Shared genetic factors may not explain the raised risk of comorbid inflammatory diseases in multiple sclerosis

2012 ◽  
Vol 18 (10) ◽  
pp. 1430-1436 ◽  
Author(s):  
H Roshanisefat ◽  
S Bahmanyar ◽  
J Hillert ◽  
T Olsson ◽  
S Montgomery
Keyword(s):  
Multiple Sclerosis ◽  
Genetic Factors ◽  
Cox Regression ◽  
Disease Risk ◽  
Inflammatory Diseases ◽  
Inflammatory Conditions ◽  
Disease Characteristics ◽  
Immune Mediated ◽  
Risk Patients ◽  
Shared Genetic

Background: Comorbid inflammatory conditions in multiple sclerosis (MS) patients suggest shared risks with MS. Objective: To estimate if the risk of immune-mediated disease in MS patients and their parents is increased. Methods: Swedish register data were analysed using Cox regression to estimate immune-mediated disease risk among 11284 fathers and 12006 mothers of MS patients, compared with 123158 fathers and 129409 mothers of index subjects without MS. Similar analyses were conducted among 20276 index subjects with MS and 203951 without. Results: Parents of patients with MS did not have a significantly altered immune-mediated disease risk. Patients with MS had a consistently raised risk for several immune-mediated diseases: ulcerative colitis, Crohn’s disease, type 1 diabetes, psoriasis, polyarthritis nodosa and pemphigoid. The risk was more pronounced for diseases diagnosed subsequent to MS onset. Conclusion: The increased occurrence of other immune-mediated diseases in MS patients may not be due to shared genetic factors and surveillance bias is likely to be the main or possibly the entire explanation. If not entirely explained by surveillance bias, a modestly raised occurrence of comorbid diseases may be due to shared environmental risks or factors related to MS disease characteristics.

scholarly journals Twin Studies in Auto-immune Disease

1994 ◽  
Vol 43 (1-2) ◽  
pp. 71-81 ◽  
Author(s):  
R.D.G. Leslie ◽  
M. Hawa
Keyword(s):  
Environmental Factors ◽  
Lupus Erythematosus ◽  
Genetic Factors ◽  
Disease Risk ◽  
Twin Studies ◽  
Identical Twins ◽  
Test Bed ◽  
Immune Mediated ◽  
Organ Specific ◽  
Insulin Dependent

AbstractImmune-mediated diseases affect up to 5% of the population and are a major cause of morbidity and mortality. These diseases can be organ specific, such as insulin-dependent diabetes (IDDM) and non-organ specific, such as Rheumatoid Arthritis (RA). Identical and non-identical twins have been used to establish whether these diseases are determined by genetic or environmental factors. The results of these studies have been collated in a new section of the Mendel Institute in Rome.Diseases included in these studies included IDDM, RA, Systemic Lupus Erythematosus (SLE), Multiple Sclerosis (MS) and Myasthenia. Striking differences in concordance rates between identical and non-identical twins in all these studies suggest that genetic factors are important in causing these diseases. All the diseases are known to be associated with HLA genes on chromosome 6 which may account for some or all of the genetic susceptibility. However, in the majority of pairs the affected twin has an unaffected co-twin. These observations suggest that non-genetically determined factors, probably environmental factors and not somatic mutations, are critical. The study of unaffected co-twins, who are at high disease-risk, has allowed the identification of changes which precede and predict the clinical disease. The immune-mediated destruction in many of these diseases is probably caused by T-lymphocytes. Twin studies have shown the importance of genetic factors in determining T-cell responses. Identical twins should, therefore, provide the perfect test bed to assess the role of T-cells in immune-mediated diseases.

scholarly journals Neuropsychiatric manifestations of depression in multiple sclerosis: neuroinflammatory, neuroendocrine, and neurotrophic mechanisms in the pathogenesis of immune-mediated depression

2007 ◽  
Vol 9 (2) ◽  
pp. 125-139
Keyword(s):  
Multiple Sclerosis ◽  
Treatment Strategies ◽  
Causative Role ◽  
Inflammatory Conditions ◽  
Novel Treatment ◽  
Immune Mediated ◽  
Treatment Of Depression ◽  
Neuropsychiatric Manifestations ◽  
Novel Treatment Strategies ◽  
Positive Effect

