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Summary: We report a unique case of a Japanese woman with herpetiform pemphigus (HP) who had IgG autoantibodies reactive with nondesmosomal sites of keratinocytes and presented characteristic transmission electron microscopic (TEM) findings of various‐sized vacuoles in keratinocytes without acantholysis. The patient presented with pruritic annular oedematous erythemas with small blisters lining the margins on the trunk and extremities. Histopathological examinations showed intraepidermal blisters with prominent infiltrations of eosinophils. Direct and indirect immunofluorescence tests revealed the presence of in vivo bound and circulating IgG autoantibodies to the keratinocyte cell surfaces. However, enzyme‐linked immunosorbent assays for desmoglein (Dsg) 1, Dsg3 and desmocollins 1–3 showed negative results. Immunoblotting using the full‐length human Dsg1 recombinant protein showed a positive band. TEM examination showed various‐sized vacuoles squashing the nuclei in many keratinocytes, resulting in rupture of the cells. Immunoelectron microscopic examination revealed IgG deposition over the entire keratinocyte cell surfaces, which spared the desmosomes. IgG antibodies were also present on the inside walls of the vacuoles around the nuclei of keratinocytes and on the cell surfaces of infiltrating eosinophils. This patient also had marked eosinophilia and high levels of thymus and activation‐regulated chemokine and interleukin‐5 in the serum. These results indicated a novel autoantigen on the nondesmosomal keratinocyte cell surfaces and the pathogenesis of bullous spongiotic change with inflammation in HP. What's already known about this topic? Herpetiform pemphigus (HP) is a rare variant of pemphigus characterized clinically by pruritic annular erythemas with vesicles resembling dermatitis herpetiformis and histopathologically by eosinophilic spongiosis without apparent acantholysis.The targets of IgG autoantibodies in patients with HP are usually desmoglein 1 and 3, which are both components of desmosomes. What does this study add? This study reports the unique case of a patient with HP with IgG autoantibodies reactive to nondesmosomal sites of keratinocytes and characteristic transmission electron microscopic findings of various‐sized vacuoles in keratinocytes, while desmosomal adhesion remained.Regarding pathogenesis, we speculate that the ballooning vacuoles might result in the bullous spongiotic changes without acantholysis seen in this patient.This study also focuses on the relationships between blood eosinophil counts, serum thymus and activation‐regulated chemokine levels and HP disease activity. Linked Comment: Yuan and Pan. Br J Dermatol 2019; 180:22. [ABSTRACT FROM AUTHOR]

Background: Vibrio parahaemolyticus causes acute gastroenteritis and inflammations in humans. A variety of pathogenic bacteria can stimulate mitogen-activated protein kinases (MAPKs) in host cells. Phosphorylation of MAPKs leads to production of interleukin (IL)- 8 and subsequently causes inflammations. Thus, MAPK cascades were strong candidates for the main signaling pathway of V. parahaemolyticus-induced acute inflammation.Methods: To determine whether the signaling pathway on V. parahaemolyticus infection induces inflammation, we analyzed the secretion level of IL-8 and phosphorylation of MAPKs by use of intestinal epithelial Caco-2 cells.Results: V. parahaemolyticus infection of Caco-2 cells activated extracellular signal-regulated kinase (ERK) 1/2 and p38 MAPK signal pathways, leading to IL-8 secretion, whereas MAPK inhibitors, UO126 or SB203580, suppressed IL-8 secretion. A strain carrying a deletion of VP1680, a type three secretion system 1 (T3SS1) effector protein, failed to activate phosphorylation of ERK1/2 and p38 MAPK and secretion of IL-8. ERK1/2 pathway inhibitor, UO126, failed IL-8 promoter activity, whereas p38 MAPK inhibitor, SB203580, decreased the stabilization of IL-8 messenger RNA following V. parahaemolyticus infection.Conclusions: We showed that V. parahaemolyticus infection of Caco-2 cells results in the secretion of IL-8, and that VP1680 plays a pivotal role in manipulating host cell signaling and is responsible for triggering IL-8 secretion. [ABSTRACT FROM AUTHOR]

Neoplastic B cells from two patients with hyperleucocytic hairy cell leukaemia (HCL) and 19 patients with chronic lymphocytic leukaemia of B cell Type (B-CLL) were investigated to examine the mitogenic responses to the F(ab')2 fraction of anti-human immunoglobulins (anti-Igs) and Staphylococcus aureus Cowan I (STA). Neoplastic cells from both HCL patients lacked surface Tac antigen. Mononuclear cells from the two HCL patients strongly responded to both anti-Igs and STA as measured by 3H-thymidine incorporation in vitro. Although the mononuclear cells from two patients with B-CLL showed high response to STA. cells from none of the patients with B-CLL responded to anti-Igs. Mononuclear cells as well as T-cell-depleted fractions from the two HCL patients showed a strong proliferative response by anti γ chain antibody (anti-γ) and the mononuclear cells from one of the patients were also induced to proliferate by anti-δ, whereas those from normal subjects responded only to a high concentration of anti-μ. Based on the difference in reactivity to anti-Ig, it is suggested that the HCL cells in this study originate from a subset equivalent to 'memory' B cells, whereas the B-CLL cells originate from a subset equivalent to 'virgin' B cells. [ABSTRACT FROM AUTHOR]

