Session Information
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 |
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 .« Back to 2016 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - 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/