Human host defence peptide LL37 and anti-cyclic citrullinated peptide antibody in early inflammatory arthritis

ObjectiveAntibodies to citrullinated peptides (anti-CCP) develop in individuals predisposed to rheumatoid arthritis (RA). Neutrophil extracellular traps are a major source of citrullinated antigens and the immunomodulatory host defence peptide LL-37. Vitamin D regulates LL-37 expression. This study...

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Published inRheumatic & musculoskeletal diseases open Vol. 5; no. 1; p. e000874
Main Authors Hitchon, Carol A, Meng, Xiaobo, El Gabalawy, Hani S, Larcombe, Linda
Format Journal Article
LanguageEnglish
Published England EULAR 01.04.2019
BMJ Publishing Group LTD
BMJ Publishing Group
SeriesOriginal article
Subjects
Age
Aged
ant-CCP
Anti-Citrullinated Protein Antibodies - blood
Anti-Citrullinated Protein Antibodies - immunology
Antibodies
Antimicrobial agents
Antimicrobial Cationic Peptides - blood
Antimicrobial Cationic Peptides - metabolism
Arthritis - blood
Arthritis - etiology
Arthritis - metabolism
Arthritis - pathology
Autoantibodies - blood
Autoantibodies - immunology
Autoimmunity
Biomarkers
Disease Susceptibility
Early Arthritis
early rheumatoid arthritis
Epitopes - genetics
Epitopes - immunology
Female
Females
Gene expression
Genetic Predisposition to Disease
Health risk assessment
Humans
Inflammation
Laboratories
Male
Middle Aged
Peptides
Polymorphism
Polymorphism, Single Nucleotide
Receptors, Calcitriol - genetics
Regression analysis
Rheumatism
Rheumatoid arthritis
Rheumatology
Severity of Illness Index
Smoking
Tuberculosis
Vitamin D
Vitamin deficiency
United States > US
inflammation
ant-CCP
early rheumatoid arthritis
Online AccessGet full text

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Abstract ObjectiveAntibodies to citrullinated peptides (anti-CCP) develop in individuals predisposed to rheumatoid arthritis (RA). Neutrophil extracellular traps are a major source of citrullinated antigens and the immunomodulatory host defence peptide LL-37. Vitamin D regulates LL-37 expression. This study assessed the associations of LL-37 and anti-CCP, vitamin D metabolites and vitamin D receptor (VDR) polymorphisms in early inflammatory arthritis (EIA).MethodsSerum LL-37, 25-hydroxy-vitamin D (25OHvitD) and anti-CCP were measured by ELISA in treatment naïve EIA (n = 181). VDR single nucleotide polymorphisms (Fok1, Bsm1, Apa1, Taq1, Cdx-2) and HLADRB1 shared epitope (SE) alleles were detected by DNA amplification. Associations were tested in multivariable models. Median (25%, 75%) or percentiles are reported.ResultsParticipants (70 % female, age 56 [45, 66] years, disease activity score [DAS28ESR3var] 3.7 [2.8, 4.8], 41 % anti-CCP positive, 68 % RA) had low serum 25OHvitD; 20.5 nmol/L (13.9, 29.0). In multivariable models, controlling for age, sex, SE, smoking and vitamin D deficiency, LL37 level (top quartile) associated with anti-CCP seropositivity (OR 22; 95% CI 4 to 104).ConclusionsLevels of circulating LL-37 are associated with anti-CCP seropositivity. LL37 activity may be one mechanism linking infection and toxin exposure to anti-CCP generation.
AbstractList Objective Antibodies to citrullinated peptides (anti-CCP) develop in individuals predisposed to rheumatoid arthritis (RA). Neutrophil extracellular traps are a major source of citrullinated antigens and the immunomodulatory host defence peptide LL-37. Vitamin D regulates LL-37 expression. This study assessed the associations of LL-37 and anti-CCP, vitamin D metabolites and vitamin D receptor (VDR) polymorphisms in early inflammatory arthritis (EIA).Methods Serum LL-37, 25-hydroxy-vitamin D (25OHvitD) and anti-CCP were measured by ELISA in treatment naïve EIA (n = 181). VDR single nucleotide polymorphisms (Fok1, Bsm1, Apa1, Taq1, Cdx-2) and HLADRB1 shared epitope (SE) alleles were detected by DNA amplification. Associations were tested in multivariable models. Median (25%, 75%) or percentiles are reported.Results Participants (70 % female, age 56 [45, 66] years, disease activity score [DAS28ESR3var] 3.7 [2.8, 4.8], 41 % anti-CCP positive, 68 % RA) had low serum 25OHvitD; 20.5 nmol/L (13.9, 29.0). In multivariable models, controlling for age, sex, SE, smoking and vitamin D deficiency, LL37 level (top quartile) associated with anti-CCP seropositivity (OR 22; 95% CI 4 to 104).Conclusions Levels of circulating LL-37 are associated with anti-CCP seropositivity. LL37 activity may be one mechanism linking infection and toxin exposure to anti-CCP generation.
