243687

RESUMEN

The introduction of a third-dose vaccination along with new variants of concern raises questions regarding serology and T-cell responses in patients with multiple sclerosis (pwMS) treated with B-cell depletion who develop attenuated humoral response to vaccines. The aim of this study was to longitudinally evaluate humoral and cellular response to SARS-CoV-2 mRNA vaccine in ocrelizumab-treated pwMS before and following a third vaccine dose. Following the third vaccine dose, patients who are low or nonresponders following initial vaccination did not increase antibody titers. In healthy controls and ocrelizumab-treated pwMS, cellular response decreased 6 months after initial vaccination and increased significantly after the third dose. ANN NEUROL 2022;91:796-800.


Asunto(s)
COVID-19 , Esclerosis Múltiple , Anticuerpos Monoclonales Humanizados , Anticuerpos Antivirales , Vacunas contra la COVID-19/uso terapéutico , Humanos , Inmunidad , Esclerosis Múltiple/tratamiento farmacológico , SARS-CoV-2 , Vacunas Sintéticas , Vacunas de ARNm
4.
Neurol Sci ; 44(11): 3989-3996, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37358691

RESUMEN

BACKGROUND: Pregnancy has been observed to reduce the frequency of relapses in Multiple Sclerosis (MS) patients, but the relapse risk tends to increase during the early post-partum period. Increased pre- and post-partum disease activity may predict a poor long-term prognosis. This study aimed to evaluate the correlation between magnetic resonance imaging (MRI) activity during the year before pregnancy and long-term clinically meaningful worsening in Expanded Disability Status Scale (EDSS). METHODS: This observational, retrospective, case-control study included 141 pregnancies in 99 females with MS. Statistical analyses were used to evaluate the correlation between MRI activity during the year pre-pregnancy and post-partum clinical worsening during a 5-year follow-up. Clustered logistic regression was used to investigate the predictors of 5-year clinically meaningful worsening in EDSS (lt-EDSS). RESULTS: We found a significant correlation between an active MRI pre-pregnancy and lt-EDSS (p = 0.0006). EDSS pre-pregnancy and lt-EDSS were also significantly correlated (p = 0.043). Using a multivariate model, we predicted which females would not experience long-term clinical deterioration by a stable MRI pre-pregnancy (92.7% specificity; p = 0.004). CONCLUSIONS: An active MRI pre-conception is a strong predictor of lt-EDSS and a higher annual relapse rate during the follow-up period, regardless of whether the female had clinical evidence of disease activity prior to conception and delivery. Optimizing disease control and achieving imaging stability prior to conception may reduce the risk of long-term clinical deterioration.

5.
Glia ; 70(6): 1191-1209, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35266197

RESUMEN

Oligodendrocyte progenitor cells (OPCs) are responsible for remyelination in the central nervous system (CNS) in health and disease. For patients with multiple sclerosis (MS), remyelination is not always successful, and the mechanisms differentiating successful from failed remyelination are not well-known. Growing evidence suggests an immune role for OPCs, in addition to their regenerative role; however, it is not clear if this helps or hinders the regenerative process. We studied the effect of cerebrospinal fluid (CSF) from relapsing MS (rMS) and progressive MS (pMS) patients on primary OPC differentiation and immune gene expression and function. We observed that CSF from either rMS or pMS patients has a differential effect on the ability of mice OPCs to differentiate into mature oligodendrocytes and to express immune functions. CSF of pMS patients impaired differentiation into mature oligodendrocytes. In addition, it led to decreased major histocompatibility complex class (MHC)-II expression, tumor necrosis factor (TNF)-α secretion, nuclear factor kappa-B (NFκB) activation, and less activation and proliferation of T cells. Our findings suggest that OPCs are not only responsible for remyelination, but they may also play an active role as innate immune cells in the CNS.


