Chiharu Tateishi

Anti-desmocollin autoantibodies in nonclassical pemphigus.

Despite the established pathogenic role of anti‐desmoglein (Dsg) antibodies in classical pemphigus, the significance of autoantibodies to another desmosomal cadherin, desmocollin (Dsc) is at present unknown. No consistent immunoassay for immunoglobulin (Ig) G autoantibodies to Dscs has been developed.

Coexistence of autoimmune bullous diseases (AIBDs) and psoriasis: A series of 145 cases

BACKGROUND Many case reports have described the coexistence of autoimmune bullous diseases (AIBDs) and psoriasis. Among them, anti-laminin γ1 (p200) pemphigoid is the best known. OBJECTIVES We sought to characterize patients with AIBDs and psoriasis and to investigate common AIBDs occurring in these patients. METHODS This retrospective study included 145 patients with coexisting AIBD and psoriasis given a diagnosis from January 1, 1996, to July 31, 2013, at an academic dermatology department. Of these, 134 were consultation cases regarding AIBD diagnosis. RESULTS Ratio of male to female patients was 5.7:1. Psoriasis onset preceded AIBD onset in most patients. Mean age at AIBD onset was 65.4 years, and mean duration between psoriasis and AIBD onset was 14.6 years. Most cases had single AIBD, whereas 16 cases had combined AIBDs. Bullous pemphigoid was the most prevalent (63.4%) followed by anti-laminin γ1 pemphigoid (37.2%). LIMITATIONS Consultation cases may not have included mild AIBD cases. CONCLUSION This study confirmed the association of psoriasis and anti-laminin γ1 pemphigoid. However, because bullous pemphigoid is a much more common disease, it is seen more frequently in patients with psoriasis than anti-laminin γ1 pemphigoid.

Pemphigoid with antibodies to laminin γ1, BP180 and BP230, associated with psoriasis vulgaris: Successful disease control with cyclosporin

Both anti‐laminin γ1 pemphigoid and bullous pemphigoid are autoimmune subepidermal blistering diseases. The former is rare and characterized by autoantibodies to laminin γ1, a 200‐kDa dermal protein, while the latter is common among the elderly and characterized by autoantibodies to BP180 and BP230, both of which are hemidesmosomal proteins. We experienced a 69‐year‐old Japanese male patient with blister formation secondary to erythrodermic psoriasis, which was successfully treated with cyclosporin. The histopathology of erythema corresponded with psoriasis and that of a blistering lesion showed infiltration of neutrophils and eosinophils in and around the subepidermal blisters. Patient immunoglobulin G antibodies labeled both the epidermal and dermal sides of 1 mol/L NaCl‐split human skin by indirect immunofluorescent microscopy and recognized laminin γ1, BP180 and BP230 by immunoblotting. To the best of our knowledge, this is the first report of coexistence of psoriasis and atypical pemphigoid with these three autoantibodies.

Three Cases of Linear IgA/IgG Bullous Dermatosis Showing IgA and IgG Reactivity With Multiple Antigens, Particularly Laminin-332

IMPORTANCE Linear IgA/IgG bullous dermatosis (LAGBD) is a relatively rare autoimmune bullous disease characterized by both IgA and IgG antibodies to epidermal basement membrane zone. The heterogeneity and pathogenesis of the LAGBD autoantigens have not been fully elucidated. OBSERVATIONS We report 3 Japanese cases of LAGBD (ages 81, 88, and 64 years; 1 woman and 2 men). The patients showed bullous and erosive lesions on the trunk and extremities with minimal mucosal lesions. Histopathological analysis revealed a subepidermal blister with neutrophilic infiltration with eosinophils in 2 cases. Direct and indirect immunofluorescence studies disclosed IgG and IgA antibasement membrane zone antibodies. In immunoblot analyses of various antigen sources, all cases showed IgG and IgA antibodies to various subunits of laminin-332, in addition to IgG and IgA reactivity with type VII collagen, laminin-γ1, and BP230 and BP180 recombinant proteins. CONCLUSIONS AND RELEVANCE Our studies revealed that the 3 LAGBD cases showed prominent IgG and IgA reactivity with laminin-332, which was only rarely reported. In addition, all cases showed IgG and IgA reactivity with other multiple antigens, indicating the role of epitope-spreading mechanisms initiated from laminin-332. The significance of IgA antibodies to laminin-332 should be studied in larger cohorts of both LAGBD and linear IgA bullous dermatosis.

Contact urticaria caused by a fish-derived elastin-containing cosmetic cream

A 26-year-old woman had experienced a number of episodes of fish allergy since she was 2 years of age. The patient developed respiratory distress and widespread wheals within 15 min after eating fish. Upon inhalation of smoke from grilled fish, she noticed discomfort in the oral cavity, with respiratory distress. She had strictly avoided eating fish. At the age of 20 years, however, when she drank a fish collagen-containing beverage, she had oropharyngeal irritation, rhinorrhoea, and facial angioedema, followed by widespread uriticaria and respiratory distress. When she was 24 years of age, an urticarial eruption occurred on the site where a cosmetic cream containing codfish-derived elastin was applied (Fig. 1a). Her past history included atopic dermatitis, bronchial asthma, allergic rhinitis, and egg allergy in childhood. Her serum total IgE level was 442 kU/l (normal, <170 kU/l). The radioallergosorbent test scores (maximum, class 6) for specific IgE were as follows: tuna, 6; salmon, 6; mackerel, 5; flatfish, 5; codfish, 4; horse mackerel, 4;

A successful treatment with ustekinumab in a case of antilaminin-γ1 pemphigoid associated with psoriasis.