Anti-p80-coilin antibody produces a unique pattern of immunofluorescence staining called nuclear dots characterized by the presence of up to six discrete nuclear bodies in interphase cell nuclei. The distribution of this antibody and its clinical relevance have not been established. We studied the prevalence of anti-p80-coilin antibody in the sera from 810 patients with collagen diseases and various skin diseases. Five sera showed the nuclear dot pattern by indirect immunofluorescence on an HEp-2 cell substrate, and reacted by immunoblotting with 80-kDa protein in a nuclear extract from HeLa cells. Pour of these sera were from patients with localized scleroderma, and the other was from a patient with primary Raynaud's phenomenon. The patients with localized scleroderma who were positive for anti-p80-coilin antibody had all been classified as having linear scleroderma. They had only one or two lesions, and were negative for antihistone and anti-single-stranded DNA antibodies. Our data indicate that anti-p80-coilin antibody is uncommon in skin diseases; however, this antibody is present in patients with a milder form of linear scleroderma, although the incidence of positivity may not he high. [ABSTRACT FROM AUTHOR]

Sera from patients with localized scleroderma frequently produce cytoplasmic staining by indirect immunofluorescence, although the antigen remains to be determined. We studied the prevalence, antigen specificity and associated clinical characteristics of anti-cytoplasmic antibodies in localized scleroderma. Serum samples from 60 patients with localized scleroderma were examined by indirect Immunofluorescence analysis and immunoblotting. By immunofluorescence analysis on HEp-2 cell substrate, seven of 60 (12%) patients were shown to be positive for anti-cytoplasmic antibodies. Among these, six patients with generalized morphea had anti-mitochondrial antibodies as shown by immunoblotting: they showed reactivity with the E2 component of pyruvate dehydrogenase complex (PDC), with protein X, and with the E2 component of α-oxo-glutarate dehydrogenase complex, while two of them showed reactivity with PDC-E1α. One of these patients who was positive for anti-PDC-E1α antibody showed laboratory abnormalities, suggesting the presence of primary biliary cirrhosis. The age of disease onset was significantly higher in these six patients than in those without anti-mitochondrial antibodies. Furthermore, five of them were classified into generalized morphea with multiple plaque lesions but without linear lesions (multiple plaque type). These observations suggest that major antigens for anti-cytoplasmic antibodies in patients with localized scleroderma are mitochondrial enzymes, 2-oxo-acid dehydrogenase complexes. Patients with anti-mitochondrial antibodies may comprise a unique subset of localized scleroderma designated multiple plaque type of generalized morphea of older onset. [ABSTRACT FROM AUTHOR]

Peripheral blood T cells from 40 patients with idiopathic thrombocytopenic purpura (ITP) were analysed for the presence of surface la antigens using monoclonal antibodies by indirect immunofluorescence. The percentage of la-positive (Ia &plus;) T cells was significantly increased in patients with ITP (6.8±2.9%. P<0.005) as compared with normal controls (2.3 ± 0.9%), There was an inverse correlation between the percentages of Ia+ T cells and platelet counts (r = 0.58, P<0.005)and a positive correlation between the percentage of these cells and platelet-associated IgG (PAIgG) values (r = 0.55, P<0.01), The percentage of la+ T cells was found to decrease within two weeks during therapy with high dose γ - globulin or corticosteroid. We have previously reported the presence of T cells bearing both helper/inducer (H/I) and suppressor/cytotoxic (S/C) phenotypes (double labelled cells. DI.C) in patients with ITP and an inverse correlation between the percentages of DLC and their platelet counts. In the present study, we showed that a major part of Ia+ T cells had both H/I and S/C phenotypes. We also examined the correlation between Ia+ T cells and autologous mixed lyniphocyle reaction (AMLR). A defective AMLR was demonstrated in patients with ITP. Furthermore, an inverse correlation was found between the percentages of la+ T cells and the proliferative responses to AMLR (r= --0.49, P< 0.01). These results suggest that increased circulating Ia+ T cells play a role in the abnormalities of the immunoregulatory system of ITP. especially in the regulation of autoantibody production. [ABSTRACT FROM AUTHOR]

T cell subsets of peripheral lymphocytes were studied using monoclonal antibodies (OKT3. OKT4, OKT8) and immunoglobulin (IgG, IgM, IgA) synthesis in vitro by peripheral mononuclear cells stimulated with pokeweed mitogen was studied in adult patients with idiopathic thrombocytopenic purpura before and after high-dose intra-venous intact gamma(γ-)globulin therapy, at a daily dose of 0.4g/kg body weight for 5 consecutive days. A transient increase in platelet count which reached a peak on the 1st to 2nd day after the end of the therapy was observed in four of five patients. Immunoglobulin synthesis in vitro was suppressed remarkably following therapy in all cases: the mean reduction of IgG, IgM and IgA was 78, 66 and 48% respectively. Titres of various autoantibodies, TGHA, MCHA, ANF and anti-DNA antibody, also decreased following therapy. In correspondence to this, phenotypic analysis in T cell subsets showed a decrease of OKT4+ : OKT8+ ratio following therapy, without a change in the proportion of OKT3+ cells. These data indicate that the intravenous γ-globulin preparations suppressed synthesis of antibodies non-specificially and caused a relative increase of OKT8+ suppressor T cells. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Episodic angioedema associated with eosinophilia.