Asunto(s)
Esclerosis Múltiple , Células Precursoras de Oligodendrocitos , Remielinización , Animales , Diferenciación Celular/fisiología , Humanos , Inmunidad , Ratones , Esclerosis Múltiple/patología , Vaina de Mielina/metabolismo , Células Precursoras de Oligodendrocitos/metabolismo , Oligodendroglía/metabolismo , Remielinización/fisiología
6.
Int J Mol Sci ; 23(13)2022 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-35806122

RESUMEN

Neuromyelitis optica (NMO) is a rare disease usually presenting with bilateral or unilateral optic neuritis with simultaneous or sequential transverse myelitis. Autoantibodies directed against aquaporin-4 (AQP4-IgG) are found in most patients. They are believed to cross the blood−brain barrier, target astrocytes, activate complement, and eventually lead to astrocyte destruction, demyelination, and axonal damage. However, it is still not clear what the primary pathological event is. We hypothesize that the interaction of AQP4-IgG and astrocytes leads to DNA damage and apoptosis. We studied the effect of sera from seropositive NMO patients and healthy controls (HCs) on astrocytes' immune gene expression and viability. We found that sera from seropositive NMO patients led to higher expression of apoptosis-related genes, including BH3-interacting domain death agonist (BID), which is the most significant differentiating gene (p < 0.0001), and triggered more apoptosis in astrocytes compared to sera from HCs. Furthermore, NMO sera increased DNA damage and led to a higher expression of immunological genes that interact with BID (TLR4 and NOD-1). Our findings suggest that sera of seropositive NMO patients might cause astrocytic DNA damage and apoptosis. It may be one of the mechanisms implicated in the primary pathological event in NMO and provide new avenues for therapeutic intervention.


Asunto(s)
Neuromielitis Óptica , Apoptosis , Acuaporina 4/metabolismo , Astrocitos/metabolismo , Autoanticuerpos , Humanos , Inmunoglobulina G
7.
Mult Scler ; 27(14): 2232-2239, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-33783260

RESUMEN

BACKGROUND: There are fewer multiple sclerosis (MS) relapses during pregnancy, although relapse risk increases in the early post-partum period, as has been predicted by pre-pregnancy or pregnancy disease activity in some studies. OBJECTIVE: The aim of this study was to evaluate the correlation between magnetic resonance imaging (MRI) changes in the year before pregnancy and the relapse rate in the year post-partum. METHODS: An observational retrospective case-control study included 172 pregnancies in 118 females with MS. Statistical analyses were used to evaluate the correlation between MRI and post-partum relapses. Clustered logistic regression was used to investigate the predictors of early post-partum relapses. RESULTS: We found a significant correlation for an active-MRI pre-pregnancy and relapses in the first 3 months post-partum (p < 0.001). Expanded Disability Status Scale (EDSS) pre-pregnancy and relapses in the first 3 months post-partum were also significantly correlated (p = 0.009). Using a multivariate model, we predicted which women will not experience post-partum relapse by EDSS and by an active-MRI pre-pregnancy (96.7% specificity; p < 0.001). CONCLUSION: An active-MRI pre-pregnancy is a strong and sensitive predictor of early post-partum relapse, regardless of whether the woman had clinical evidence of disease activity prior to conception and delivery. This finding could provide clinicians with a strategy to minimize post-partum relapse risk in women with MS planning pregnancy.


Asunto(s)
Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Encéfalo/diagnóstico por imagen , Estudios de Casos y Controles , Femenino , Humanos , Imagen por Resonancia Magnética , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Periodo Posparto , Embarazo , Recurrencia , Estudios Retrospectivos
8.
J Neurol Sci ; 457: 122866, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38242048

