The influence of human leukocyte antigen-DRB1*15:01 and its interaction with smoking in MS development is dependent on DQA1*01:01 status

2019 ◽  
Vol 26 (13) ◽  
pp. 1638-1646 ◽  
Author(s):  
Anna Karin Hedström ◽  
Ola Hössjer ◽  
Jan Hillert ◽  
Pernilla Stridh ◽  
Ingrid Kockum ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Population Based ◽  
Case Control ◽  
Case Control Studies ◽  
Swedish Population ◽  
Leukocyte Antigen ◽  
Smoking Interaction ◽  
Additive Scale

Background: HLA-DRB1*15:01, absence of HLA-A*02:01, and smoking interact to increase multiple sclerosis (MS) risk. Objective: To analyze whether MS-associated human leukocyte antigen (HLA) alleles, apart from DRB1*15:01 and absence of A*02:01, interact with smoking in MS development, and to explore whether the established HLA-smoking interaction is affected by the DQA1*01:01 allele, which confers a protective effect only in the presence of DRB1*15:01. Methods: In two Swedish population-based case–control studies (5838 cases, 5412 controls), subjects with different genotypes and smoking habits were compared regarding MS risk, by calculating odds ratios with 95% confidence intervals employing logistic regression. Interaction on the additive scale between different genotypes and smoking was evaluated. Results: The DRB1*08:01 allele interacted with smoking to increase MS risk. The interaction between DRB1*15:01 and both the absence of A*02:01 and smoking was confined to DQA1*01:01 negative subjects, whereas no interactions occurred among DQA1*01:01 positive subjects. Conclusion: Multifaceted interactions take place between different class II alleles and smoking in MS development. The influence of DRB1*15:01 and its interaction with the absence of A*02:01 and smoking is dependent on DQA1*01:01 status which may be due to differences in the responding T-cell repertoires.

scholarly journals DRB1–environment interactions in multiple sclerosis etiology: results from two Swedish case–control studies

2021 ◽  
pp. jnnp-2020-325676
Author(s):  
Anna Karin Hedström ◽  
Jan Hillert ◽  
Nicole Brenner ◽  
Julia Butt ◽  
Tim Waterboer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Environmental Factors ◽  
Environmental Factor ◽  
Population Based ◽  
Case Control ◽  
Case Control Studies ◽  
Adolescent Overweight ◽  
Log Odds ◽  
Antibody Levels ◽  
Additive Scale

ObjectiveWe aimed to investigate the influence of environmental risk factors for multiple sclerosis (MS) in different genetic contexts, and study if interactions between environmental factors and human leucocyte antigen (HLA) genes differ in magnitude according to heterozygocity and homozygocity for HLA-DRB1*15:01.MethodsUsing population-based case–control studies (6985 cases, 6569 controls), subjects with different genotypes and smoking, EBNA-1 status and adolescent Body Mass status, were compared regarding MS risk, by calculating OR with 95% CI employing logistic regression. The interaction between different genotypes and each environmental factor was evaluated on the additive scale.ResultsThe effect of each DRB1*15:01 allele on MS risk was additive on the log-odds scale for each additional allele. Interaction between DRB1*15:01 and each assessed environmental factor was of similar magnitude regardless of the number of DRB1*15:01 alleles, although ORs were affected. When any of the environmental factors were present in DRB1*15:01 carriers without the protective A*02:01 allele, a three-way interaction occurred and rendered high ORs, especially among DRB1*15:01 homozygotes (OR 20.0, 95% CI 13.1 to 30.5 among smokers, OR 21.9, 95% CI 15.0 to 31.8 among those with elevated EBNA-1 antibody levels, and OR 44.3, 95% CI 13.5 to 145 among those who reported adolescent overweight/obesity).ConclusionsThe strikingly increased MS risk among DRB*15:01 homozygotes exposed to any of the environmental factors is a further argument in favour of these factors acting on immune-related mechanisms. The data further reinforce the importance of preventive measures, in particular for those with a genetic susceptibility to MS.

