Th2‐like cytokine activity in dermatitis herpetiformis

Caproni, Marzia; Feliciani, Claudio; Fuligni,; Salvatore, Giovanni A.; Atani,; Bianchi,; Pour, Mohammad; Proietto,; Toto,; Coscione,; Amerio, Paolo; Fabbri,

doi:10.1046/j.1365-2133.1998.02068.x

Cited by 53 publications

(47 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Main infiltrating cell populations in DR lesional skin are constituted by T lymphocytes and neutrophils (19). Although FasL expression was initially confined to activated T cells, recent studies indicated that FasL can be expressed by neutrophils and other cell types (24).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Role of Apoptosis in the Pathogenesis of Dermatitis Herpetiformis

Caproni

Torchia

Antiga

et al. 2005

Int J Immunopathol Pharmacol

View full text Add to dashboard Cite

Apoptosis is a form of cell death that is claimed to be involved in a number of chronic inflammatory and malignant skin diseases. The aim of this study was to investigate whether apoptosis may contribute to the pathogenesis of epidermal changes in dermatitis herpetiformis (DR) and, in particular, whether certain apoptosis-related markers such as Bax, Bcl-2, Fas and Fas ligand (FasL) take part in this process. For the detection of apoptotic nuclei, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling technique (TUNEL) was employed on cryostat sections. Skin lesions from six and perilesional skin from four DH patients were stained with monoclonal antibodies to Bax, Bcl-2, Fas and FasL. The same evaluation was also performed on three patients affected by bullous pemphigoid (BP) and in two healthy donors. Using TUNEL technique, a remarkable increase in the apoptotic rate within the epidermal compartment was observed in DH and BP patients in comparison with normal controls. In our immunohistochemical analysis, Bax/Bcl-2 ratio was almost the same in the epidermis of perilesional/lesional DH, BP and healthy skin specimens. In DH and BP specimens both Bax and Bcl-2 proteins were increased in the dermal perivascular compartment. Fas showed a prevalently epidermal staining, both in DH and BP lesions, while FasL was distributed in perivascular and subjunctional dermis; some FasL+ cells infiltrated the DEJ and the basal layer of epidermis. This study allowed us to highlight conspicuous apoptotic phenomena in basal and suprabasal keratinocytes within lesional and perilesional skin ofDH. We conclude that in DH, as well as in BP, apoptosis plays a role in the pathogenesis of cutaneous lesions in concert with other pathogenetic mechanisms.Dermatitis herpetiformis (DH) is an autoimmune subepidermal blistering disease characterized by chronic and recurrent eruptions of erythematous, urticarial, papular, vesicular and bullous lesions. Granular IgA deposits at the dermal papillae represent the immunological marker of the disease, that is strictly associated with a gluten-sensitive enteropathy (GSE), indistinguishable from coeliac disease (CD) (1). To date, immunopathological mechanisms that lead to blister formation in DH are only partially known. In this respect, granular IgA deposition at the dermo-epidermal junction (DEJ), neutrophils and eosinophils together with activated CD4+ Th2 lymphocytes are supposed to represent the main immune mechanisms involved in the pathogenesis of the disease (1-2).Apoptosis is a sequence of events based on cellular metabolism that lead to cell shrinkage,

show abstract

Section: Discussionmentioning

confidence: 99%

“…Polyclonal IgA 1 antibodies are detectable as junctional granular deposits in perilesional DH skin; they seem to be able to activate the complement cascade and subsequently to enhance neutrophil chemotaxis and cytokine elaboration. Some studies suggest that Th2 lymphocytes also play an important role in the DH immunoinflammation (19).…”

Section: Discussionmentioning

confidence: 99%

The Role of Apoptosis in the Pathogenesis of Dermatitis Herpetiformis

Caproni

Torchia

Antiga

et al. 2005

Int J Immunopathol Pharmacol

View full text Add to dashboard Cite

show abstract

“…Although both celiac disease and DH have elements of combined cellular and humoral responses, DH is generally considered to be predominantly a Th2-mediated disease and celiac disease to be a Th1-mediated disease (35)(36)(37). The intraperitoneal injections, which typically generate humoral responses, may therefore be contributing to the development of a humoral disease that is skewed toward a Th2 response.…”

Section: Discussionmentioning

confidence: 99%

A new model for dermatitis herpetiformis that uses HLA-DQ8 transgenic NOD mice

Marietta¹,

Black²,

Camilleri³

et al. 2004

J. Clin. Invest.

115

View full text Add to dashboard Cite

Dermatitis herpetiformis (DH) is an autoimmune blistering skin disorder that is associated with gluten sensitivity. It presents as a papulovesicular rash and is often associated with enteropathy. The rash resolves when the patient is placed on a gluten-free diet and/or dapsone. DH, as well as celiac disease, is tightly associated with DQ2 and DQ8. A novel mouse model for DH is described that utilizes the NOD background and the HLA-DQ8 transgene. The addition of DQ8 contributes sensitivity to gliadin, and the addition of the NOD background contributes to autoimmunity and pathogenesis. Fifteen NOD DQ8 + mice of 90 that were sensitized to gluten developed blistering pathology similar to that seen in DH. Neutrophil infiltration of the dermis, deposition of IgA at the dermal-epidermal junction, and a complete reversal of the blistering phenomenon with the administration of a gluten-free diet with or without dapsone were observed. None of the 3 blistering mice examined had small-bowel pathology. This animal model of DH will be useful to determine the specificity of the IgA deposits, as well as the pathogenic mechanisms that occur in the skin as a result of gluten ingestion.