RESUMEN

BACKGROUND: Thyroid hormones play a critical role in both neuronal and glial cell functions. Multiple sclerosis (MS) has increased co-occurrence with autoimmune thyroid diseases, and recent studies have suggested a potential link between neuromyelitis optica spectrum disorder (NMOSD) and thyroid hormones. However, no previous studies have examined the relationship between thyroid hormones and myelin oligodendrocyte glycoprotein-associated demyelination (MOGAD). METHODS: We investigated the role of thyroid hormones in central nervous system (CNS) autoimmune demyelinating diseases in 26 MOGAD patients, 52 NMOSD patients, 167 patients with MS, and 16 patients with other noninflammatory neurological disorders. Thyroid hormone levels and clinical data (Expanded Disability Status Scale [EDSS]) were analyzed. Volumetric brain information was determined in brain magnetic resonance imaging (MRI) using the MDbrain platform. RESULTS: MOGAD patients had significantly higher levels of free triiodothyronine (FT3) compared to NMOSD patients. No correlation was found between FT3 levels and disease severity or brain volume. Thyroid-stimulating hormone (TSH) levels did not differ significantly between the groups, but in NMOSD patients, higher TSH levels were associated with lower disability scores and increased brain volume. No significant differences in free thyroxine (FT4) levels were observed between the different groups, however, FT4 levels were significantly higher in relapsing versus monophasic MOGAD patients and increased FT4 levels were associated with a higher EDSS and lower brain volume in NMOSD patients. CONCLUSION: Our findings highlight the potential involvement of thyroid hormones specifically in MOGAD patients and other demyelinating CNS disorders. Understanding the role of thyroid hormones in relapsing vs monophasic MOGAD patients and in comparison to other demyelinating disorder could lead to the development of therapeutic interventions. Further studies are needed to explore the precise mechanisms and potential interventions targeting the thyroid axis as a treatment strategy.


Asunto(s)
Enfermedad de Hashimoto , Esclerosis Múltiple , Neuromielitis Óptica , Humanos , Glicoproteína Mielina-Oligodendrócito , Hormonas Tiroideas , Enfermedad de Hashimoto/diagnóstico por imagen , Neuromielitis Óptica/complicaciones , Neuromielitis Óptica/diagnóstico por imagen , Tirotropina , Autoanticuerpos , Acuaporina 4
9.
J Neuroimmunol ; 391: 578351, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38703720

RESUMEN

Myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) is a demyelinating central nervous system disorder. We aimed to uncover immune pathways altered in MOGAD to predict disease progression. Using nanostring nCounter technology, we analyzed immune gene expression in PBMCs from MOGAD patients and compare it with healthy controls (HCs). We found 35 genes that distinguished MOGAD patients and HCs. We then validated those results in a larger cohort including MS and NMOSD patients. Expressions of HLA-DRA was significantly lower in MOGAD patients. This reduction in HLA-DRA, correlated with a monophasic disease course and greater brain volume, enhancing our ability to predict MOGAD progression.


Asunto(s)
Glicoproteína Mielina-Oligodendrócito , Humanos , Masculino , Femenino , Glicoproteína Mielina-Oligodendrócito/inmunología , Glicoproteína Mielina-Oligodendrócito/toxicidad , Adulto , Persona de Mediana Edad , Enfermedades Autoinmunes Desmielinizantes SNC/inmunología , Neuromielitis Óptica/inmunología , Neuromielitis Óptica/genética , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Estudios de Cohortes , Esclerosis Múltiple/inmunología
10.
J Neuroimmunol ; 388: 578289, 2024 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-38301597

RESUMEN

Co-inhibitory receptors (CIR)s regulate T cell-mediated immune responses and growing evidence links co-inhibitory receptors to the progression of neuroimmunological diseases. We studied the expression levels of CIRs: TIM-3, TIGIT, PD-1 and LAG-3 in the peripheral blood mononuclear cells (PBMCs) of 30 patients with Neuromyelitis optica spectrum disorder (NMOSD), 11 Multiple sclerosis (MS) patients and 31 Healthy controls (HC). We found that the mRNA expression levels of TIM-3 were significantly increased in NMOSD compared with HC, and increased LAG-3 surface protein expression was also observed on T-cells of NMOSD patients. Moreover, we observed a negative correlation between LAG-3 expression and disease severity in NMOSD. Our findings suggest a protective effect of LAG-3 in the setting of NMOSD, and that the differential expression of CIRs observed in this study may play a role in the pathological process of NMOSD.