scholarly journals The increased risk of multiple sclerosis associated with HLA-DRB1*15:01 and smoking is modified by alcohol consumption

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Karin Hedström ◽  
Tomas Olsson ◽  
Lars Alfredsson
Keyword(s):  
Multiple Sclerosis ◽  
Alcohol Consumption ◽  
Human Leukocyte ◽  
Population Based ◽  
Inverse Association ◽  
Swedish Population ◽  
Logistic Regression Models ◽  
Leukocyte Antigen ◽  
Increased Risk ◽  
Incident Cases

AbstractPrevious studies have observed an inverse association between alcohol consumption and multiple sclerosis (MS) risk. We aimed to investigate possible interactions between alcohol consumption, MS-associated human leukocyte antigen (HLA) genes and smoking regarding MS risk. We used a Swedish population-based case–control study (2059 incident cases, 2887 controls) matched by age, sex, and residential area. Subjects with different genotypes and alcohol consumption habits were compared regarding MS risk, by calculating odds ratios with 95% confidence intervals using logistic regression models. Interaction on the additive scale between non-drinking and both genotype and smoking were assessed by calculating the attributable proportion due to interaction (AP). There was a dose-dependent inverse association between alcohol consumption and MS risk (p for trend < 0.0001). A potentiating effect was observed between non-drinking and presence of DRB1*15:01 (AP 0.3, 95% CI 0.2–0.5) which was of similar magnitude irrespective of smoking habits. Non-drinking also interacted with smoking to increase MS risk (AP 0.2, 95% CI 0.06–0.4). Non-drinking interacts with DRB1*15:01 and smoking to increase the risk of MS. Better understanding of the mechanisms behind our findings may help to define ways to achieve protection against MS by other means than alcohol consumption.

Nicotine might have a protective effect in the etiology of multiple sclerosis

2013 ◽  
Vol 19 (8) ◽  
pp. 1009-1013 ◽  
Author(s):  
AK Hedström ◽  
J Hillert ◽  
T Olsson ◽  
L Alfredsson
Keyword(s):  
Multiple Sclerosis ◽  
Immune Responses ◽  
Protective Effect ◽  
Lower Risk ◽  
Population Based ◽  
Case Control ◽  
Case Control Studies ◽  
Swedish Population ◽  
Moist Snuff ◽  
High Doses

Objective: The use of moist snuff is common in Sweden and leads to exposure to high doses of nicotine. Recent studies indicate that exposure to nicotine could modulate immune responses. The aim of this study was to investigate the influence of snuff use on the risk of developing multiple sclerosis (MS), taking smoking habits into consideration. Methods: In two Swedish population-based, case-control studies (7883 cases, 9437 controls), subjects with different snuff use habits were compared regarding MS risk, by calculating odds ratios (ORs) with 95% confidence intervals (CIs). Results: Snuff-takers have a decreased risk of developing MS compared with those who have never used moist snuff (OR 0.83, 95% CI 0.75–0.92), and we found clear evidence of an inverse dose-response correlation between cumulative dose of snuff use and the risk of developing the disease. We further observed that subjects who combined smoking and snuff use had a significantly lower risk for MS than smokers who had never used moist snuff, also after adjustment for amount of smoking. Conclusions: Our results add evidence to the hypothesis that nicotine exerts anti-inflammatory and immune-modulating effects in a way that might decrease the risk of developing MS.

scholarly journals Antibody response to common viruses and human leukocyte antigen-DRB1 in pediatric multiple sclerosis

2012 ◽  
Vol 19 (7) ◽  
pp. 891-895 ◽  
Author(s):  
Emmanuelle Waubant ◽  
Ellen M Mowry ◽  
Lauren Krupp ◽  
Tanuja Chitnis ◽  
E Ann Yeh ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Antibody Response ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Humoral Response ◽  
Nuclear Antigen ◽  
Leukocyte Antigen ◽  
Epstein Barr ◽  
Humoral Responses ◽  
Hsv 1

