Serum 25-hydroxyvitamin D levels in multiple sclerosis patients from the north of Portugal

Increasing evidence has shown that individuals with Multiple Sclerosis (MS) have lower 25-hydroxyvitamin D [25(OH)D] levels compared to healthy controls. There is no information regarding 25(OH)D levels and MS in Portugal. Therefore the aim of the current study was to examine the levels of 25(OH)D in a group of patients with MS and in healthy matched controls, as well as the association of 25(OH)D levels with disease course, disability and severity. A group of 244 unrelated Portuguese patients, with a definitive diagnosis of MS, and 198 ethnically matched healthy controls were included in the study. A sub-group of patients with recent disease onset was included. Serum 25(OH)D was measured using an electrochemiluminescence binding assay. The mean serum level of 25(OH)D in patients with MS was 39.9±22.0 nmol/L, which was significantly lower (p<0.0001) than those in healthy controls, 55.4±23.4 nmol/L. There was a negative correlation between 25(OH)D levels and EDSS (r=-0.293, p<0.0001) and MSSS scores (r=-0.293, p<0.0001). In multiple logistic regression analysis adjusted for age, gender, disease form, EDSS, disease duration and MSSS, 25(OH)D levels were independently associated with EDSS (p=0.004) and disease duration (p=0.016), and with MSSS (p=0.001). In accordance with the majority of the literature, low serum 25(OH)D levels were associated with susceptibility and disability in MS patients from Portugal. Lower serum 25(OH)D levels were also found in patients with a recent disease onset, supporting vitamin D levels as a risk factor for MS.Andreia Bettencourt has received a PhD grant (SFRH/BD/112355/2015) from National Funds through the FCT − Fundação para a Ciência e a Tecnologia (Portuguese national funding agency for science, research and technology) in the frameworks of the UID/Multi/00215/2013 project − Unit for Multidisciplinary Research in Biomedicine − UMIB/ICBAS/UP. The study of serum 25(OH)D levels in a healthy population from the North of Portugal, included in this work, was supported by Merck S.A.info:eu-repo/semantics/publishedVersio

Serum 25-hydroxyvitamin D levels in a healthy population from the North of Portugal

Vitamin D status in human populations has become a matter of great concern, in the wake of a multitude of published works that document widespread vitamin D deficiency across Europe, even in countries with abundant sunlight. In Portugal there are no measures of 25-hydroxyvitamin D - 25(OH)D - levels in the general adult population. The purpose of this study was to measure 25(OH)D levels in a healthy population cohort and investigate the possible association with season and selected demographic and laboratory measurements. A cohort of 198 participants (18-67 years) living in the north of Portugal, Porto, conducted in July and August 2015 (summer time) and April 2016 (winter time) was studied to evaluate serum 25(OH)D levels. Sociodemographic characteristics (age, sex and body mass index) and season of the year were taken into account as possible 25(OH)D levels codeterminants. In the whole group, the mean level of serum 25(OH)D was 55.4±23.4 nmol/L, with 48% of the population presenting levels compatible with vitamin D deficiency (below 50 nmol/L). In the winter period, this value reaches 74%. No statistically significant differences were observed between genders (57.4±23.9 vs. 53.3±22.8 nmol/L, p=0.219) as well as no statistically significant correlation was found between age and 25(OH)D levels (p=0.349). As expected higher levels of 25(OH)D were observed in summer than in winter (68.2±21.5 vs. 42.2±16.9 nmol/L; p<0.0001). Serum 25(OH)D levels were significantly lower in obese compared to non-obese subjects (46.6±17.6 vs. 57.7±24.2 nmol/L, p=0.012). Vitamin D deficiency is prevalent in this area, affecting almost half of the population. Body mass index and season are predictors for lower 25-hydroxyvitamin D levels and vitamin D status. An effective strategy to prevent vitamin D deficiency and insufficiency should be envisaged and implemented in our population.info:eu-repo/semantics/publishedVersio

The vitamin D receptor gene FokI polymorphism and Multiple Sclerosis in a Northern Portuguese population

