Systemic Sclerosis: Elevated Levels of Leukotrienes in Saliva and Plasma Are Associated with Vascular Manifestations and Nailfold Capillaroscopic Abnormalities.

Angélica Mandujano,Luis Humberto Silveira-Torre,Ignacio Méndez-Ramı́rez

doi:10.3390/ijerph182010841

Abstract

The role of leukotrienes (LTs) in the pathogenesis of systemic sclerosis (SSc) needs clarification. We analyzed the association of salivary (sa) and plasma (p) levels (pg/mL) of cysteinyl-leukotrienes (CysLT) and LTB4 with SSc vascular manifestations and nailfold capillaroscopy (NFC) in a cross-sectional study. Patients and healthy controls were evaluated for vascular manifestations and NFC. LTs were compared between groups as follows: SSc with or SSc without vascular features and controls, and by NFC parameters. Twenty SSc patients and 16 volunteers were recruited; Raynaud’s phenomenon (RP) history (SSc: saCysLT 99.4 ± 21.8 vs. controls: 23.05 ± 23.7, p = 0.01), RP at examination (SSc: saCysLT 129.3 ± 24.6 vs. controls: 23.05 ± 22.46, p = 0.01; pCysLT SSc: 87.5 ± 11.2 vs. controls: 32.37 ± 10.75, p = 0.002), capillary loss (saCysLT 138.6 ± 26.7 vs. 23.05 ± 21.6, p = 0.0007; saLTB4 3380.9 ± 426.6 vs. 1216.33 ± 346.1, p = 0.0005), “late” scleroderma pattern vs. controls (saCysLT 205.6 ± 32 vs. 23 ± 19.6, p = 0.0002; saLTB4 4564.9 ± 503.6 vs. 1216.3 ± 308.3; p < 0.0001) were all significant. Late patterns had higher levels (saCysLT, p = 0.002; LTB4 p = 0.0006) compared to active and early patterns (LTB4, p = 0.0006), and giant capillaries (p = 0.01) showed higher levels of LTs. Levels of pCysLT were higher in patients with RP at examination vs. patients without RP; saCysLT and LTB4 were higher in SSc group with vs. without capillary loss. LTs could be involved in the pathophysiology of vascular abnormalities. Further research is required to determine if blocking LTs could be a therapeutic target for SSc vascular manifestations.

Highlights

Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and some internal organs [1]
The cross-sectional study was conducted according to the guidelines of the Helsinki Declaration and local regulations, and we followed appropriate ethical research design and the relevant standards to ensure the protection of human subjects
We found higher levels of salivary and plasma CysLT in patients with Raynaud’s phenomenon (RP) and higher salivary levels of both LTB4 and CysLT were associated with loss of capillaries and “late” scleroderma pattern

Summary

Introduction

Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and some internal organs [1]. Vascular disease plays a central role in its pathogenesis. The pathogenesis involves the interaction of numerous biochemical mediators [1,6,7]; compared to others, leukotrienes (LTs) have received little attention. These lipidic molecules, including LTA4, LTB4 and cysteinyl-leukotrienes (LTC4, LTD4 and LTE4), are derived from arachidonic acid through the 5-lipoxygenase (5-LO) pathway and have both inflammatory and fibrotic properties [8,9,10,11]. LTs have been implicated in several animal and human models of fibrotic

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