Rare MEFV variants are not associated with risk to develop multiple sclerosis and severity of disease

2013 ◽  
Vol 19 (9) ◽  
pp. 1132-1136 ◽  
Author(s):  
Ine Pauwels ◽  
Leentje Cosemans ◽  
Steven Boonen ◽  
Bénédicte Dubois ◽  
An Goris
Keyword(s):  
Multiple Sclerosis ◽  
Side Effects ◽  
Disease Severity ◽  
Rare Variants ◽  
Mefv Gene ◽  
P Value ◽  
Inflammatory Disorder ◽  
First Choice ◽  
Mediterranean Fever ◽  
Systemic Side Effects

Background: Recent studies suggest an association between rare variants in Mediterranean fever (MEFV), the gene underlying the auto-inflammatory disorder Familial Mediterranean Fever (FMF), the risk to develop multiple sclerosis (MS) and severity of MS. Objective: The objective of this study is to investigate these findings in a Belgian MS population and to test for association with additional clinical parameters such as treatment response. Methods: MEFV was sequenced in a cohort of MS patients ( N=94) suffering from auto-inflammatory symptoms, systemic side-effects upon interferon-beta (IFN-β) treatment, or patients in whom glatiramer acetate was started as first choice due to severe fatigue. Five rare non-synonymous variants were detected in this cohort and subsequently genotyped in 915 MS patients and 763 healthy controls. Results: We observed no association between these alleles and susceptibility to MS ( p-value=0.99) or disease severity ( p-value=0.78). However, we did observe a correlation between carrying an MEFV variant and the development of systemic side-effects upon IFN-β treatment ( p-value=0.022). Conclusion: In contrast to recent smaller studies, we did not find an association between carrying a rare variant in the MEFV gene and the risk to develop MS or disease severity. However, carrying rare variants in MEFV was associated with the development of severe systemic side-effects upon IFN-β treatment.

Familial Mediterranean fever-associated mutation pyrin E148Q as a potential risk factor for multiple sclerosis

2012 ◽  
Vol 18 (9) ◽  
pp. 1229-1238 ◽  
Author(s):  
T Kümpfel ◽  
L-A Gerdes ◽  
T Wacker ◽  
A Blaschek ◽  
J Havla ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Risk Factor ◽  
Familial Mediterranean Fever ◽  
Mefv Gene ◽  
German Population ◽  
Gene Group ◽  
Mefv Mutations ◽  
Mediterranean Fever ◽  
Group 2 ◽  
Group 1

Background: Familial Mediterranean fever (FMF) is an inherited autoinflammatory disease caused by mutations in the MEFV gene and characterized by recurrent febrile polyserositis. A possible association of FMF and multiple sclerosis (MS) has been suggested in cohorts from Turkey and Israel. Objective: The objective of this study was to investigate the prevalence of MEFV mutations in subjects with MS and in controls in Germany. Methods: One-hundred and fifty seven MS patients with at least one symptom or without symptoms suggestive of FMF from our outpatient clinic were investigated for mutations in exons 2, 3, and 10 of the MEFV gene (group 1). 260 independent MS patients (group 2) and 400 unrelated Caucasian controls (group 3) were screened selectively for the low-penetrance pyrin mutations E148Q and K695R Results: In group 1, 19 MS patients (12.1%) tested positive for a mutation in the MEFV gene, mainly the E148Q ( n=7) substitution. Fifteen of the 19 mutation-positive individuals reported at least one symptom suggestive of FMF. In three cases, we could identify additional family members with MS. In these pedigrees, the E148Q exchange co-segregated with MS ( p=0.026). Frequencies of the pyrin E148Q and K695R mutations were not statistically different between MS group 2 and controls but they occurred with a surprisingly high frequency in the German population. Conclusion: The MEFV gene appears to be another immunologically relevant gene locus which contributes to MS susceptibility. In particular, the pyrin E148Q mutation, which co-segregated with disease in three MS families, is a promising candidate risk factor for MS that should be further explored in larger studies.

scholarly journals Time of interferon-β 1a injection and duration of treatment affect clinical side effects and acute changes of plasma hormone and cytokine levels in multiple sclerosis patients