The cause of Multiple Sclerosis (MS) remains poorly understood, but it is widely believed to be an autoimmune disease occurring in genetically susceptible individuals after exposure to as-yet undefined environmental factors. One of these environmental factors is vitamin D, a well-known immune modulator. The biologically active form of vitamin D, 1,25-dihydroxyvitamin D3, has been shown to exert its immune modulatory properties through its nuclear receptor (VDR) namely by inhibiting the proliferation of Th cells. The purpose of this study was to evaluate the influence of FokI VDR polymorphism in MS development and progression.info:eu-repo/semantics/publishedVersio

People with Primary Progressive Multiple Sclerosis Have a Lower Number of Central Memory T Cells and HLA-DR+ Tregs

The importance of circulating immune cells to primary progressive multiple sclerosis (PPMS) pathophysiology is still controversial because most immunotherapies were shown to be ineffective in treating people with PPMS (pwPPMS). Yet, although controversial, data exist describing peripheral immune system alterations in pwPPMS. This study aims to investigate which alterations might be present in pwPPMS free of disease-modifying drugs (DMD) in comparison to age- and sex-matched healthy controls. A multicentric cross-sectional study was performed using 23 pwPPMS and 23 healthy controls. The phenotype of conventional CD4+ and CD8+ T cells, regulatory T cells (Tregs), B cells, natural killer (NK) T cells and NK cells was assessed. Lower numbers of central memory CD4+ and CD8+ T cells and activated HLA-DR+ Tregs were observed in pwPPMS. Regarding NK and NKT cells, pwPPMS presented higher percentages of CD56dimCD57+ NK cells expressing NKp46 and of NKT cells expressing KIR2DL2/3 and NKp30. Higher disease severity scores and an increasing time since diagnosis was correlated with lower numbers of inhibitory NK cells subsets. Our findings contribute to reinforcing the hypotheses that alterations in peripheral immune cells are present in pwPPMS and that changes in NK cell populations are the strongest correlate of disease severity

The vitamin D receptor gene FokI polymorphism and Multiple Sclerosis in a Northern Portuguese population

The cause of Multiple Sclerosis (MS) remains poorly understood, but it is widely believed to be an autoimmune disease occurring in genetically susceptible individuals after exposure to as-yet undefined environmental factors. One of these environmental factors is vitamin D, a well-known immune modulator. The biologically active form of vitamin D, 1,25-dihydroxyvitamin D3, has been shown to exert its immune modulatory properties through its nuclear receptor (VDR) namely by inhibiting the proliferation of Th cells. The purpose of this study was to evaluate the influence of FokI VDR polymorphism in MS development and progression.info:eu-repo/semantics/publishedVersio

Immunogenetic predisposing factors for mesial temporal lobe epilepsy with hippocampal sclerosis

Purpose: Neuroinflammation appears as an important epileptogenic mechanism. Experimental and clinical studies have demonstrated an upregulation of pro-inflammatory cytokines such as IL-1β and TNF-α, in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Expression of these cytokines can be modulated by polymorphisms such as rs16944 and rs1800629, respectively, both of which have been associated with febrile seizures (FS) and MTLE-HS development. The human leukocyte antigen (HLA) system has also been implicated in diverse epileptic entities, suggesting a variable role of this system in epilepsy. Our aim was to analyse the association between immunogenetic factors and MTLE-HS development. For that rs16944 (-511 T>C, IL-1β), rs1800629 (-308 G>A, TNF-α) polymorphisms and HLA-DRB1 locus were genotyped in a Portuguese Population. Methods: We studied 196 MTLE-HS patients (108 females, 88 males, 44.7 ± 12.0 years, age of onset = 13.6 ± 10.3 years, 104 with FS antecedents) and 282 healthy controls in a case–control study. Results: The frequency of rs16944 TT genotype was higher in MTLE-HS patients compared to controls (14.9% in MTLE-HS vs. 7.7% in controls, p = 0.021, OR [95% CI] = 2.20 [1.13–4.30]). This association was independent of FS antecedents. No association was observed between rs1800629 genotypes or HLA-DRB1 alleles and MTLE-HS susceptibility. Also, no correlation was observed between the studied polymorphisms and disease age of onset. Conclusion: The rs16944 TT genotype is associated with MTLE-HS development what may be explained by the higher IL-1β levels produced by this genotype. High IL-1β levels may have neurotoxic effects or imbalance neurotransmission leading to seizures.This research was partially funded by a BICE Tecnifar Grant.info:eu-repo/semantics/publishedVersio

