Proinflammatory Cytokines and Antiskin Autoantibodies in Patients With Inherited Epidermolysis Bullosa

Abstract

Epidermolysis bullosa (EB) is a rare disorder characterized by inherited skin adhesion defects with abnormal disruption of the epidermal–dermal junction in response to mechanical trauma. Our aim was to investigate a set of cytokine levels in serum samples from patients suffering from epidermolysis bullosa simplex (EBS), dystrophic epidermolysis bullosa (DEB), and healthy controls (HCs), exploring their potential correlations with antiskin autoantibody titers and disease activity. Forty patients afferent to the Dermatological Ward of Bari City Hospital and 9 HCs were enrolled and subdivided according to the dystrophic (DEB) and simplex forms (EBS). We found a significant increase in interleukin (IL)-1β plasmatic levels of DEB (P = 0.0224) and EBS (P = 0.0465) patients compared to HCs; IL-6 levels were significantly higher in DEB than in EBS patients (P = 0.0004) or HCs (P = 0.0474); IL-2 levels were significantly increased in DEB compared with EBS (P = 0.0428). Plasmatic tumor necrosis factor-β and interferon-γ were higher in DEB patients than in HCs (P = 0.0448 and 0.0229). Conversely, tumor necrosis factor-α was significantly decreased in DEB (P = 0.0034). IL-5 correlated with anti-BP180 (r = −0.5018, P = 0.0338), anti-BP230 (r = −0.6097, P = 0.0122), and anticollagen VII (r = −0.5166, P = 0.0405) autoantibodies; interferon-γ correlated with anti-BP180 (r = 0.9633, P < 0.0001), anti-BP230 (r = 0.9071, P < 0.0001), and anticollagen VII (r = 0.8619, P = 0.0045) autoantibodies. Score of disease severity was significantly correlated with IL-6 (r = 0.6941, P = 0.029) and IL-12 (r = 0.5503, P = 0.0272). The present study supports that EB might be considered a systemic inflammatory disease rather than a skin-limited disorder; clinical disease activity scores could be also integrated by laboratory data such as IL-6 and IL-12 dosage; biotherapies targeting specific cytokine networks probably represent a way to go in the future.

Autoimmunity and Cytokine Imbalance in Inherited Epidermolysis Bullosa

“…In agreement with the results of the study by Annichiarico et al [13] but in contrast with the data published several years ago by Chopra et al [29,30], an increase in the IL-2 serum concentration in EB cases regardless of disease severity was shown in this study. IL-2 signaling is essential for the development, function and homeostasis of regulatory T cells, and increased levels of this cytokine have been shown in skin diseases, such as psoriasis [31].…”

“…First, some cases of EB are complicated by autoimmune extracutaneous diseases [6,7,8,9,10,11]. Moreover, in several patients with EB, high levels of anti-skin antibodies, proportional to the severity of the disease, could be found [12,13]. Finally, a significant cytokine imbalance was demonstrated in EB, suggesting the presence of a systemic inflammatory disorder [13].…”

“…Moreover, in several patients with EB, high levels of anti-skin antibodies, proportional to the severity of the disease, could be found [12,13]. Finally, a significant cytokine imbalance was demonstrated in EB, suggesting the presence of a systemic inflammatory disorder [13]. All of these findings seem to indicate that EB is a systemic disorder in which several factors play a role in determining the development and severity of the different EB types.…”

Pro-Inflammatory Chemokines and Cytokines Dominate the Blister Fluid Molecular Signature in Patients with Epidermolysis Bullosa and Affect Leukocyte and Stem Cell Migration

“…Elevated levels of cytokines such as IL-1β, IL-2, IL-6 and reduced levels of TNFα have been reported in the serum of DEB and EBS patients, suggesting that EB could be classified as a systemic inflammatory disease rather than a skin-limited disorder (Annicchiarico et al, 2015). Cytokine antibody array analysis showed that BF of all EB types share a similar profile: out of 88 examined cytokines, adiponectin (ACRP30), angiogenin and IL-6 were detected at the highest levels (Fig.…”

“…Increased levels of CCL2, CCL19 and CCL20 were observed in the skin of EBS mice (Annicchiarico et al, 2015, Heinemann et al, 2011, Lettner et al, 2013, Roth et al, 2009). Our prior studies also identified reduced transcription of CCl27, CSF3, CX3CL1 and CXCL14 and higher expression of CXCL18 in the non-blistering skin of JEB and DEB transgenic mice (Alexeev et al, 2013).…”