Analysis of serum markers of cellular immune activation in patients with bullous pemphigoid

Abstract

Experimental models of bullous pemphigoid (BP), the most frequent subepidermal autoimmune bullous disease, revealed that the immune response leading to blister formation represents an incompletely understood complex process involving different inflammatory cells. In contrast to previous reports commonly focusing on limited molecular and cellular phenotypes of the disease, the aim of this study was to investigate a broad spectrum of markers of cellular immune activation in patients with BP. We found that serum levels of soluble CD4, myeloperoxidase, S100A12, eosinophil cationic protein and soluble P-selectin were significantly elevated in patients with active BP compared with normal controls. Mast cell tryptase and neopterin serum levels significantly decreased at the time of clinical remission of the patients. Additionally, serum concentrations of soluble IL-2 receptor, mast cell tryptase and soluble P-selectin were significantly associated with levels of circulating anti-BP180 autoantibodies. Our findings confirm and extend previous reports suggesting some concomitant involvement of a panel of molecules representative for a wide spectrum of cellular players (T cells, mast cells, neutrophils, eosinophils, macrophages and platelets) orchestrating the inflammatory reaction in BP. These data may favour the employment of broad-spectrum or combined immunosuppressants, potentially together with an anticoagulant treatment, over cell- or molecule-specific targeted therapy in patients with this disorder.

Variation of the epidermal expression of glucocorticoid receptor‐beta as potential predictive marker of bullous pemphigoid outcome

“…This induced steroid insensitivity was previously demonstrated for chronically stimulated cells with pro‐inflammatory factors such as TNF‐α and IFN‐γ, two Th1 cytokine with elevated concentration in the blister fluid . More recently, both IL‐17 and IL‐23 were shown to increase the expression of GRβ in PBMC, which release soluble marker of immune activation . In this line, we recently demonstrated that IL‐17 and IL‐23 concentrations were elevated in the blister fluids of patients with BP and that sustained elevated concentrations of these cytokines in those patients were predictive of poor outcome .…”

Review of autoimmune blistering diseases: the Pemphigoid diseases

“…Pro‐Inflammatory cytokines such as IL‐17 and the related cytokines including IL‐13 and IL‐22 play a role in the recruitment of neutrophil and eosinophils, with elevated levels correlating with relapse of disease. Other parts of the cellular immune system such as mast cells, complement, neutrophils, macrophages, T cells, and eosinophils are thought to be involved in the pathophysiology . The majority of cases are not associated with an identifiable trigger .…”

“…Other parts of the cellular immune system such as mast cells, complement, neutrophils, macrophages, T cells, and eosinophils are thought to be involved in the pathophysiology. 18 The majority of cases are not associated with an identifiable trigger. 10 Drugs reported to trigger BP include diuretics (eg.…”

Mast cells drive IgE-mediated disease but might be bystanders in many other inflammatory and neoplastic conditions

“…160,162 Furthermore, a correlation of tryptase serum levels with disease activity was reported. 163 Interestingly, in addition to IgG, also IgE autoantibodies with the same or similar specificity are present in about 70% to 90% of patients with BP. 23,164 These findings suggest that MCs could be activated by FcεRI cross-linking by IgE-BP180 complexes.…”