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

• Published in: Rheumatic & 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
• Language: English
• Published: England EULAR 01.04.2019; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Original 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
• ISSN: 2056-5933; 2056-5933
• DOI: 10.1136/rmdopen-2018-000874

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.