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Laminin-511, inducer of hair growth, is down-regulated and its suppressor in hair growth, laminin-332 up-regulated in chemotherapy-induced alopecia

BACKGROUND Chemotherapy-induced alopecia (CIA) has a devastating cosmetic effect, especially in the young. Recent data indicate that two major basement membrane components (laminin-332 and -511) of the skin have opposing effects on hair growth. OBJECTIVE In this study, we examined the role and localization of laminin-332 and -511 in CIA. METHODS We examined the expression of laminin-332 and -511 during the dystrophic catagen form of CIA induced in C57BL/6 mice by cyclophosphamide (CYP) treatment. RESULTS Our data indicate that both laminin-332 and its receptor alpha 6 beta 4 integrin are up-regulated (both quantitatively and spatially) after mid to late dystrophic catagen around the outer root sheath (ORS) in the lower third of hair follicles in CIA. This up-regulation also occurs at the transcriptional level. In contrast, laminin-511 is down-regulated after mid dystrophic catagen at the protein level, with transcriptional inactivation of laminin-511 occurring transiently at the early dystrophic catagen stage in both epidermal and ORS keratinocytes. Laminin-511 expression correlates with expression of alpha 3 integrin in CIA and we also demonstrate that laminin-511 can up-regulate the activity of the alpha 3 integrin promoter in cultured keratinocytes. Injection of a laminin-511 rich protein extract, but not recombinant laminin-332, in the back skin of mice delays hair loss in CYP-induced CIA. CONCLUSIONS We propose that abrupt hair loss in CIA is, at least in part, caused by down-regulation of laminin-511 and up-regulation of laminin-332 at the transcriptional and translational levels.

Case of subepidermal autoimmune bullous disease with psoriasis vulgaris reacting to both BP180 C-terminal domain and laminin gamma-1.

A number of cases of psoriasis vulgaris developing bullous skin lesions have been diagnosed as either bullous pemphigoid with antibodies to the 180‐kDa bullous pemphigoid antigen (BP180) non‐collagenous 16a (NC16a) domain or anti‐laminin‐γ1 (p200) pemphigoid. We report a case of subepidermal bullous disease with psoriasis vulgaris, showing antibodies to both BP180 C‐terminal domain and laminin‐γ1. A 64‐year‐old Japanese man with psoriasis vulgaris developed exudative erythemas and tense bullae on the whole body but he did not have mucosal involvement. The blistering lesion showed subepidermal blisters histopathologically. In indirect immunofluorescence of 1 mol/L NaCl‐split skin, immunoglobulin (Ig)G antibodies reacted with both the epidermal and dermal side. Immunoblotting showed positive IgG with recombinant protein of BP180 C‐terminal domain and 200‐kDa laminin‐γ1 in normal human dermal extract.

Linear IgA/IgG bullous dermatosis reacts with multiple laminins and integrins

BackgroundSince the original description by Zone et al in 1994, the disease entity and target antigens in linear IgA/IgG bullous dermatosis (LAGBD) have not been clarified in 20 years.ObjectivesTo determine autoantibodies and autoantigens in a new LAGBD case which showed atypical clinical and histopathological findings without apparent mucosal involvement.Materials and MethodsWe performed various indirect immunofluorescence and immunoblotting studies.ResultsIndirect immunofluorescence of 1M NaCl-split skin showed IgG and IgA reactivity with both epidermal and dermal sides. Immunoblotting studies using various antigen sources revealed circulating IgG and IgA antibodies reactive with laminin-332, laminin-γ1 and integrin α6β4 in various patterns. Absorption study using recombinant proteins of laminin-γ1 indicated that the patient serum reacted with different epitopes between laminin-γ1 and laminin-γ2.ConclusionsThis study presented for the first time a LAGBD patient with IgG and IgA antibodies to various laminins and integrins.

Case of anti-laminin gamma-1 pemphigoid with antibody against C-terminal domain of BP180 in a patient with psoriasis vulgaris

against each component of BMZ (Fig. 1d). IgA and laminin-332 were detected on the dermal and epidermal sides of the blister, respectively (Fig. 1e). Type 4 (Fig. 1f) and type 7 collagen (Fig. 1g) were detected above the IgA deposit and on the dermal side of the blister. IgA deposits were observed above the elastic fibers (Fig. 1h). We diagnosed this case as DH, and DDS (75 mg/day) was started. The skin lesions improved and DDS was decreased to 25 mg/day with a favorable course. Immunomapping findings of DH have been described in two previous reports. Our study clearly showed that the level of cleavage was between type 7 collagen and laminin-332 in this case, similar to in epidermolysis bullosa acquisita and different from bullous pemphigoid, as demonstrated in our previous study. The vesicles of DH are recognized to develop in the lamina lucida based on the previous studies. Klein et al. studied seven DH patients and laminin was found on the floor of vesicles in five patients, while on the roof of vesicles in two patients. Smith et al. studied six biopsies, and laminin was found on the floor of the vesicle in three biopsies, while both on the floor and on the roof in one biopsy, and no staining in two biopsies. They speculated that the poor staining was attributed to destruction of laminin by the blistering process. These results suggest that the staining with anti-laminin antibody provides several different patterns in different patients, and that it may be difficult to conclude the cleavage site only from one patient. Laminin-332 on the floor of the bulla in our case might have been destructed, so that only laminin332 on the roof was detected, as suggested by Smith et al. However, we could also speculate that the difference in the staining pattern may be due to the difference in antibodies used, or to the difference in ethnic groups as suggested in the literature. Further immunomapping studies will be necessary to verify our speculation.