The role of Vitamin D in immuno-inflammatory responses in Ankylosing Spondylitis patients with and without Acute Anterior Uveitis

Abstract

Hypothesis:Abnormal Vitamin D (Vit D) level could have consequences on the immuno-inflammatory processes in Ankylosing Spondylitis (AS). Aim:The purpose of this study was to analyze the role of Vitamin D in the interplay between immune and inflammation effectors in AS associated-Acute Anterior Uveitis (AAU). Methods and Results:25-hydroxyvitamin D (Vit D), LL-37 peptide, IL-8 and Serum Amyloid A (SAA) were identified and quantified in the serum/ plasma of thirty-four AS patients [eleven AS patients presenting AAU (AAU AS patients) and twenty-three AS patients without AAU (wAAU AS patients)] and eighteen healthy individuals (Control) using enzyme-linked immunosorbent assay. Acute-phase SAA level was significantly higher in AS patients compared to Controls. Contrary with wAAU AS patients, significantly elevated levels of IL-8, and diminished levels of Vit D characterized AAU AS patients. Regarding LL-37, its level decreased concomitantly with the level of Vit D. When AS patients were subgrouped based on AAU presence or on Vit D level, important associations between immuno-inflammatory assessed markers and AS features were noticed. Generally, Vit D levels were associated indirectly with leukocytes/ neutrophils number or with ESR, CRP, and Fibrinogen levels. The levels of SAA and IL-8 associated directly with AAU or with AAU relapses, especially in AS patients with Vit D insufficiency, while SAA associated directly with infection/ inflammatory markers and with disease activity indexes or with the degree of functional limitation. Discussion:Altered levels of Vit D affect the balance between LL-37, IL-8 and SAA, suggesting an association with AAU, an extra-articular manifestation of AS. Abbreviations:Vit D = Vitamin D, AS = Ankylosing Spondylitis, AAU = Acute Anterior Uveitis, AAU AS = AS patients with AAU, wAAU AS = AS patients without AAU, SSZ = Sulphasalazine, Leu = Leukocytes, Neu = Neutrophils.

Keywords: Ankylosing Spondylitis; IL-8; LL-37; SAA; Vitamin D.

Table 1

Table 1.Characterization of AS patients and Controls

Table. 2

Table 2Immuno-inflammatory assessed markers that differentiated between AAU AS and wAAU AS patients

Fig. 1

Fig. 1Vit D, LL-37, IL-8, and SAA levels in AS patients. Using commercial ELISA kits the levels of Vit D, LL-37, IL-8, and SAA were quantified in serum/ plasma of thirty-two AS patients. AS patients were distributed into subgroups based on AAU presence and the results for Vit D, LL-37, IL-8, and SAA levels are presented as dot plots. The concentrations of LL-37 and SAA in plasma samples were divided by 10 and 100, respectively. Mean values ± standard deviations (SD), calculated for each immuno-inflammatory assessed markers and each subgroup of AS patients, are included

Fig. 2

Fig. 2The distribution of immuno-inflammatory assessed markers depending on Vit D status in AS patients. AS patients were divided into subgroups based on serum Vit D level as it follows: AS patients with Vit D sufficiency (G1), AS patients with Vit D insufficiency (G2) and AS patients with Vit D deficiency (G3). The results for Vit D, LL-37, IL-8, and SAA levels quantified by ELISA are presented as dot plots. The concentrations of LL-37 and SAA in plasma samples were divided by 10 and 100, respectively. Mean values ± standard deviations (SD), calculated for each immuno-inflammatory assessed markers and each subgroup of AS patients, are included

Table 3.

Table 3Relationship between immuno-inflammatory assessed markers and clinical/ paraclinical AS features. The level of each immune/ inflammatory assessed marker was correlated with each established clinical and laboratory markers for AS by using Spearman’s rank nonparametric correlation test (two-tailed). Insignificant results (P >0.050) were not included

Table 4.

Table 4Relationship between Vit D and SAA and clinical/paraclinical AS features in AAU AS and wAAU AS patients. For each subgroup of AS patients (AAU AS and wAAU AS), the levels of immuno-inflammatory assessed markers were correlated with each established clinical and laboratory markers using Spearman’s rank nonparametric correlation test (two-tailed). Only significant results (P <0.050) were included.

Table 5.

Table 5Relationship between Vit D and SAA and clinical/paraclinical AS features in AAU AS and wAAU AS patients. For each subgroup of AS patients (AAU AS and wAAU AS), the levels of immuno-inflammatory assessed markers were correlated with each established clinical and laboratory markers using Spearman’s rank nonparametric correlation test (two-tailed). Only significant results (P <0.050) were included.