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M M Black - One of the best experts on this subject based on the ideXlab platform.

  • current management of Pemphigoid Gestationis
    2015
    Co-Authors: Clarisse Garcia Mendoza, M M Black, Dedee F Murrell
    Abstract:

    Pemphigoid Gestationis is a rare autoimmune blistering disease of pregnancy involving autoantibodies targeting collagen XVII in the basement membrane zone of the skin. Patients usually present with pruritic urticarial papules and annular plaques eventually developing vesicles and tense bullae ranging from a few days to 4 weeks. The most common site for the lesions is the periumbilical area. Diagnosis is made by a high clinical suspicion on presentation and confirmed by histology and direct immunofluorescence. If required, indirect immunofluorescence, enzyme-linked immunosorbent assay, and immunoblotting may be done. Current management includes topical and systemic steroids, anti-inflammatory antibiotics, and immunosuppressives.

  • Pemphigoid Gestationis current insights into pathogenesis and treatment
    European Journal of Obstetrics & Gynecology and Reproductive Biology, 2009
    Co-Authors: Kristina Semkova, M M Black
    Abstract:

    Normal pregnancy is characterized by a natural homeostasis between the mother and the fetus with the development of a tolerance for genetically and immunologically different tissues engrafted in the maternal organism. Upset of the fine mechanisms of the balance of this homeostasis leads to the development of different diseases. Pemphigoid Gestationis is a self-limiting, autoimmune subepidermal bullous dermatosis of pregnancy that results from the recognition of placental proteins as foreign and the subsequent production of anti-placental antibodies that cross-react with the same proteins in skin. The main antigen of PG was found to be collagen XVII, present in both skin and placenta, that is exposed to the maternal immune system through an abnormal expression of MHC class II molecules in the placenta. The genetic predisposition determined by a specific HLA genotype combined with the aberrant presentation of collagen XVII triggers an inflammatory response resulting in the typical clinical phenotype. Immunofluorescence shows a linear deposition of C3 with or without concomitant IgG deposition, along the basement membrane zone (BMZ). The disease usually resolves within weeks to months after delivery and tends to recur with subsequent pregnancies. Treatment is challenging in that the disease is extremely rare to allow for controlled studies and most of the treatment options are based on case reports and clinical experience. Oral corticosteroids are the therapeutic mainstay both in pregnancy and postpartum, but several other modalities may be tried in recalcitrant disease. Further research is needed to clarify the exact pathogenic cascade and the interaction of its different components. The elucidation of the target antigens, the targeting antibodies and the mechanism of action of the inflammatory infiltrate may help for the development of new focused therapeutic agents. This review presents an overview of the current understanding of Pemphigoid Gestationis and the latest scientific and clinical data in relation to the pathogenesis and treatment modalities.

  • Pemphigoid Gestationis early onset and blister formation are associated with adverse pregnancy outcomes
    British Journal of Dermatology, 2009
    Co-Authors: Chingchi Chi, M M Black, S H Wang, R Charlesholmes, C Ambrosrudolph, J Powell, R Jenkins, F Wojnarowska
    Abstract:

    Summary Background  It is unclear whether clinical features of Pemphigoid Gestationis (PG), such as timing of onset and severity, may affect pregnancy outcomes or whether the adverse outcomes in pregnancies complicated by PG are related to or worsened by systemic corticosteroid treatment. Objectives  To evaluate the associations of adverse pregnancy outcomes with clinical features, autoantibody titre of PG, and systemic corticosteroid treatment. Methods  We conducted a retrospective cohort study recruiting 61 pregnancies complicated by PG from the St John’s Institute of Dermatology database which enrolled cases from dermatologists across the U.K., and two tertiary hospitals in the U.K. and Taiwan. Outcome measures included gestational age at delivery, preterm birth, birthweight, low birthweight (LBW, i.e. birthweight < 2500 g), small-for-gestational-age (i.e. birthweight below the 10th percentile for gestational age), fetal loss, congenital malformation, and mode of delivery. Results  After controlling for maternal age and comorbidity, decreased gestational age at delivery was significantly associated with presence of blisters (P = 0·017) and disease onset in the second trimester (P = 0·001). Reduced birthweight was significantly associated with disease onset in the first and second trimesters (P = 0·030 and 0·018, respectively) as was also LBW [adjusted odds ratio (95% confidence interval) 13·71 (1·22–154·59) and 10·76 (1·05–110·65), respectively]. No significant associations of adverse pregnancy outcomes with autoantibody titre or systemic corticosteroid treatment were found. Conclusions  Onset of PG in the first or second trimester and presence of blisters may lead to adverse pregnancy outcomes including decreased gestational age at delivery, preterm birth, and LBW children. Such pregnancies should be considered high risk and appropriate obstetric care should be provided. Systemic corticosteroid treatment, in contrast, does not substantially affect pregnancy outcomes, and its use for PG in pregnant women is justified.