Antibodies to citrullinated peptides (anti-CCP) develop in individuals predisposed to rheumatoid arthritis (RA). Neutrophil extracellular traps are a major source of citrullinated antigens and the immunomodulatory host defence peptide LL-37. Vitamin D regulates LL-37 expression. This study assessed the associations of LL-37 and anti-CCP, vitamin D metabolites and vitamin D receptor (VDR) polymorphisms in early inflammatory arthritis (EIA). Serum LL-37, 25-hydroxy-vitamin D (25OHvitD) and anti-CCP were measured by ELISA in treatment naïve EIA (n = 181). VDR single nucleotide polymorphisms (Fok1, Bsm1, Apa1, Taq1, Cdx-2) and HLADRB1 shared epitope (SE) alleles were detected by DNA amplification. Associations were tested in multivariable models. Median (25%, 75%) or percentiles are reported. Participants (70 % female, age 56 [45, 66] years, disease activity score [DAS28ESR3var] 3.7 [2.8, 4.8], 41 % anti-CCP positive, 68 % RA) had low serum 25OHvitD; 20.5 nmol/L (13.9, 29.0). In multivariable models, controlling for age, sex, SE, smoking and vitamin D deficiency, LL37 level (top quartile) associated with anti-CCP seropositivity (OR 22; 95% CI 4 to 104). Levels of circulating LL-37 are associated with anti-CCP seropositivity. LL37 activity may be one mechanism linking infection and toxin exposure to anti-CCP generation.
ObjectiveAntibodies to citrullinated peptides (anti-CCP) develop in individuals predisposed to rheumatoid arthritis (RA). Neutrophil extracellular traps are a major source of citrullinated antigens and the immunomodulatory host defence peptide LL-37. Vitamin D regulates LL-37 expression. This study assessed the associations of LL-37 and anti-CCP, vitamin D metabolites and vitamin D receptor (VDR) polymorphisms in early inflammatory arthritis (EIA).MethodsSerum LL-37, 25-hydroxy-vitamin D (25OHvitD) and anti-CCP were measured by ELISA in treatment naïve EIA (n = 181). VDR single nucleotide polymorphisms (Fok1, Bsm1, Apa1, Taq1, Cdx-2) and HLADRB1 shared epitope (SE) alleles were detected by DNA amplification. Associations were tested in multivariable models. Median (25%, 75%) or percentiles are reported.ResultsParticipants (70 % female, age 56 [45, 66] years, disease activity score [DAS28ESR3var] 3.7 [2.8, 4.8], 41 % anti-CCP positive, 68 % RA) had low serum 25OHvitD; 20.5 nmol/L (13.9, 29.0). In multivariable models, controlling for age, sex, SE, smoking and vitamin D deficiency, LL37 level (top quartile) associated with anti-CCP seropositivity (OR 22; 95% CI 4 to 104).ConclusionsLevels of circulating LL-37 are associated with anti-CCP seropositivity. LL37 activity may be one mechanism linking infection and toxin exposure to anti-CCP generation.