Asunto(s)
Esclerosis Múltiple , Neuromielitis Óptica , Humanos , Receptor 2 Celular del Virus de la Hepatitis A , Leucocitos Mononucleares/metabolismo , Gravedad del Paciente , Receptores Inmunológicos/metabolismo
11.
J Neurol ; 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38809270

RESUMEN

INTRODUCTION: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified demyelinating disorder with a diverse clinical spectrum. Diagnosing MOGAD traditionally relies on clinical judgment, highlighting the necessity for precise diagnostic criteria. Banwell et al. proposed criteria, aiming to refine the diagnostic spectrum. This study evaluates these criteria in a real-life cohort, comparing their performance with clinical judgment and describe the cohort of MOGAD patients. METHODS: This retrospective study, conducted at Hadassah Medical Center, included 88 patients with MOG-IgG antibodies. Patients with a positive or borderline MOG-IgG antibodies by cell-based assay were included. Demographics, clinical and MRI data were recorded. Cases were divided into definite MOGAD and Non-MOGAD groups as determined by the treating physician. We assessed the sensitivity and specificity of the new criteria in comparison to treating physicians' evaluations. Additionally, we examined clinical differences between the MOGAD and Non-MOGAD groups. RESULTS: We observed a strong concordance (98%) between the new MOGAD criteria and treating physicians' diagnoses. Clinical disparities between MOGAD and Non-MOGAD groups included lower EDSS scores, normal MRI scans, preserved brain volume, negative OCB results, and distinct relapse patterns. Also, compared to relapsing patients, monophasic MOGAD patients have greater brain volume and a lower age at onset. CONCLUSION: The study demonstrates robust accuracy of new MOGAD criteria, emphasizing their potential to enhance diagnostic precision. Treatment response integration into the MOGAD diagnosis is crucial, as it could aid in distinguishing MOGAD from other demyelinating disorders. Distinct clinical profiles highlight the importance of informed decisions in managing MOGAD and similar disorders.

12.
J Neuroimmunol ; 370: 577925, 2022 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-35810527

RESUMEN

To date, there are no accepted soluble markers for disease activity and progression of neuromyelitis optica spectrum disorder (NMOSD). We aimed to evaluate longitudinal interleukin (IL)-6 levels in sera of NMOSD patients in correlation with disease activity and brain volume. We analyzed IL-6 serum levels of 26 NMOSD patients during relapse and remission. Significantly increased IL-6 levels were detected in patients with NMOSD during relapse. Furthermore, increased IL-6 levels correlated with relapse severity and brain atrophy. Our findings suggest that IL-6 serum level could serve as a biomarker for disease activity in NMOSD.


Asunto(s)
Interleucina-6/análisis , Neuromielitis Óptica , Biomarcadores , Humanos , Neuromielitis Óptica/diagnóstico , Recurrencia
13.
Mult Scler Relat Disord ; 63: 103863, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35667316

RESUMEN

BACKGROUND: Multiple sclerosis (MS) patients receive immunomodulatory treatments which can influence their ability to maintain vaccine specific serological response overtime. MS patients treated with cladribine tablets developed a positive serology response following two doses of mRNA COVID-19 vaccine. However, there is only limited data regarding the effect of cladribine tablets on long-term humoral response after the second and the third booster. METHODS: Serology response to SARS-CoV-2 was tested in healthy controls (HCs) and MS patients treated with cladribine tablets 6 and 9-12 months after the second dose, and 1 and 3-6 months following the third booster-dose of the BTN162b2 mRNA vaccine. RESULTS: Thirty-five out of 36 MS patients treated with cladribine tablets and 100% (46/46) of HCs had a positive serology response up to 10 months after the second vaccine dose. In addition, all cladribine tablets -treated MS patients (22/22) and HCs (24/24) had a positive robust serology response following the third vaccine with a positive humoral response sustain up to 6 months. One month after the third vaccine dose IgG levels were significantly lower in patients treated with cladribine tablets compared to HCs (15,598+11,313 vs 26,394+11,335, p<0.01). Six-month post second vaccine and 3-6 months post third vaccine there was no difference in IgG levels between the groups (1088.0 ± 1072.0 vs 1153.0 ± 997.1, p = 0.79; 5234+4097 vs 11,198+14,679, p = 0.4). CONCLUSION AND RELEVANCE: MS patients treated with cladribine tablets have sustained positive vaccine specific serology response following the second and third SARS-CoV-2 vaccine dose.