  • usefulness of bp180 nc16a enzyme linked immunosorbent assay in the serodiagnosis of Pemphigoid Gestationis and in differentiating between Pemphigoid Gestationis and pruritic urticarial papules and plaques of pregnancy
    Archives of Dermatology, 2005
    Co-Authors: Ann Marie Powell, Balbir S. Bhogal, Takeji Nishikawa, Y Sakumaoyama, Noritaka Oyama, Sandra Albert, Fumio Kaneko, M M Black
    Abstract:

    Background: Pemphigoid Gestationis (PG) is a rare pregnancy-associated subepidermal immunobullous disease that targets hemidesmosomal proteins, particularly BP180. Clinically, PG can resemble the eruption known as polymorphic urticarial papules and plaques of pregnancy (PUPPP), and accurate differentiation between these 2 pruritic pregnancy dermatoses has important implications for fetal and maternal prognoses. Results of epitope mapping studies show that IgG autoantibodies in up to 90% of PG serum samples target the well-defined membrane-proximal NC16a domain of BP180. Objective: To examine the usefulness of a commercially available NC16a domain enzyme-linked immunosorbent assay in the serodiagnosis of PG and in the differentiation of PG from PUPPP. Participants: A total of 412 women consisting of pretreatment patients with PG (n=82), patients with PUPPP (n=164), and age- and sex-matched controls (n=166). Methods: All serum samples were assayed in duplicate. Receiver operating characteristic analyses were performed to determine a cutoff value for the diagnosis of PG and for differentiation from PUPPP and controls. Results: A cutoff value of 10 enzyme-linked immunosorbent assay units was associated with specificity and sensitivity of 96%. Conclusions: The NC16a enzyme-linked immunosorbent assay is highly sensitive and highly specific in differentiating PG from PUPPP, and it is potentially a valuable tool in the serodiagnosis of PG. Arch Dermatol. 2005;141:705-710

  • clinical features and management of 87 patients with Pemphigoid Gestationis
    Clinical and Experimental Dermatology, 1999
    Co-Authors: R E Jenkins, S Hern, M M Black
    Abstract:

    Pemphigoid Gestationis is a rare vesiculo-bullous disorder of pregnancy. In this review we summarize the clinical data on 142 pregnancies in 87 patients complicated by Pemphigoid Gestationis. Our aim is to provide a comprehensive clinical overview of this disease.

Detlef Zillikens - One of the best experts on this subject based on the ideXlab platform.

  • Pemphigoid Gestationis toward a better understanding of the etiopathogenesis
    Clinics in Dermatology, 2016
    Co-Authors: Christian D Sadik, Ana Luiza Lima, Detlef Zillikens
    Abstract:

    Pemphigoid Gestationis (PG) is the only autoimmune disease exclusively emerging in pregnancy. It belongs to the Pemphigoid group of disorders, a class of autoimmune blistering skin diseases featuring an immune response against different hemidesmosomal proteins. PG is caused by a break of immunotolerance against the hemidesmosomal protein BP180. Several lines of evidence suggest that this break of immunotolerance is linked to specific maternal major histocompatibility complex (MHC) class II gene variants and aberrant expression of MHC class II molecules in the placenta. The close time association of the emergence of PG with pregnancy and the obviously very short period required from the initial break of immunotolerance to the onset of skin inflammation set PG into a unique position among autoimmune diseases in view of the fact that, for other autoimmune diseases, the time and site of the break of immunotolerance are usually vastly elusive and the period of silent disease can only be speculated on. In this review we highlight the features of PG and summarize current knowledge about its pathogenesis. We believe that this disease offers the best opportunity to elucidate comprehensively all phases of the pathogenesis of an autoantibody-driven disease.