Background: As remote infections with common herpes viruses are associated with modulation of the risk of multiple sclerosis (MS), we hypothesized that antibody concentrations against these viruses may further modify risk. As many common viruses are first encountered during childhood, pediatric MS offer a unique opportunity to investigate more closely their influence on susceptibility. Our aim was to determine if MS patients who were positive for these viruses had higher levels of antibodies to these viruses. We also assessed whether human leukocyte antigen (HLA)-DRB1*1501 genotype influenced viral antibody levels. Methods: Antibody response levels toward Epstein Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV)-1, and HLA-DRB1*1501 status were determined in pediatric MS patients ( n=189) and controls ( n=38). Multivariate analyses were used, adjusted for age, gender, race, ethnicity and use of disease-modifying therapies. Results: The antibody concentrations against EBV (Epstein-Barr nuclear antigen 1 (EBNA-1), viral capsid antigen (VCA) and early antigen (EA)), CMV and HSV-1 were similar between pediatric MS patients and controls positive for seroconversion against the virus of interest. EBNA-1 humoral responses were higher in HLA-DRB1 positive individuals ( p=0.005) whereas other viral humoral responses were similar in HLA-DRB1 positive and negative individuals. Conclusion: Among those positive for EBNA-1, MS patients did not have higher levels of antibody response to EBNA-1: however, titers for EBNA-1 were higher in those who were HLA-DRB1 positive. This suggests that genotype might influence the humoral response to EBV. Whether other genotypes influence antibody response to other viruses remains to be determined.

scholarly journals Multiple sclerosis: disease modifying therapy and the human leukocyte antigen

2018 ◽  
Vol 76 (10) ◽  
pp. 697-704 ◽  
Author(s):  
Lineu Cesar Werneck ◽  
Paulo José Lorenzoni ◽  
Cláudia Suemi Kamoi Kay ◽  
Rosana Herminia Scola
Keyword(s):  
Multiple Sclerosis ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Class I ◽  
Interferon Β ◽  
Leukocyte Antigen ◽  
Specific Subset ◽  
Hla Type ◽  
Disease Modifying

ABSTRACT Objective: To investigate the potential relationship between the human leukocyte antigen (HLA) type (class I and II) and the response to several disease-modifying therapies (DMTs) in patients with multiple sclerosis (MS). Methods: We analyzed clinical data of 87 patients with MS at the beginning and end of each type of DMT including the disease duration, Expanded Disability Status Scale and Multiple Sclerosis Severity Score (MSSS). Genotyping of HLA-DRB1, HLA-DPB1, HLA-DQB1, HLA-A, HLA-B and HLA-C alleles were identified using high-resolution techniques. Statistical correlation between the HLA type and response to DMTs was done using the initial and final MSSS. Results: Statistical relationships (p < 0.05) were found for only 15 of 245 alleles tested. There was a reduction in the MSSS for patients treated with corticosteroids (DRB1*15:01, DPB1*04:01, DQB1*02:01 and DQB1*03:01), azathioprine (DRB1*03:01, DPB1*04:01, DQB1*03:02, DQB1*06:02, HLA-C*07:02), interferon β-1a 22 mcg (DRB1*11:04, DQB1*03:01 and DQB1*03:02), interferon β-1a 30 mcg (DPB1*02:01, HLA-C*05:01) and interferon β-1b (DQB1*02:01). Conclusion: These findings suggest a few relationships between the HLA and response to DMTs in the disability for some types of HLA class I and II alleles in a specific subset of MS patients.

scholarly journals Smoking and two human leukocyte antigen genes interact to increase the risk for multiple sclerosis

Brain ◽  
2011 ◽  
Vol 134 (3) ◽  
pp. 653-664 ◽  
Author(s):  
Anna Karin Hedström ◽  
Emilie Sundqvist ◽  
Maria Bäärnhielm ◽  
Nina Nordin ◽  
Jan Hillert ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Leukocyte Antigen
Sign in / Sign up

Export Citation Format

Share Document