Asunto(s)
COVID-19 , Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19 , Cladribina/efectos adversos , Humanos , Inmunoglobulina G/uso terapéutico , Inmunosupresores/efectos adversos , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , SARS-CoV-2 , Comprimidos , Vacunas Sintéticas , Vacunas de ARNm
14.
Front Neurol ; 13: 867190, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35401390

RESUMEN

Background: Myelin oligodendrocyte glycoprotein antibody disorders (MOGAD) have evolved as a distinct group of inflammatory, demyelinating diseases of the CNS. MOGAD can present with a monophasic or relapsing disease course with distinct clinical manifestations.However, data on the disease course and disability outcomes of these patients are scarce. We aim to compare brain volumetric changes for MOGAD patients with different disease phenotypes and HCs. Methods: Brain magnetic resonance imaging (MRI) scans and clinical data were obtained for 22 MOGAD patients and 22 HCs. Volumetric brain information was determined using volBrain and MDbrain platforms. Results: We found decreased brain volume in MOGAD patients compared to HCs, as identified in volume of total brain, gray matter, white matter and deep gray matter (DGM) structures. In addition, we found significantly different volumetric changes between patients with relapsing and monophasic disease course, with significantly decreased volume of total brain and DGM, cerebellum and hippocampus in relapsing patients during the first year of diagnosis. A significant negative correlation was found between EDSS and volume of thalamus. Conclusions: Brain MRI analyses revealed volumetric differences between MOGAD patients and HCs, and between patients with different disease phenotypes. Decreased gray matter volume during the first year of diagnosis, especially in the cerebrum and hippocampus of MOGAD patients was associated with relapsing disease course.

15.
Mult Scler Relat Disord ; 57: 103343, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35158452

RESUMEN

BACKGROUND: multiple sclerosis (MS) patients are treated with immunomodulatory treatments that can influence their ability to develop a protective antibody response to the SARS-CoV-2 vaccine. Vaccine efficacy is important for treatment decision and for patients' reassurance. The main objective is to assess antibody response to SARS-CoV-2 vaccine in MS patients treated with cladribine. METHODS: Serology response was tested in 97 participants, 67 MS patients and 30 healthy controls (HCs), using two independent methods, 2-3 weeks following the second dose of the BNT162b2 vaccine. RESULTS: HCs (n = 30) and MS patients treated with cladribine (n = 32) had 100% positive serology response against the SARS-CoV-2 spike protein following the second vaccine dose (mean S1/S2-IgG and RBD-IgG:284.5 ± 104.9, 13,041±9411 AU/mL and 226.3 ± 121.4, 10,554±11,405 AU/mL respectively). Comparable findings were observed for untreated MS patients, and interferon beta-1a-treated MS patients (mean S1/S2-IgG: 282.1 ± 100.1, 276.9 ± 94.31 AU/mL respectively). No correlation was found between lymphocyte counts, treatment duration, or time between cladribine dose and vaccination, and serology response or antibody titers. CONCLUSION AND RELEVANCE: Cladribine treated MS patients are able to produce antibodies to the SARS-CoV-2 mRNA vaccine. In the era of the COVID-19 pandemic, it is reassuring and important for both patients and physicians and will allow to develop consensus guidelines.


Asunto(s)
COVID-19 , Esclerosis Múltiple , Anticuerpos Antivirales , Vacuna BNT162 , Vacunas contra la COVID-19 , Cladribina , Humanos , Pandemias , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Vacunas Sintéticas , Vacunas de ARNm
16.
JAMA Neurol ; 78(12): 1510-1514, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34554197