2007 ◽  
Vol 13 (9) ◽  
pp. 1138-1145 ◽  
Author(s):  
T. Kümpfel ◽  
M. Schwan ◽  
Th. Pollmächer ◽  
A. Yassouridis ◽  
M. Uhr ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Side Effects ◽  
Time Course ◽  
Group A ◽  
Systemic Side Effects ◽  
Plasma Hormone ◽  
Group B ◽  
Acute Changes ◽  
Multiple Sclerosis Patients ◽  
Time Point

During initiation of interferon-beta (IFN-β) therapy, many multiple sclerosis (MS) patients experience systemic side effects which may depend on the time point of IFN-β injection. We investigated the time course of plasma hormone-, cytokine- and cytokine-receptor concentrations after the first injection of IFN-β either at 8.00 a.m. (group A) or at 6.00 p.m. (group B) and quantified clinical side effects within the first 9 h in 16 medication free patients with relapsing-remitting MS. This investigation was repeated after 6-month IFN-β therapy. Plasma ACTH and cortisol concentrations followed their physiological rhythms, with lower levels in the evening compared to the morning, but raised earlier and stronger in group B after IFN-β administration. IFN-β injection in the evening led to a prompter increase of plasma IL-6 concentrations and temperature during the first hours and correlated to more intense clinical side effects compared to group A. Plasma IL-10 concentrations increased more in group A compared to group B, but sTNF-RI and sTNF-RII concentrations raised 7 h after IFN-β injection only in group B. Acute effects on plasma hormone and cytokine concentrations adapted after 6-month IFN-β treatment, while diurnal variations were still present. Baseline sTNF-RII concentrations were elevated after 6-month IFN-β therapy only in group A. Our results show that time point of IFN-β injection has differential effects on acute changes of plasma hormone and cytokine concentrations and is related to systemic side effects. This may have implications on the tolerability and effectiveness of IFN-β therapy. Multiple Sclerosis 2007; 13: 1138—1145. http://msj.sagepub.com

scholarly journals AB1040 COEXISTENCE OF DEMYELINATION DISEASE AND FAMILIAL MEDITERRANEAN FEVER

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1811.3-1812
Author(s):  
C. Korkmaz ◽  
D. Üsküdar Cansu ◽  
S. Canbaz Kabay
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
General Population ◽  
Familial Mediterranean Fever ◽  
Mefv Gene ◽  
Central Nervous System Involvement ◽  
Demyelinating Diseases ◽  
Clinical Criteria ◽  
Mediterranean Fever

Background:In the course of familial Mediterranean fever (FMF), the frequency of other inflammatory diseases increases compared to the general population. Multiple sclerosis (MS) or demyelinating diseases (DD) of central nervous system (CNS) are also more common in FMF patients than in the general population.Objectives:In this study, we would like to report 5 cases with MS/DD accompanied by FMF or MEFV mutations in two families.Methods:4 patients with FMF and 1 patient with MEFV mutation were included in this study. The patients with FMF were diagnosed according to Tell-Hashomer clinical criteria for FMF. The diagnosis of MS was made according to McDonald criteria.Results:The clinical features of the patients were shown in Table 1.Conclusion:FMF and MS/DD are characterized by repetitive attacks. Familial association can be seen in 12% of patients with MS (1). This is related to both HLA and non-HLA-related genetic tendency. The probability of developing MS increased 4 times in FMF patients (2). This seems to be related to the presence of MEFV gene creating a pro-inflammatory background. In such family samples, combining HLA and non-HLA gene related studies with MEFV gene analysis will be useful in common genetic factors investigation.References:[1]Harirchian MH, Fatehi F, Sarraf P, Honarvar NM, Bitarafan S. Worldwide prevalence of familial multiple sclerosis: A systematic review and meta-analysis. Mult Scler Relat Disord. 2018;20:43-47.[2]Akman-Demir G, Gül A, Gürol E, Özdoğan H, Bahar S, et al. Inflammatory/demyelinating central nervous system involvement in familial Mediterranean fever (FMF): coincidence or association? J Neurol 2006;253:928-934.Acknowledgments:NoneDisclosure of Interests:None declared

Interferon-beta treatment for patients with multiple sclerosis: the patients' perceptions of the side-effects