  • Josep E. Herrero-Gonzlez1,2, Olaf Brauns3, Ralf Egner3,
    2015
    Co-Authors: Marcel F Jonkman, Detlef Zillikens, Cassian Sitaru
    Abstract:

    Immunoadsorption against two distinct epitopes on human type XVII collagen abolishes dermal-epidermal separation induced in vitro by autoantibodies from Pemphigoid Gestationis patient

  • glucocorticosteroid resistant Pemphigoid Gestationis successful treatment with adjuvant immunoadsorption
    Journal of Dermatology, 2012
    Co-Authors: Lilia Westermann, Detlef Zillikens, Rainer Hugel, Markus Meier, Michael Weichenthal, Regine Glaser, Enno Schmidt
    Abstract:

    A 40-year old prima para presented with multiple urticaria-like plaques and severe pruritus 2 weeks prior to giving birth by cesarean section. Three days after birth, the disease flared up and tense blisters appeared on hands, lower arms and feet. Based on the clinical presentation, direct immunofluorescence microscopy, complement binding test and detection of high levels of circulating anti-BP180 antibodies, the diagnosis of Pemphigoid Gestationis was established. Despite treatment with class IV topical corticosteroid and prednisolone p.o. up to 60 mg/day, both skin lesions and severe pruritus progressed accompanied by increasing anti-BP180 antibody serum levels. In order to continue breast feeding, the prednisolone dose could not be further increased and 10 immunoadsorptions over 4 weeks were performed. During this period, skin lesions cleared rapidly, pruritus subsided and BP180-specific serum autoantibodies decreased by 99.5% allowing the reduction of prednisolone to 7.5 mg/day. We conclude that immunoadsorption is an effective and safe adjuvant therapeutic option for severe Pemphigoid Gestationis.

  • immunoadsorption against two distinct epitopes on human type xvii collagen abolishes dermal epidermal separation induced in vitro by autoantibodies from Pemphigoid Gestationis patients
    European Journal of Immunology, 2006
    Co-Authors: Detlef Zillikens, J M Mascaro, Josep E Herrerogonzalez, Olaf Brauns, Ralf Egner, Wolfgang Ronspeck, Marcel F Jonkman, Cassian Sitaru
    Abstract:

    Pemphigoid Gestationis (PG) is a subepidermal autoimmune blistering disease characterized by self-reactive T and B cells specific for the transmembrane hemidesmosomal protein type XVII collagen/BP180. Major T and B cell epitopes are located within the immunodominant 16(th) non-collagenous domain A (NC16A) of type XVII collagen. The aim of the present study was to map the pathogenically relevant epitopes targeted by blister-inducing patients'autoantibodies. For this purpose, we used an in vitro model of autoantibody-induced leukocyte-dependent dermal-epidermal separation. Pre-adsorption against a recombinant form of the NC16A region abolished the blister-inducing potential of autoantibodies from all PG patients. Using overlapping synthetic peptides, we demonstrated that PG autoantibodies bind to two defined epitopes within the NC16A region (aa 500-514 and aa 511-523). Importantly, pre-adsorption using an affinity matrix containing these epitopes completely abolished dermal-epidermal separation induced by PG autoantibodies. This study identifies the epitopes relevant for blister induction in PG and should facilitate the development of an antigen-specific immunoadsorption therapy for this disease.

  • t cell receptor gene usage of bp180 specific t lymphocytes from patients with bullous Pemphigoid and Pemphigoid Gestationis
    Clinical Immunology, 2004
    Co-Authors: Mary K Hackerfoegen, Detlef Zillikens, George J Giudice, Mongshang Lin
    Abstract:

    BP180 is the autoantigen of different immunobullous diseases, including bullous Pemphigoid (BP) and Pemphigoid Gestationis (PG). Previously, we demonstrated that the NC16A domain of this autoantigen harbors key epitopes of autoantibodies and T cells, indicating that it plays an essential role in the pathogenesis of diseases. Moreover, NC16A-specific T cell clones derived from these patients were shown to express a CD4+ memory T cell phenotype and secrete cytokines that may promote autoantibody production. In this study, we further characterize the properties of these T cells by analyzing their epitope specificity and T cell receptor (TCR) gene usage. We discovered that 83% of T cell clones obtained from BP patients preferentially express TCRBV13, while clones derived from a PG patient express the TCRBV3 gene. However, no preferential TCRBJ gene usage was identified. In conclusion, our results provide an advanced understanding of the characteristics of autoimmune T cells in immunobullous diseases.

Simon Francis Thomsen - One of the best experts on this subject based on the ideXlab platform.

Cassian Sitaru - One of the best experts on this subject based on the ideXlab platform.

