Analysis of relationships between 25-hydroxyvitamin D, parathyroid hormone and cathelicidin with inflammation and cardiovascular risk in subjects with paediatric systemic lupus erythematosus: An Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) study

• Type of Material: Article
• Authors: Varsha Gupta, Case Western Reserve University School of Medicine; Vin Tangpricha, Emory University; Eric Yow, Duke Clinical Research Institute; Grace A. McComsey, Case Medical Center; Laura Schanberg, Duke University Medical Center; Angela Byun Robinson, Rainbow Babies and Children’s Hospital/ Case Medical Center
• Language: English
• Date: 2018-01-01
• Publisher: BMJ Publishing Group: Open Access
• Publication Version: Final Published Version
• Copyright Statement: © 2018 Article author(s) (or their employer(s) unless otherwise stated in the text of the article). All rights reserved.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1136/lupus-2017-000255
• Title of Journal or Parent Work: Lupus Science & Medicine
• ISSN: 2053-8790
• Volume: 5
• Issue: 1
• Start Page: e000255
• End Page: e000255
• Grant/Funding Information: Secondary analysis supported by the Rainbow Babies and Children’s Hospital Pediatrics Pilot Award and the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases contract 5P30-AR-047363-12).; APPLE supported by the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases contract N01-AR-2-2265), the Edna and Fred L Mandel Jr. Center for Hypertension and Atherosclerosis and Pfizer.
• Keywords: systemic lupus erythematosus; infections; inflammation; Childhood/paediatric lupus; autoimmune diseases
• Research Categories: Health Sciences, General; Health Sciences, Human Development

Abstract

Objectives Previous studies demonstrated associations between reduced serum 25-hydroxyvitamin D (25OHD), inflammation and disease activity in paediatric systemic lupus erythematosus (pSLE). The goal of this study was to assess parathyroid hormone (PTH) in its relationship to vitamin D and inflammation, as well as to better understand the role of human cathelicidin (LL-37) in pSLE. Methods Frozen serum samples collected at baseline of the Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) study were assayed to determine 25OHD, PTH and LL-37 levels. Pearson's correlations and Χ 2 tests were used to evaluate the relationships between 25OHD, PTH, LL-37, inflammation, disease activity and infection using baseline values collected as part of the APPLE study. Results 201/221 APPLE participants had serum available for analysis. Serum 25OHD was inversely associated with serum PTH, but not LL-37. Serum PTH was not associated with high sensitivity C-reactive protein, carotid intima media thickness or high-density lipoprotein (HDL) or low-density lipoprotein (LDL) cholesterol, but was negatively associated with lipoprotein(a) levels. Despite no association with serum 25OHD, LL-37 was negatively associated with total cholesterol, HDL and LDL cholesterol and positively associated with age. There was no significant difference in mean LL-37 levels in participants with reported infection as an adverse event during the 3-year APPLE study. Conclusions Despite links to vitamin D levels in other studies, LL-37 levels were not associated with baseline serum 25OHD concentrations in paediatric patients with pSLE. Despite the lack of correlation with 25OHD, LL-37 levels in this study were associated with cholesterol levels. Some subjects with pSLE have significantly elevated levels of LL-37 of unknown significance. These exploratory results addressing the role of LL-37 levels in pSLE appear worthy of future study.