You are here

Article Text

Article menu

Download PDFPDF

Early arthritis
Original article
Human host defence peptide LL37 and anti-cyclic citrullinated peptide antibody in early inflammatory arthritis
  1. Carol A Hitchon,
  2. Xiaobo Meng,
  3. Hani S El Gabalawy and
  4. Linda Larcombe
  1. University of Manitoba College of Medicine, Winnipeg, Manitoba, Canada
  1. Correspondence to Dr Carol A Hitchon; Carol.Hitchon{at}umanitoba.ca

Abstract

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.

  • early rheumatoid arthritis
  • inflammation
  • ant-CCP

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/.

https://doi.org/10.1136/rmdopen-2018-000874

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Footnotes

    • Contributors CAH, LL conceived and designed study. LL, XM conducted assays. CAH, HEG, LL interpreted data and drafted the manuscript. All authors approved final manuscript.

    • Funding Health Sciences Centre Foundation, Research Manitoba, Manitoba Medical Services Foundation, Canadian Arthritis Network. Canadian Institutes of Health Research (Institute of Musculoskeletal Heath and Arthritis, funding reference no. MOP-133409).

    • Competing interests Carol Hitchon has received unrelated research funds from Pfizer, UCB Canada.

    • Patient consent for publication All participants were enrolled with informed consent.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Select deidentified participant data only from consenting participants available from carol.hitchon@umanitoba.ca