  • Pemphigoid Gestationis with igg autoantibodies to both the 120 kda lad 1 and the bp180 nc16a domain
    European Journal of Dermatology, 2015
    Co-Authors: Naoko Takayama, Cassian Sitaru, Takashi Hashimoto, Sonoko Nakazono, Jiro Kumagai, Roxana Chiorean, Norito Ishii, Takeshi Namiki
    Abstract:

    Pemphigoid Gestationis (PG) patients usually show IgG autoantibodies to the NC16a domain of BP180 but autoantibodies to the 120 kDa LAD-1 are detected in 20% of PG patients [1]. We describe a PG case, which showed IgG autoantibodies to the 120 kDa LAD-1 in addition to the BP180 NC16a domain, and discuss a putative role of 120 kDa LAD-1 in the pathogenesis of PG.A 35-year-old Japanese female, who was primigravida, first developed pruritic erythema multiforme-like lesions on her trunk and extremities [...]

  • Josep E. Herrero-Gonzlez1,2, Olaf Brauns3, Ralf Egner3,
    2015
    Co-Authors: Marcel F Jonkman, Detlef Zillikens, Cassian Sitaru
    Abstract:

    Immunoadsorption against two distinct epitopes on human type XVII collagen abolishes dermal-epidermal separation induced in vitro by autoantibodies from Pemphigoid Gestationis patient

  • immunoadsorption against two distinct epitopes on human type xvii collagen abolishes dermal epidermal separation induced in vitro by autoantibodies from Pemphigoid Gestationis patients
    European Journal of Immunology, 2006
    Co-Authors: Detlef Zillikens, J M Mascaro, Josep E Herrerogonzalez, Olaf Brauns, Ralf Egner, Wolfgang Ronspeck, Marcel F Jonkman, Cassian Sitaru
    Abstract:

    Pemphigoid Gestationis (PG) is a subepidermal autoimmune blistering disease characterized by self-reactive T and B cells specific for the transmembrane hemidesmosomal protein type XVII collagen/BP180. Major T and B cell epitopes are located within the immunodominant 16(th) non-collagenous domain A (NC16A) of type XVII collagen. The aim of the present study was to map the pathogenically relevant epitopes targeted by blister-inducing patients'autoantibodies. For this purpose, we used an in vitro model of autoantibody-induced leukocyte-dependent dermal-epidermal separation. Pre-adsorption against a recombinant form of the NC16A region abolished the blister-inducing potential of autoantibodies from all PG patients. Using overlapping synthetic peptides, we demonstrated that PG autoantibodies bind to two defined epitopes within the NC16A region (aa 500-514 and aa 511-523). Importantly, pre-adsorption using an affinity matrix containing these epitopes completely abolished dermal-epidermal separation induced by PG autoantibodies. This study identifies the epitopes relevant for blister induction in PG and should facilitate the development of an antigen-specific immunoadsorption therapy for this disease.

  • immunoblotting and enzyme linked immunosorbent assay for the diagnosis of Pemphigoid Gestationis
    Obstetrics & Gynecology, 2004
    Co-Authors: Cassian Sitaru, F Wojnarowska, Jenny Powell, Gerald Messer, Evabettina Brocker, Detlef Zillikens
    Abstract:

    OBJECTIVES To investigate the sensitivity of immunoblotting and enzyme-linked immunosorbent assay (ELISA) to detect autoantibodies to bullous Pemphigoid antigen 180 in patients with Pemphigoid Gestationis and to correlate autoantibody serum levels with disease activity. METHODS In serum samples obtained from 44 pregnant patients before initiation of therapy and from the same number of healthy blood donors, the autoantibody reactivity was assayed by immunofluorescence microscopy on human skin sections as well as Western blot analysis and 2 different ELISAs by using recombinant forms of the immunodominant domain of BP180. In addition, ELISA reactivity with this autoantigen was assayed in 6 patients during the course of the disease, and its correlation with the clinical disease activity was estimated by applying the Spearman rank correlation test. RESULTS By indirect immunofluorescence microscopy, complement-fixing autoantibodies to the dermal-epidermal junction were found in 93% of patients' sera. By immunoblotting and ELISA, autoantibodies to bullous Pemphigoid antigen 180 were detected in 93% and 86.3% of Pemphigoid Gestationis patients, respectively, but in none of the healthy controls. Serum levels of autoantibodies as detected by ELISA paralleled the patients' disease activity. CONCLUSIONS Our study shows that immunoblotting and ELISA are sensitive tools for the detection of autoantibodies to bullous Pemphigoid antigen 180 in patients with Pemphigoid Gestationis. In addition, the ELISA is useful to monitor autoantibody serum levels. LEVEL OF EVIDENCE II-2

Christine Savervall - One of the best experts on this subject based on the ideXlab platform.