RESUMEN

Importance: B-cell-depleting therapies may affect the development of a protective immune response following vaccination. Understanding the ability to develop vaccine-specific immunity to COVID-19 in patients with multiple sclerosis (MS) treated with B-cell-depleting therapy is of importance for clinical decisions. Objective: To assess SARS-CoV-2 vaccine-specific humoral and cellular responses in patients treated with ocrelizumab compared with healthy controls. Design, Setting, and Participants: This single-center study performed at Hadassah Medical Center in Jerusalem, Israel, included patients with MS treated with ocrelizumab, healthy controls, and untreated patients with MS. Vaccination occurred between December 2020 and April 2021. Participants donated blood 2 to 4 and 2 to 8 weeks after the second vaccine dose for antibody and T-cell assessments, respectively. Exposures: All participants received 2 doses of BNT162b2 vaccine (Pfizer/BioNTech) and completed the study. Main Outcomes and Measures: Proportion of patients treated with ocrelizumab with SARS-CoV-2-specific serology and/or T-cell responses following vaccination. All participants underwent SARS-CoV-2 antibody testing; 29 patients treated with ocrelizumab and 15 healthy controls had evaluation of SARS-CoV-2-specific T-cell responses. Results: Of 112 participants, 49 (43.8%) had MS and were treated with ocrelizumab (33 [67.3%] female; mean [SD] age, 47.9 [13.3] years), 23 (20.5%) had MS and were not treated with disease-modifying therapies (18 [78.3%] female; mean [SD] age, 49 [13.4] years), and 40 (35.7%) were healthy controls (25 [62.5%] female; mean [SD] age, 45.3 [16] years). Twenty-six of 29 patients (89.7%) treated with ocrelizumab and 15 of 15 healthy controls (100%) had SARS-CoV-2-specific T cells following vaccination at similar levels (mean [SD], 15.4 [7.6] and 14.3 [6.3] spot-forming cells, respectively). Mean antibody titers and positive serology rate were lower in the group of patients treated with ocrelizumab (mean [SD] antibody titers and positive serology rate, 26.2 [49.2] and 376.5 [907.6] AU/mL; 10 of 40 [25%] and 20 of 49 [40.8%] for S1/S2 and receptor-binding domain, respectively) compared with healthy controls (mean [SD] antibody titers and positive serology rate, 283 [100] and 12 712 [9114] AU/mL; 100% S1/S2 and receptor-binding domain) and untreated patients (mean [SD] antibody titers and positive serology rate, 288.3 [113.8] and 10 877 [9476] AU/mL; 100% S1/S2 and receptor-binding domain), with positive association to time from ocrelizumab infusion (S1/S2: r = 0.7, P < .001; receptor-binding domain: r = 0.4, P = .04). Conclusion and Relevance: In this study, patients with MS who were treated with ocrelizumab generated comparable SARS-CoV-2-specific T-cell responses with healthy controls and had lower antibody response following vaccination. Given the potential role of T cells in protection from severe disease, this is reassuring and will help physicians develop consensus guidelines regarding MS treatment in the era of the COVID-19 pandemic.


Asunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Vacunas contra la COVID-19/inmunología , Inmunidad Humoral/inmunología , Factores Inmunológicos/efectos adversos , Esclerosis Múltiple/inmunología , Linfocitos T/inmunología , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Vacuna BNT162/inmunología , COVID-19/inmunología , COVID-19/prevención & control , Femenino , Humanos , Factores Inmunológicos/uso terapéutico , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/tratamiento farmacológico
17.
J Neuroimmunol ; 339: 577120, 2020 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-31790982

RESUMEN

Our knowledge about genetic factors that drive the worsening of neuromyelitis optica (NMO) is limited. Herein, we analyzed the macrophage migration inhibitory factor (MIF) -173G/C functional polymorphism in NMO patients and controls. Our data reveal that the frequency of the high-expression MIF genotypes (CC/GC) did not differ between the two groups. However, frequency of this genotypes was elevated in patients diagnosed with both optic neuritis and myelitis compared with patients that were diagnosed with only one symptom. Furthermore, patients carrying the CC/CG genotypes had significantly higher disability score. We conclude that MIF is associated with NMO severity rather than susceptibility.


Asunto(s)
Oxidorreductasas Intramoleculares/genética , Factores Inhibidores de la Migración de Macrófagos/genética , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/genética , Polimorfismo de Nucleótido Simple/genética , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
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