2000 ◽  
Vol 6 (5) ◽  
pp. 349-354 ◽  
Author(s):  
K Gottberg ◽  
A Gardulf ◽  
S Fredrikson
Keyword(s):  
Multiple Sclerosis ◽  
Side Effects ◽  
Interferon Beta ◽  
The Self ◽  
Daily Lives ◽  
Local Tissue ◽  
Relapsing Remitting ◽  
Before And After ◽  
Systemic Side Effects ◽  
Tissue Reactions

The aims of this study were to investigate (i) the self-reported frequency and intensity of systemic side-effects and their impact on the daily lives of patients suffering from Multiple Sclerosis (MS) and undergoing interferon-beta therapy and (ii) the self-reported frequency and perceptions of any local-tissue reactions. Forty patients aged 22-59 years (27 females) with relapsing/remitting MS were consecutively recruited for the study (17 on interferon-beta-1a and 23 on interferon-beta-1b). Two self-administered questionnaires were used before and after 1, 4, 8 and 16 weeks of therapy. The interferon therapy was found to be associated with flu-like symptoms. Most systemic side-effects were reported to be mild and to have little impact on the patients' daily lives. Asthenia and fatigue were more often rated as moderate or severe. The most frequently reported local-tissue side-effects were redness and local pain at the injection sites. A considerable inter-individual variation was found among patients regarding the perceptions of both the systemic and local side-effects. This suggests that it is of importance to identify early those patients who may need more support or other interventions to maintain a successful compliance.

scholarly journals Eosinophilic Gastroenteritis and Familial Mediterranean Fever in a Child With MEFV Gene Mutation

2019 ◽  
Author(s):  
Sanaz Mehrabani ◽  
Mohammad Pornasrollah ◽  
Leila Moslemi
Keyword(s):  
Abdominal Pain ◽  
Familial Mediterranean Fever ◽  
Gene Mutation ◽  
Histopathological Examination ◽  
Mefv Gene ◽  
Eosinophilic Gastroenteritis ◽  
Inflammatory Disorder ◽  
Medical Sciences ◽  
Exact Etiology ◽  
Mediterranean Fever

Eosinophilic gastroenteritis (EG) is a rare inflammatory disorder affecting both children and adults. The exact etiology of the disease is not clear. A child presented with episodic generalized abdominal pain since a year ago without fever at first. After endoscopic and colonoscopic examinations, histopathological examination showed an increased number of eosinophils and diagnosis of EG was made. After elimination of dairy products from his regimen, abdominal pain attacks was reduced, but he got a fever. Familial Mediterranean Fever (FMF) diagnosis was made by genetic evaluation which showed MEV gene mutation. Symptoms were resolved with the treatment of colchicine which confirmed FMF diagnosis. © 2019 Tehran University of Medical Sciences. All rights reserved. Acta Med Iran 2019;57(5):328-331.

scholarly journals Case Report: Efficacy of Rituximab in a Patient With Familial Mediterranean Fever and Multiple Sclerosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Mattia Pozzato ◽  
Emanuele Micaglio ◽  
Chiara Starvaggi Cucuzza ◽  
Alessandro Cagol ◽  
Daniela Galimberti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Familial Mediterranean Fever ◽  
Demyelinating Disease ◽  
Cervical Spinal Cord ◽  
Mefv Gene ◽  
The Body ◽  
Drug Choice ◽  
Mediterranean Fever ◽  
The Right

Familial Mediterranean Fever (FMF) is a genetic autoinflammatory disease characterized by recurrent episodes of fever and serositis caused by mutations in the MEFV gene, while Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the CNS with genetic and environmental etiology. The two diseases rarely occur in association with relevant implications for clinical management and drug choice. In this paper, we present the case of a 53-year-old male with an autosomal dominant FMF since childhood who presented acute paresthesia at the right part of the body. He performed a brain and spinal cord MRI, which showed multiple brain lesions and a gd-enhancing lesion in the cervical spinal cord, and then received a diagnosis of MS. He then started Interferonβ-1a which was effective but not tolerated and caused hepatotoxicity, and then shifted to Rituximab with 3-month clinical and neuroradiological efficacy.

scholarly journals Recurrent Synovitis of Hip and MEFV Gene Related Arthritis in Children

