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Abstract Number: 1362

Associations Between 25-Hydroxyvitamin D, Parathyroid Hormone, and Cathelicidin Concentrations with Inflammation and Cardiovascular Risk in Subjects with Pediatric Systemic Lupus Erythematosus

Varsha Gupta1, Vin Tangpricha2, Eric Yow3, Grace McComsey4, Laura E. Schanberg5, Angela B. Robinson6 and APPLE Investigators Group, 1Case Western Reserve University School of Medicine, Cleveland, OH, 2Medicine, Emory University School of Medicine, Atlanta, GA, 3Biostatistics, Duke Clinical Research Institute, Durham, NC, 4Pediatric Infectious Diseases, Rheumatology, and Geographic Medicine, Rainbow Babies and Children's Hospital / Case Medical Center, Cleveland, OH, 5Department of Pediatrics, Duke University Medical Center, Durham, NC, 6Pediatric Rheumatology, Rainbow Babies and Childrens Hospital, Cleveland, OH

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Clinical research, Lupus, parathyroid hormone and pediatrics, Vitamin D

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Session Information

Date: Monday, November 14, 2016

Title: Pediatric Rheumatology – Clinical and Therapeutic Aspects - Poster II: Myositis, Systemic Lupus Erythematosus, Sjögren's Syndrome

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Previous studies have shown associations between reduced serum 25-hydroxyvitamin D (25OHD) levels, inflammation, and disease activity in pediatric systemic lupus erythematosus (pSLE). The goal of this study was to assess the role of parathyroid hormone (PTH) in its relationship with vitamin D and inflammation, and to better understand the role of human cathelicidin (LL-37) in pSLE. LL-37 is upregulated by activated vitamin D and has antimicrobial and immunomodulatory properties. We examined the relationship between 25OHD and LL-37 concentrations to determine whether LL-37 concentrations are associated with the chronic inflammation seen in pSLE.

Methods: Available frozen serum samples from the 3-year APPLE study (n=221 participants) were used to determine 25OHD, PTH, and LL-37 levels at study entry. Pearson’s correlations and Chi-square 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 study.

Results: 201/221 APPLE participants had serum available for analysis. 61/201 had vitamin D deficiency at baseline. Serum 25OHD was inversely associated with PTH, r = -0.39 (p < 0.01), but not with LL-37 (p = 0.58). LL-37 levels ranged from 18.3 to 289.2 ng/mL, with a mean level of 57.2 (SD 30.6) ng/mL. PTH was not associated with hsCRP, carotid IMT, or HDL- or LDL-cholesterol, but was negatively associated with lipoprotein(a) levels, r = -0.15 (p = 0.03). Despite no association with serum 25OHD, LL-37 was negatively associated with total cholesterol, HDL- and LDL-cholesterol, and positively associated with age (Table 1). There was no significant difference in mean LL-37 levels in participants with reported infection as an adverse event during the 3 years of study.

Conclusion: As expected, PTH was negatively associated with 25OHD, but interestingly, LL-37 levels were not associated with 25OHD. Serum levels may not reflect the interaction of 25OHD and LL-37 at a cellular level. Notably, many LL-37 levels were significantly elevated over normal. There may be an association between LL-37 and cardiovascular risk (via cholesterol). These exploratory results addressing the role of LL-37 levels in pSLE inflammation and infection appear worthy of future study. Table 1:

Variable 1 Variable 2 Pearson correlation coefficient P-Value
25OHD (ng/mL) LL-37 (ng/mL) Baseline 0.04 0.58
25OHD (ng/mL) PTH (pg/mL) Baseline -0.39 <0.01
LL-37 (ng/mL) PTH (pg/mL) Baseline 0.07 0.30
PTH (pg/mL) Age at Randomization (Years) -0.10 0.14
PTH (pg/mL) Body Mass Index (kg/m*m) 0.04 0.60
PTH (pg/mL) SLEDAI Total -0.01 0.93
PTH (pg/mL) Mean-Mean IMT Common (mm) 0.01 0.84
PTH (pg/mL) Total Cholesterol (mg/dL) -0.13 0.06
PTH (pg/mL) Triglycerides (mg/dL) 0.01 0.99
PTH (pg/mL) HDL Cholesterol (mg/dL) -0.11 0.11
PTH (pg/mL) LDL Cholesterol (mg/dL) -0.11 0.13
PTH (pg/mL) Lp(a) (mg/dL) -0.12 0.03
PTH (pg/mL) Homocysteine Level (mcmol/L) 0.01 0.90
PTH (pg/mL) High Sensitivity CRP (mg/L) 0.03 0.65
Log of LL-37 (ng/mL) Age at Randomization (Years) 0.15 0.03
Log of LL-37 (ng/mL) Body Mass Index (kg/m*m) 0.10 0.16
Log of LL-37 (ng/mL) SLEDAI Total -0.14 0.06
Log of LL-37 (ng/mL) Mean-Mean IMT Common (mm) 0.01 0.98
Log of LL-37 (ng/mL) Total Cholesterol (mg/dL) -0.22 <0.01
Log of LL-37 (ng/mL) Triglycerides (mg/dL) -0.02 0.82
Log of LL-37 (ng/mL) HDL Cholesterol (mg/dL) -0.19 <0.01
Log of LL-37 (ng/mL) LDL Cholesterol (mg/dL) -0.19 <0.01
Log of LL-37 (ng/mL) Lp(a) (mg/dL) 0.02 0.83
Log of LL-37 (ng/mL) Homocysteine Level (mcmol/L) -0.13 0.08
Log of LL-37 (ng/mL) High Sensitivity CRP (mg/L) -0.02 0.76

Disclosure: V. Gupta, None; V. Tangpricha, None; E. Yow, None; G. McComsey, None; L. E. Schanberg, Sobi, UCB, Sanofi, 5; A. B. Robinson, None.

To cite this abstract in AMA style:

Gupta V, Tangpricha V, Yow E, McComsey G, Schanberg LE, Robinson AB. Associations Between 25-Hydroxyvitamin D, Parathyroid Hormone, and Cathelicidin Concentrations with Inflammation and Cardiovascular Risk in Subjects with Pediatric Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/associations-between-25-hydroxyvitamin-d-parathyroid-hormone-and-cathelicidin-concentrations-with-inflammation-and-cardiovascular-risk-in-subjects-with-pediatric-systemic-lupus-erythematosus/. Accessed .
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