Evidence suggests that depression in multiple sclerosis (MS) is largely biologically mediated by some of the same processes involved in the immunopathogenesis of this neurologic disease. In particular, the increase in proinflammatory cytokines, activation of the hypothalamic-pituitary-adrenal (HPA) axis, and reduction in neurotrophic factors that occur in MS may each account for the increased rate of depression seen in MS. The possible contributions of these neuroinflammatory, neuroendocrine, and neurotrophic mechanisms suggest a diverse array of novel treatment strategies for depression, both in the context of inflammatory conditions as well as in idiopathic depression. Furthermore, if such processes in MS play a causative role in the pathogenesis of depression, and depression in turn has affects on neurophysiological processes related to immune function, then treatment of depression might have a positive effect on MS disease progression. This makes treating MS depression a neuropsychiatric imperative.

scholarly journals IBD considerations in spondyloarthritis

2020 ◽  
Vol 12 ◽  
pp. 1759720X2093941
Author(s):  
Caroline Di Jiang ◽  
Tim Raine
Keyword(s):  
Inflammatory Diseases ◽  
Drug Dosing ◽  
Inflammatory Conditions ◽  
Gastrointestinal Pathology ◽  
Immune Mediated ◽  
Form Part ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Gastrointestinal Inflammation ◽  
The Difference

Spondyloarthritis (SpA) may be regarded a family of auto-inflammatory conditions with inflammation focused on the joints. These form part of a wider family of immune-mediated inflammatory diseases, which include inflammatory bowel diseases (IBD). These conditions share common elements of pathophysiology and it is perhaps unsurprising, therefore, that individuals with SpA frequently manifest gastrointestinal inflammation, to which the physician managing the patient with SpA must be alert. In this article, we review the shared epidemiology and pathophysiology of these conditions, before discussing approaches to diagnosis and management of inflammatory gastrointestinal pathology in patients seen in rheumatology clinics. In particular, we discuss the difference between non-specific gastrointestinal inflammation commonly described in this patient group and the more specific diagnosis of Crohn’s disease or ulcerative colitis. We describe the appropriate diagnostic workup for patients suspected of having IBD. In addition, we discuss how a diagnosis of IBD can inform treatment selection, highlighting important differences in treatment choice, drug dosing, monitoring and drug safety for this particular comorbid patient population.

scholarly journals Impact of red meat, processed meat and fibre intake on risk of late-onset chronic inflammatory diseases: prospective cohort study on lifestyle factors using the Danish ‘Diet, Cancer and Health’ cohort (PROCID-DCH):protocol

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e024555 ◽  
Author(s):  
Nathalie Fogh Rasmussen ◽  
Katrine Hass Rubin ◽  
Maria Stougaard ◽  
Anne Tjønneland ◽  
Egon Stenager ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cohort Study ◽  
Prospective Cohort ◽  
Disease Risk ◽  
Late Onset ◽  
Inflammatory Diseases ◽  
Red Meat ◽  
Processed Meat ◽  
Chronic Inflammatory Diseases

IntroductionChronic inflammatory diseases (CIDs) (Crohn’s disease, ulcerative colitis, psoriasis, psoriatic arthritis, rheumatoid arthritis and multiple sclerosis) are diseases of the immune system that have some shared genetic and environmental predisposing factors, but still few studies have investigated the effects of lifestyle on disease risk of several CIDs. The primary aim of this prospective cohort study is to investigate the impact of fibre, red meat and processed meat on risk of late-onset CID, with the perspective that results of this study can contribute in supporting future diet recommendations for effective personalised prevention.Methods and analysisThe study will use data from 57 053 persons from the prospective Danish cohort study ‘Diet, Cancer and Health’ together with National Health Registry data. The follow-up period is from December 1993 to December 2018. Questionnaire data on diet and lifestyle were collected at entry to the Diet, Cancer and Health study. The outcome CID is defined as having a diagnosis of one of the CIDs registered in the National Patient Registry or, for multiple sclerosis, in the Danish Multiple Sclerosis Registry during follow-up and being treated with a drug used for the specific disease. The major outcome of the analyses will be to detect variability in risk of late onset of any CID and, if power allows, disease risk of late onset of each CID diagnosis between persons with different fibre and red meat, and processed meat intake. The outcome will be adjusted for age, sex, body mass index, physical activity, energy, alcohol, fermented dairy products, education, smoking status, hormone replacement therapy and comorbidity.Ethics and disseminationThe study is approved by the Danish Data Protection Agency (2012-58-0018). The core study is an open register-based cohort study. The study does not need approval from the Ethics committee or Institutional Review Board by Danish law. Study findings will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences.Trial registration numberNCT03456206; Post-results.

