Smoking and risk of treatment-induced neutralizing antibodies to interferon β-1a

Hedström, Anna Karin; Ryner, Malin; Fink, Katarina; Fogdell‐Hahn, Anna; Alfredsson, Lars; Olsson, Tomas; Hillert, Jan

doi:10.1177/1352458513498635

Cited by 53 publications

(33 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Smoking has been reported to increase the risk for developing anti-interferon neutralizing antibodies [23, 24]. We had self-reported smoking status for 903 subjects.…”

Section: Discussionmentioning

confidence: 99%

Humoral Responses to Diverse Autoimmune Disease-Associated Antigens in Multiple Sclerosis

et al. 2015

View full text Add to dashboard Cite

To compare frequencies of autoreactive antibody responses to endogenous disease-associated antigens in healthy controls (HC), relapsing and progressive MS and to assess their associations with clinical and MRI measures of MS disease progression.MethodsThe study analyzed 969 serum samples from 315 HC, 411 relapsing remitting MS (RR-MS), 128 secondary progressive MS (SP-MS), 33 primary progressive MS (PP-MS) and 82 patients with other neurological diseases for autoantibodies against two putative MS antigens CSF114(Glc) and KIR4.1a and KIR4.1b and against 24 key endogenous antigens linked to diseases such as vasculitis, systemic sclerosis, rheumatoid arthritis, Sjogren’s syndrome, systemic lupus erythematosus, polymyositis, scleroderma, polymyositis, dermatomyositis, mixed connective tissue disease and primary biliary cirrhosis. Associations with disability and MRI measures of lesional injury and neurodegeneration were assessed.ResultsThe frequencies of anti-KIR4.1a and anti-KIR4.1b peptide IgG positivity were 9.8% and 11.4% in HC compared to 4.9% and 7.5% in RR-MS, 8.6% for both peptides in SP-MS and 6.1% for both peptides in PP-MS (p = 0.13 for KIR4.1a and p = 0.34 for KIR4.1b), respectively. Antibodies against CSF114(Glc), KIR4.1a and KIR4.1b peptides were not associated with MS compared to HC, or with MS disease progression. HLA DRB1*15:01 positivity and anti-Epstein Barr virus antibodies, which are MS risk factors, were not associated with these putative MS antibodies.ConclusionsAntibody responses to KIR4.1a and KIR4.1b peptides are not increased in MS compared to HC nor associated with MS disease progression. The frequencies of the diverse autoreactive antibodies investigated are similar in MS and HC.

show abstract

“…Smoking has been reported to increase the risk for developing anti-interferon neutralizing antibodies [23, 24]. We had self-reported smoking status for 903 subjects.…”

Section: Discussionmentioning

confidence: 99%

Humoral Responses to Diverse Autoimmune Disease-Associated Antigens in Multiple Sclerosis

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Another example when the cross-analysis of different data sets available on patients in the SMSreg has allowed new discoveries is the identification of different HLA genotypes that increase the risk of antibodies to different interferon beta species (22) and that this risk is also influenced by smoking (23).…”

Section: Anti-drug Antibodiesmentioning

confidence: 99%

The Swedish MS registry – clinical support tool and scientific resource

2015

View full text Add to dashboard Cite

The Swedish MS registry (SMSreg) is designed to assure quality health care for patients with multiple sclerosis (MS). It has been active since 2001 and web-based since 2004. It runs on government funding only and is used in all Swedish neurology departments. The SMSreg currently includes data on 14,500 of Sweden's estimated 17,500 prevalent patients with MS. One important function of SMSreg, to which participation is voluntary, is to serve as a tool for decision support and to provide an easy overview of the patient information needed at clinical visits. This is its core feature and explains why the majority of Swedish MS specialists contribute data. Another success factor for SMSreg is that entered data can be readily accessed, either through a query function into Excel format or through a set of predesigned tables and diagrams in which parameters can be selected. Recent development includes a portal allowing patients to view a summary of their registered data and to report a set of patient-reported outcomes. SMSreg data have been used in close to 100 published scientific reports. Current projects include an incidence cohort (EIMS), post-marketing cohorts of patients on novel disease-modifying drugs (IMSE), and a prevalence cohort (GEMS). As these studies combine physical sampling and questionnaire data with clinical documentation and possible linkage to other public registries, together they provide an excellent platform for integrated MS research.

show abstract

“…Smoking is a risk factor for MS and stronger if combined with the well‐known HLA associations. Smoking is also a risk factor for developing ADA, both in IFN‐ β ‐ and in natalizumab‐treated MS patients . Understanding the role the lung, or in these cases the smoke‐irritated lung, has in regulating the immune system during autoimmune reactions may inform on the mechanisms underlying ADA induction.…”

Section: Risk Factors For Ada In Msmentioning

confidence: 99%

Antidrug Antibodies: B Cell Immunity Against Therapy

Fogdell‐Hahn

2015

Scand J Immunol

View full text Add to dashboard Cite

Chronic inflammatory diseases are now treated with a range of different biopharmaceuticals, often requiring lifelong parenteral administrations. This exposure to drugs is unnatural and can trigger the immune system and result in the formation of antidrug antibodies. Drug-specific antibodies will, if of sufficiently high titre and affinity, block the intended effect of the drug, increase its clearance and make continued treatment worthless. We expect the immune system to react towards therapies against which tolerance has never been established, which is the case for factor VIII treatment in patients with haemophilia A. However, even biopharmaceutical molecules that we should be tolerant against can elicit antidrug antibodies, for instance in treatment of multiple sclerosis patients with recombinant human interferon-beta. Possible immunological mechanisms behind the breaking of tolerance against drugs, the impact this has on continuous treatment success, clinical practice and drug development, will be discussed in this review.

show abstract

Smoking and risk of treatment-induced neutralizing antibodies to interferon β-1a

Abstract: The finding that current smokers have an increased risk of developing NAbs to IFNβ-1a has implications, both for the practical care and the treatment of MS; it also provides an interesting perspective of the lungs as an immune-reactive organ, reacting upon irritation.

Cited by 53 publications

References 23 publications

Humoral Responses to Diverse Autoimmune Disease-Associated Antigens in Multiple Sclerosis

Humoral Responses to Diverse Autoimmune Disease-Associated Antigens in Multiple Sclerosis

The Swedish MS registry – clinical support tool and scientific resource

Antidrug Antibodies: B Cell Immunity Against Therapy

Contact Info

Product

Resources

About