2019 ◽  
Author(s):  
Farhad Salehzadeh ◽  
Mehrdad Mirzarahimi
Keyword(s):  
Autosomal Recessive ◽  
Mefv Gene ◽  
Gene Mutations ◽  
Inflammatory Disorder ◽  
Hip Joints ◽  
Mefv Mutations ◽  
Pathogenic Variants ◽  
Pathologic Findings ◽  
Mediterranean Fever

Abstract Background: Familial Mediterranean fever (FMF) is an autosomal recessive inherited auto inflammatory disorder. Arthritis is the presenting finding of FMF in some patients, and sometimes it remains as the major manifestation of the disorder. This study reports three non-FMF patients with heterozygous MEFV gene mutations and an extraordinary arthritis as a recurrent synovitis of hip (RSH) Methods: During 16-years from 2003 to 2019 at pediatric rheumatologic clinic among 195 recorded files, 3 patients with diagnosis of recurrent synovitis of hip (RSH) were reviewed thoroughly. Peripheral blood was collected from patients and the samples were screened for the 12 common MEFV gene pathogenic variants. Results: This study included three patients, two female and one male with relapsing arthritis that has been located on hip joints as a sole manifestation and pathologic findings of MEFV mutations as follow: A744S, V726A, and R761H. Conclusion: On the basis of possible role of MEFV gene in different rheumatic disease RSH could be considered as a MEFV gene related arthritis. Key words: FMF, MEFV gene, Recurrent synovitis of hip in children

P1689COMPARISON OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS(NSAIDS) AND/OR PAINKILLERS USE BY KIDNEY (KTRS) AND HEART TRANSPLANT RECIPIENTS (HTRS)

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Anna Jędrzejczak ◽  
Wioletta Szczurek ◽  
Michał Zakliczyńśki ◽  
Bartosz Foroncewicz ◽  
Rafał Staros ◽  
...  
Keyword(s):  
Side Effects ◽  
Heart Transplant ◽  
Solid Organ Transplantation ◽  
P Value ◽  
Solid Organ ◽  
Transplant Recipients ◽  
First Choice ◽  
Inflammatory Drugs ◽  
Heart Transplant Recipients ◽  
Anti Inflammatory

Abstract Background and Aims Solid organ transplantation (SOT) has become the therapy of choice for the treatment of end-stage organ failure. The non-steroidal anti-inflammatory drugs (NSAIDs) and over-the- counter (OTC) painkillers are ofenly used. In a group of SOT recipients, co-morbidities and immunosuppression interactions significantly increase the risk of side effects. The aim of the study was to analyze the frequency and reasons of the NSAIDs and/or painkillers use by renal (RTRs) and heart transplant recipients (HTRs). Method This cross-sectional study was perfomed in randomly selected 388 RTRs and 286 HTRs aged from 18 to 82 years. The original annonymus questionnaire consisting of 32 questions related to health status and NSAIDs and/or analgesics use was applied. Questionnaire was distributed in paper-form and completed with the participation of medical worker either in transplant cardiosurgical or renal transplantation center. “R” v. 3.6.1. was used for statistical analysis and p-value <0.05 was considered significant. Results 674 patients were surveyed. All patients: 34,3% (n=231) women and 65,7% (n=443) men in the mean age of 62.27 years completed the questionnaire. 70% (n=451) of respondents declared using NSAIDs and/or analgesics. Furthermore, 87% of participants declared using OTC painkillers. The most frequent causes for using analgesics are listed in Table 1. 68,5% of our SOT recipients declared that they were informed by their doctor about consequences of other drugs used with immunosuppression. 69,9% of HTRs comparing to 54,3% of RTRs ask their doctor before taking analgesics. Nevertheless, the survey also showed that every third patient (31,5%) was not sufficiently informed. Acetaminophen was the first-choice drug taken by 67,6% of patients (Fig. 1). Only 20% of patients declared not using NSAIDs and/or analgesics at all. Conclusion The result of our study indicates high frequency of NSAID and painkillers usage by RTRs and HTRs. Considering potentially harmful influence on transplanted organs, the costs of transplantation and post-trasplant care, the awareness of drug- related side effects or interactions and patients compliance need to be highlighted.

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