Increased Risk of Autoimmune Disease in Families with Wegener’s Granulomatosis

2010 ◽  
Vol 37 (12) ◽  
pp. 2553-2558 ◽  
Author(s):  
ANN KNIGHT ◽  
SVEN SANDIN ◽  
JOHAN ASKLING
Keyword(s):  
Inflammatory Disease ◽  
Wegener’S Granulomatosis ◽  
Cox Regression ◽  
Disease Risk ◽  
Inflammatory Diseases ◽  
Population Level ◽  
Wegener's Granulomatosis ◽  
First Degree Relatives ◽  
Increased Risk ◽  
Autoimmune Inflammatory Disease

Objective.The etiology of Wegener’s granulomatosis (WG) is unknown. Susceptibility genes for WG that also affect the risks of other autoimmune/inflammatory diseases have been identified, indicating the existence of shared interdisease genetic susceptibilities. To determine the effect, on a population level, of shared susceptibility on disease risk, we assessed the occurrence of autoimmune/inflammatory disease in first-degree relatives of patients with WG.Methods.In the Swedish Hospital Discharge Register we identified 2288 individuals discharged with the diagnosis of WG between 1970 and 2003. Through linkage to the Swedish Multi-generation Register we identified 787 parents, 1212 siblings, and 3650 children of these patients. From the Register of Total Population we identified 10 controls for each patient with WG, and 65,000 of their first-degree relatives. Through linkage to the nationwide Outpatients Register, we identified autoimmune/inflammatory disease among all relatives. Relative risks were estimated as hazard ratio (HR) using Cox regression. The study period was 2001–2006.Results.Biological first-degree relatives of patients with WG were at a moderately increased risk of any autoimmune/inflammatory disease (HR 1.32, 95% CI 1.18–1.49), including specific associations with, for example, multiple sclerosis (HR 1.92, 95% CI 1.16–3.16), Sjögren’s syndrome (HR 2.00, 95% CI 1.07–3.73), and seropositive rheumatoid arthritis (HR 1.54, 95% CI 1.09–2.19).Conclusion.Relatives of patients with WG are at increased risk of being diagnosed with other autoimmune/inflammatory diseases, indicating shared susceptibility between WG and other auto-immune/inflammatory disease.

scholarly journals Role of CCR2 in Inflammatory Conditions of the Central Nervous System

2014 ◽  
Vol 34 (9) ◽  
pp. 1425-1429 ◽  
Author(s):  
Hannah X Chu ◽  
Thiruma V Arumugam ◽  
Mathias Gelderblom ◽  
Tim Magnus ◽  
Grant R Drummond ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Ischemic Stroke ◽  
Inflammatory Diseases ◽  
Protective Effects ◽  
Cns Inflammation ◽  
Inflammatory Conditions ◽  
The Central Nervous System ◽  
Effective Development

CC chemokine receptor 2 (CCR2) plays important roles in extravasation and transmigration of monocytes under inflammatory conditions. CCR2 and its ligands have been extensively studied in a range of inflammatory diseases in the central nervous system (CNS), including multiple sclerosis, Alzheimer's disease and ischemic stroke. This brief review summarizes our current understanding of the physiologic and pathologic roles of CCR2, focusing on its involvement in CNS inflammatory diseases. There appears to be a rationale for exploring therapies involving CCR2 inhibition in multiple sclerosis and ischemic stroke, but there is also evidence for immunomodulatory and protective effects of CCR2 activity during CNS inflammation. The critical balance between protective and detrimental roles of CCR2-dependent recruitment of leukocytes must therefore be carefully examined to guide safe and effective development of any therapies involving CCR2 modulation.