People with primary progressive multiple sclerosis have a lower number of central memory T cells and HLA-DR+ Tregs

The importance of circulating immune cells to primary progressive multiple sclerosis (PPMS) pathophysiology is still controversial because most immunotherapies were shown to be ineffective in treating people with PPMS (pwPPMS). Yet, although controversial, data exist describing peripheral immune system alterations in pwPPMS. This study aims to investigate which alterations might be present in pwPPMS free of disease-modifying drugs (DMD) in comparison to age- and sex-matched healthy controls. A multicentric cross-sectional study was performed using 23 pwPPMS and 23 healthy controls. The phenotype of conventional CD4+ and CD8+ T cells, regulatory T cells (Tregs), B cells, natural killer (NK) T cells and NK cells was assessed. Lower numbers of central memory CD4+ and CD8+ T cells and activated HLA-DR+ Tregs were observed in pwPPMS. Regarding NK and NKT cells, pwPPMS presented higher percentages of CD56dimCD57+ NK cells expressing NKp46 and of NKT cells expressing KIR2DL2/3 and NKp30. Higher disease severity scores and an increasing time since diagnosis was correlated with lower numbers of inhibitory NK cells subsets. Our findings contribute to reinforcing the hypotheses that alterations in peripheral immune cells are present in pwPPMS and that changes in NK cell populations are the strongest correlate of disease severity.This work has been funded by a research grant from the Academic Clinical Center of the Hospital of Braga; by national funds through the Foundation for Science and Technology (FCT) (UIDB/50026/2020 and UIDP/50026/2020); and by the project NORTE-01-0145-FEDER-000039, supported by the Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). J.C.-G. has been supported by FCT PhD grants (PD/BD/137433/2018 and COVID/BD/152629/2022). C.S. has been supported by an FCT PhD grant (PD/BDE/142976/2018)

HLA and age of onset in myasthenia gravis

The aetiology of MG is unknown, but both genetic and environmental factors are important. Over the years association of MG with Human Leucocyte Antigens (HLA) has been described in different populations. We investigated a possible association between HLA-DRB1 alleles and age of onset in MG. One hundred and fourteen MG patients (82 females) and 282 control individuals (CP) were studied. Patients were classified according to the age of onset (early-onset <50, n = 74 and late-onset ≥ 50, n = 20). Patients with thymoma (n = 20) were analyzed separately. HLA-DRB1 and HLA-B*08 genotyping was performed using PCR-SSP methodology. HLA-DRB1*03 allele was overrepresented in the global MG. When the early-onset subgroup was considered, this association became even stronger. Regarding the late-onset subgroup, the frequency of HLA-DRB1*01 allele was higher than in the CP. For the thymoma subgroup, the HLA-DRB1*10 allele frequency was significantly higher when compared to the CP. These results have shown a strong association of HLA-DRB1*03 with MG, especially for EOMG also in our population. HLA-DRB1*01 was associated to LOMG suggesting that is a susceptibility factor for this subgroup of the disease. This study confirms a different genetic background of MG subgroups regarding age of onset.info:eu-repo/semantics/publishedVersio

HLA and age of onset in myasthenia gravis

The aetiology of MG is unknown, but both genetic and environmental factors are important. Over the years association of MG with Human Leucocyte Antigens (HLA) has been described in different populations. We investigated a possible association between HLA-DRB1 alleles and age of onset in MG. One hundred and fourteen MG patients (82 females) and 282 control individuals (CP) were studied. Patients were classified according to the age of onset (early-onset <50, n = 74 and late-onset ≥ 50, n = 20). Patients with thymoma (n = 20) were analyzed separately. HLA-DRB1 and HLA-B*08 genotyping was performed using PCR-SSP methodology. HLA-DRB1*03 allele was overrepresented in the global MG. When the early-onset subgroup was considered, this association became even stronger. Regarding the late-onset subgroup, the frequency of HLA-DRB1*01 allele was higher than in the CP. For the thymoma subgroup, the HLA-DRB1*10 allele frequency was significantly higher when compared to the CP. These results have shown a strong association of HLA-DRB1*03 with MG, especially for EOMG also in our population. HLA-DRB1*01 was associated to LOMG suggesting that is a susceptibility factor for this subgroup of the disease. This study confirms a different genetic background of MG subgroups regarding age of onset.info:eu-repo/semantics/publishedVersio