Objective Antibodies to citrullinated peptides (anti-CCP) develop in individuals predisposed to rheumatoid arthritis (RA). Neutrophil extracellular traps are a major source of citrullinated antigens and the immunomodulatory host defence peptide LL-37. Vitamin D regulates LL-37 expression. This study assessed the associations of LL-37 and anti-CCP, vitamin D metabolites and vitamin D receptor (VDR) polymorphisms in early inflammatory arthritis (EIA). Methods Serum LL-37, 25-hydroxy-vitamin D (25OHvitD) and anti-CCP were measured by ELISA in treatment naïve EIA (n = 181). VDR single nucleotide polymorphisms (Fok1, Bsm1, Apa1, Taq1, Cdx-2) and HLADRB1 shared epitope (SE) alleles were detected by DNA amplification. Associations were tested in multivariable models. Median (25%, 75%) or percentiles are reported. Results Participants (70 % female, age 56 [45, 66] years, disease activity score [DAS28ESR3var] 3.7 [2.8, 4.8], 41 % anti-CCP positive, 68 % RA) had low serum 25OHvitD; 20.5 nmol/L (13.9, 29.0). In multivariable models, controlling for age, sex, SE, smoking and vitamin D deficiency, LL37 level (top quartile) associated with anti-CCP seropositivity (OR 22; 95% CI 4 to 104). Conclusions Levels of circulating LL-37 are associated with anti-CCP seropositivity. LL37 activity may be one mechanism linking infection and toxin exposure to anti-CCP generation.
Author Hitchon, Carol A
Meng, Xiaobo
El Gabalawy, Hani S
Larcombe, Linda
AuthorAffiliation University of Manitoba College of Medicine , Winnipeg , Manitoba , Canada
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  email: Carol.Hitchon@umanitoba.ca
  organization: University of Manitoba College of Medicine, Winnipeg, Manitoba, Canada
– sequence: 2
  givenname: Xiaobo
  surname: Meng
  fullname: Meng, Xiaobo
  organization: University of Manitoba College of Medicine, Winnipeg, Manitoba, Canada
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  givenname: Hani S
  surname: El Gabalawy
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  organization: University of Manitoba College of Medicine, Winnipeg, Manitoba, Canada
– sequence: 4
  givenname: Linda
  surname: Larcombe
  fullname: Larcombe, Linda
  organization: University of Manitoba College of Medicine, Winnipeg, Manitoba, Canada
BackLink https://www.ncbi.nlm.nih.gov/pubmed/31245047$$D View this record in MEDLINE/PubMed
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Issue 1
Keywords inflammation
ant-CCP
early rheumatoid arthritis
Language English
License This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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SSID ssj0001433713
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Snippet ObjectiveAntibodies to citrullinated peptides (anti-CCP) develop in individuals predisposed to rheumatoid arthritis (RA). Neutrophil extracellular traps are a...
Antibodies to citrullinated peptides (anti-CCP) develop in individuals predisposed to rheumatoid arthritis (RA). Neutrophil extracellular traps are a major...
Objective Antibodies to citrullinated peptides (anti-CCP) develop in individuals predisposed to rheumatoid arthritis (RA). Neutrophil extracellular traps are a...
Objective Antibodies to citrullinated peptides (anti-CCP) develop in individuals predisposed to rheumatoid arthritis (RA). Neutrophil extracellular traps are a...
SourceID doaj
pubmedcentral
proquest
crossref
pubmed
bmj
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
Publisher
StartPage e000874
SubjectTerms Age
Aged
ant-CCP
Anti-Citrullinated Protein Antibodies - blood
Anti-Citrullinated Protein Antibodies - immunology
Antibodies
Antimicrobial agents
Antimicrobial Cationic Peptides - blood
Antimicrobial Cationic Peptides - metabolism
Arthritis - blood
Arthritis - etiology
Arthritis - metabolism
Arthritis - pathology
Autoantibodies - blood
Autoantibodies - immunology
Autoimmunity
Biomarkers
Disease Susceptibility
Early Arthritis
early rheumatoid arthritis
Epitopes - genetics
Epitopes - immunology
Female
Females
Gene expression
Genetic Predisposition to Disease
Health risk assessment
Humans
Inflammation
Laboratories
Male
Middle Aged
Peptides
Polymorphism
Polymorphism, Single Nucleotide
Receptors, Calcitriol - genetics
Regression analysis
Rheumatism
Rheumatoid arthritis
Rheumatology
Severity of Illness Index
Smoking
Tuberculosis
Vitamin D
Vitamin deficiency
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Title Human host defence peptide LL37 and anti-cyclic citrullinated peptide antibody in early inflammatory arthritis
URI http://dx.doi.org/10.1136/rmdopen-2018-000874
https://www.ncbi.nlm.nih.gov/pubmed/31245047
https://www.proquest.com/docview/2216679265
https://www.proquest.com/docview/3109559581
https://search.proquest.com/docview/2248376988
https://pubmed.ncbi.nlm.nih.gov/PMC6560668
https://doaj.org/article/fbe51c5d81204e7092aa070e12c1e770
Volume 5
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