Toll-Like Receptor 4 (TLR4) and AMPK Relevance in Cardiovascular Disease

2021 ◽  
Author(s):  
Haleh Vaez ◽  
Hamid Soraya ◽  
Alireza Garjani ◽  
Tooba Gholikhani
Keyword(s):  
Cardiovascular Diseases ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Adenosine Monophosphate ◽  
Ampk Signaling ◽  
Inflammatory Conditions ◽  
Immune Mediated ◽  
Energy Sensor

Toll-like receptors (TLRs) are essential receptors of the innate immune system, playing a significant role in cardiovascular diseases. TLR4, with the highest expression among TLRs in the heart, has been investigated extensively for its critical role in different myocardial inflammatory conditions. Studies suggest that inhibition of TLR4 signaling pathways reduces inflammatory responses and even prevents additional injuries to the already damaged myocardium. Recent research results have led to a hypothesis that there may be a relation between TLR4 expression and 5' adenosine monophosphate-activated protein kinase (AMPK) signaling in various inflammatory conditions, including cardiovascular diseases. AMPK, as a cellular energy sensor, has been reported to show anti-inflammatory effects in various models of inflammatory diseases. AMPK, in addition to its physiological acts in the heart, plays an essential role in myocardial ischemia and hypoxia by activating various energy production pathways. Herein we will discuss the role of TLR4 and AMPK in cardiovascular diseases and a possible relation between TLRs and AMPK as a novel therapeutic target. In our opinion, AMPK-related TLR modulators will find application in treating different immune-mediated inflammatory disorders, especially inflammatory cardiac diseases, and present an option that will be widely used in clinical practice in the future.

scholarly journals Myelin insulation as a risk factor for axonal degeneration in autoimmune demyelinating disease

2021 ◽  
Author(s):  
Erik Schaeffner ◽  
Julia Edgar ◽  
Maria Lehning ◽  
Judith Strauss ◽  
Mar Bosch-Queralt ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Risk Factor ◽  
Autoimmune Disease ◽  
Clinical Outcome ◽  
Axonal Degeneration ◽  
Demyelinating Disease ◽  
Demyelinating Diseases ◽  
Extracellular Milieu ◽  
Inflammatory Conditions ◽  
Immune Mediated

Axonal degeneration determines the clinical outcome of multiple sclerosis (MS), and is thought to result from exposure of denuded axons to immune-mediated damage. We challenge this view after finding in MS and its mouse models that myelin itself increases the risk of axons to degenerate under inflammatory conditions. We propose a model for demyelinating diseases in which for axons that remain myelinated, and thus shielded from the extracellular milieu, dependence from oligodendroglial support turns fatal in an autoimmune disease environment.

scholarly journals Expression and Function of Host Defense Peptides at Inflammation Sites

2019 ◽  
Vol 21 (1) ◽  
pp. 104 ◽  
Author(s):  
Suhanya V. Prasad ◽  
Krzysztof Fiedoruk ◽  
Tamara Daniluk ◽  
Ewelina Piktel ◽  
Robert Bucki
Keyword(s):  
Host Defense ◽  
Inflammatory Diseases ◽  
Current Data ◽  
Host Defense Peptides ◽  
Host Protection ◽  
Inflammatory Conditions ◽  
Molecular Events ◽  
Immune Mediated ◽  
Defense Peptides ◽  
And Function

There is a growing interest in the complex role of host defense peptides (HDPs) in the pathophysiology of several immune-mediated inflammatory diseases. The physicochemical properties and selective interaction of HDPs with various receptors define their immunomodulatory effects. However, it is quite challenging to understand their function because some HDPs play opposing pro-inflammatory and anti-inflammatory roles, depending on their expression level within the site of inflammation. While it is known that HDPs maintain constitutive host protection against invading microorganisms, the inducible nature of HDPs in various cells and tissues is an important aspect of the molecular events of inflammation. This review outlines the biological functions and emerging roles of HDPs in different inflammatory conditions. We further discuss the current data on the clinical relevance of impaired HDPs expression in inflammation and selected diseases.

Genetics and Epidemiology of Multiple Sclerosis

2016 ◽  
Author(s):  
Gabriele C. Deluca ◽  
Richard L. Yates ◽  
A. Dessa Sadovnick
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Genetic Factors ◽  
Demyelinating Disease ◽  
Disease Risk ◽  
Multiple Sclerosis Pathogenesis ◽  
Multiple Sclerosis Disease ◽  
The Central Nervous System ◽  
Epidemiologic Features ◽  
Shed Light

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. Despite decades of research, its etiology remains unknown. It has been established that environmental and genetic factors contribute to multiple sclerosis disease risk. Although the identification of risk factors for multiple sclerosis has not yet radically advanced understanding of the pathophysiology, it has shed light on the complex epidemiology of this disease. This chapter highlights key epidemiologic features of multiple sclerosis, with a focus on environmental and genetic factors known to influence disease risk. The interplay between environmental and genetic factors in multiple sclerosis pathogenesis is discussed.

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