show abstract

“…In addition, IL-4 and IL-13 mediate the production of eotaxin and modulate eosinophilic infiltration in immunological reactions (12). The T-cell-mediated immune response is thought to be associated with the pathogenesis of granular-type DH, because the CD4-positive T-cell infiltrated in the skin lesions of DH patients seems to act mainly through the production of Th2-type cytokines, such as IL-4, IL-5 and IL-13 (8). However, a significant increase in the serum levels of Th2-type cytokines was not observed in patients with granular-type DH (13).…”

Section: Discussionmentioning

confidence: 99%

“…Fibrillar-type DH appears to be rare in Caucasian populations (6). While the pathogenesis of DH is unclear, previous studies have suggested that the expression of interleukin (IL)-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and Th2-type cytokines could be important in the tissue infiltration process of eosinophils and neutrophils in granular-type DH (7,8). The present study investigated the levels of serum cytokines and chemokines in order to clarify their presence and activity in the pathogenesis of fibrillar-type DH.…”

mentioning

confidence: 99%

Increased Serum Levels of Th2-type Cytokines and Eotaxin in Fibrillar-type Dermatitis Herpetiformis

Makino

Yoshihisa²,

Mizawa³

et al. 2017

Acta Derm Venerol

View full text Add to dashboard Cite

Dermatitis herpetiformis (DH) is a pruritic papulovesicular disease that is symmetrically distributed over the shoulders, elbows, back and knees. Immunofluorescence has revealed granular IgA deposition in the papillary dermis. IgA antibodies to both epidermal transglutaminase (eTG) and tissue transglutaminase (tTG) are usually detected in patients with DH. DH is commonly thought to be a cutaneous manifestation of gluten-sensitive enteropathy (GSE) (1, 2). We refer to this condition as "granular-type DH". Although DH is a relatively common disease in Caucasian populations, it is rare in Japan. Most Japanese patients with DH show unique features, including a high frequency of fibrillar IgA deposition in the papillary dermis, rare occurrence of GSE, absence of the HLA-DQ2/DQ8 haplotype and rare associations with autoimmune disease and lymphoma, although the histological findings appear to be similar to those of granulartype DH (3, 4). Furthermore, as reported previously, these patients appear to have IgA antibodies to eTG, but not tTG (5). We refer to this condition as "fibrillar-type DH". The clinical and histological findings of typical fibrillar-type DH are shown in Fig. S1 1 . Fibrillar-type DH appears to be rare in Caucasian populations (6). While the pathogenesis of DH is unclear, previous studies have suggested that the expression of interleukin (IL)-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and Th2-type cytokines could be important in the tissue infiltration process of eosinophils and neutrophils in granular-type DH (7,8). The present study investigated the levels of serum cytokines and chemokines in order to clarify their presence and activity in the pathogenesis of fibrillar-type DH. MATERIALS AND METHODS (see Appendix S11 ) RESULTSThe study population included 5 patients with fibrillartype DH (mean age 67.4 years; age range 41-81 years) in the active stage of the disease, who had not received any treatment and in whom the development of new lesions had been observed ( Table I). The levels of IgA antibodies against eTG were markedly increased in all patients. However, no IgA antibodies against tTG were detected in any of the patients. None of the patient's intestinal tissue specimens showed villous atrophy or lymphocytic cell infiltration.The serum level of interferon (IFN)-γ, a Th1-like cytokine, was increased slightly in the patients with DH (mean 0.414 ± 0.23; range 0.21-0.80 pg/ml) in comparison with the control subjects; however, the difference was not statistically significant. IL-12, another Th1-like cytokine, was not detected in either the patients with DH or the control subjects (Fig. S2a 1 ). The patients' serum levels of Th2-like cytokines IL-4 (mean14.55 ± 5.3 pg/ml; range 6.84-21.71 pg/ml, p < 0.005), IL-5 (mean 6.09 ± 0.99 pg/ml; range 4.84-7.49 pg/ml, p < 0.001) and IL-13 (mean 1.14 ± 0.20 pg/ml; range 0.85-1.36 pg/ml, p < 0.005) were significantly increased in comparison with the normal subjects: IL-4: mean 0.04 ± 0.09 pg/ml; range 0-0.21 pg/ml, IL-5: mean 0.55 ± 0.14 p...

show abstract

Th2‐like cytokine activity in dermatitis herpetiformis

Cited by 53 publications

References 32 publications

The Role of Apoptosis in the Pathogenesis of Dermatitis Herpetiformis

The Role of Apoptosis in the Pathogenesis of Dermatitis Herpetiformis

A new model for dermatitis herpetiformis that uses HLA-DQ8 transgenic NOD mice

Increased Serum Levels of Th2-type Cytokines and Eotaxin in Fibrillar-type Dermatitis Herpetiformis

Contact Info

Product

Resources

About