Increased tryptase and myeloperoxidase levels in blister fluids of patients with bullous pemphigoid: correlations with cytokines, adhesion molecules and anti‐basement membrane zone antibodies

Abstract

Tryptase and myeloperoxidase respectively represent 2 specific markers of activated mast cells or neutrophils. Therefore, establishing the levels of these enzymes may be useful to quantify the cell involvement in the tissues or fluids of different origins and in different pathologies. The aim of this study was to analyse the levels of these 2 markers in both the sera and blister fluids of patients affected with bullous pemphigoid. These levels were then correlated to the concentrations of 19 cytokines and 2 soluble adhesion molecules determined in the same samples and also with the log (anti-basement membrane zone antibody) titres, evaluated in the patients' sera. For these purposes, 15 patients with bullous pemphigoid (10 males and 5 females; median age: 84 years, range 66-87; median disease duration: 0 years, range 0-3: median number of skin lesions: 17, range 14-30; median anti-basement membrane zone antibody titre: 1:320, range 0.0-1:2560) and 15 normal subjects (11 males and 4 females, median age: 81 years, range 59-86) were analysed by means of commercially available kits. Results showed that blister fluid myeloperoxidase and tryptase levels were increased as compared with the respective sera (P<0.01) and several correlations were observed with cytokines and adhesion molecules. In fact, significant correlations of blister fluid tryptase levels were observed with IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, VEGF, RANTES and sICAM-1, while myeloperoxidase was correlated with IL-1beta, IL-13 and IL-15. The blister fluid tryptase levels were also significantly correlated with the anti-basement membrane zone antibody titres (R=0.53, P=0.05). In conclusion, these findings are in accord with an involvement of both mast cells and neutrophils in bullous pemphigoid and their recruitment may be mediated by different biological modulators. Our findings seem to indicate that the cytokine (IL-3, IFN-gamma and OSM) or adhesion molecule (sICAM-1) concentrations in blister fluid are logarithmically related to the anti-basement membrane zone antibody titers.

Serum Eosinophil Cationic Protein, Myeloperoxidase, Tryptase, Eotaxin and Th2-Like Cytokines in Dermatitis herpetiformis

“…Increased MPO and TRY levels detected in blister fluids of patients with BP support the hypothesis of an involvement of both neutrophils and mast cells in the pathogenesis of the disease [13]; significant differences have been evidenced in the concentrations of these markers in blister fluid and serum, especially for TRY levels that were always undetectable in the sera [13], in agreement with our findings.…”

“…This specific proteolytic enzyme has been found to be elevated in serum during acute anaphylaxis [12]and in blister fluid of subjects with bullous pemphigoid (BP) [13]. Furthermore, significant alterations in mast cell chymase and protease inhibitors have been documented in other bullous diseases, such as DH and linear IgA dermatosis [14].…”

Heparin modulates the growth and adherence and augments the growth‐inhibitory action of TNF‐α on cultured human keratinocytes

“…The potentiating effect of heparin in high-calcium culture seems to be specific for this sulphated glycosaminoglycan since we have not found any similar effect when using hyaluronic acid with TNF-a under similar culture conditions (unpublished results). The possible relation of the present finding to the poor reepithelialization of chronic ulcers or blister bases is of interest since, for example, in blister fluids of pemphigoid elevated levels of tryptase, histamine and TNF-a have been measured [Katayama et al, 1984;Rhodes et al, 1999;D'Auria et al, 2000]. The results suggest that in addition to the cell cycle arrest at G0/G1 phase also the migration and adherence are simultaneously affected resulting in poor keratinocyte growth by the heparin-TNF-a mixture.…”

“…However, the number of mast cells is increased in the papillary dermis and in contact with the epidermis in chronic inflammatory skin diseases and in leg ulcers [Green et al, 1977;Bolton and Montagna, 1993;Huttunen et al, 2000]. In addition, mast cells have been linked to skin diseases leading to dermal-epidermal separation and blister formation [Briggaman et al, 1984;Kaminska et al, 1999a,b;D'Auria et al, 2000]. Therefore, mast cells and their mediators are assumed to be involved in the epithelialization of chronic wounds and blister bases.…”

A gene network bioinformatics analysis for pemphigoid autoimmune blistering diseases

“…In pemphigoid diseases, the release of some proteolytic enzymes, involved in blistering formation, was highly correlated with a set of immunoregulatory cytokines [31]; high levels of IL-4, IL-5, IL-10, IL-13, IL-17 and IFN-γ have been detected in skin lesions or sera of patients with bullous pemphigoid and especially regarding IL-4 and IL-13 for ocular cicatricial pemphigoid and for oral mucous membrane pemphigoid, confirming their presumed involvement in the cicatricial scarring process [32][33][34]. IL-13 promoted both fibroblast migration and up-regulation of the expression for major histocompatibility complex components (HLA) and for some CD proteins, so that fibroblasts may perpetuate chronic inflammation and continue fibrosis [33].…”