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1.
Br J Dermatol ; 185(3): 595-604, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33792909

RESUMO

BACKGROUND: Pemphigus is a severe bullous autoimmune skin disease. Pemphigus foliaceus (PF) is characterized by antidesmoglein (Dsg) 1 IgG causing epidermal blistering; mucosal pemphigus vulgaris (mPV) by anti-Dsg3 IgG inducing erosions in the mucosa; and mucocutaneous pemphigus vulgaris (PV) by affecting both, with autoantibodies targeting Dsg1 and Dsg3. OBJECTIVES: To characterize the Ca2+ flux pathway and delineate its importance in pemphigus pathogenesis and clinical phenotypes caused by different antibody profiles. METHODS: Immunoprecipitation, Ca2+ flux analysis, Western blotting, immunofluorescence staining, dissociation assays and a human skin ex vivo model were used. RESULTS: PV IgG and PF IgG, but neither Dsg3-specific monoclonal antibody (AK23) nor mPV IgG, caused Ca2+ influx in primary human keratinocytes. Phosphatidylinositol 4-kinase α interacts with Dsg1 but not with Dsg3. Its downstream target - phospholipase-C-γ1 (PLC) - was activated by PV IgG and PF IgG but not AK23 or mPV IgG. PLC releases inositol 1,4,5-trisphosphate (IP3) causing IP3 receptor (IP3R) activation and Ca2+ flux from the endoplasmic reticulum into the cytosol, which stimulates Ca2+ release-activated channels (CRAC)-mediated Ca2+ influx. Inhibitors against PLC, IP3R and CRAC effectively blocked PV IgG and PF IgG-induced Ca2+ influx; ameliorated alterations of Dsg1 and Dsg3 localization, and reorganization of keratin and actin filaments; and inhibited loss of cell adhesion in vitro. Finally, inhibiting PLC or IP3R was protective against PV IgG-induced blister formation and redistribution of Dsg1 and Dsg3 in human skin ex vivo. CONCLUSIONS: Ca2+ -mediated signalling is important for epidermal blistering and dependent on the autoantibody profile, which indicates different roles for signalling complexes organized by Dsg1 and Dsg3. Interfering with PLC and Ca2+ signalling may be a promising approach to treat epidermal manifestations of pemphigus.


Assuntos
Pênfigo , Autoanticorpos , Vesícula , Desmogleína 1 , Desmogleína 3 , Epiderme , Humanos , Imunoglobulina G
3.
Hautarzt ; 70(4): 236-242, 2019 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-30874841

RESUMO

BACKGROUND: Bullous pemphigoid, the most common autoimmune blistering disease of the skin in adults, is caused by autoantibodies against hemidesmosomal adhesion proteins (BP180/type XVII collagen and BP230), leading into subepidermal blistering. Therefore patients, mostly older than 70 years, show tight bullae and erosions of the skin and rarely at mucous membranes. PROBLEM: Usually the disease shows a chronically relapsing course. Thus there is a need for long-term topical corticosteroids and if necessary systemic immunosuppressives. Still there is no curative treatment available. In the context of a long-term treatment, drug-specific side effects and also a patient's comorbidities have to be taken into account. CONCLUSION: The choice of treatment should be based on disease activity and the extent of the muco-cutaneous manifestations. Dependent on this, high-potent topical class IV corticosteroids are used because of fewer side effects compared to systemic steroids. In case of an intense disease extent or in refractory courses treatment with systemic corticosteroids is usually combined with potentially corticosteroid-sparing immunomodulants such as dapsone or doxycycline or adjuvant immunosuppressives such as azathioprine, mycophenoles or methotrexate. Medium- to long-term an attendant immunosuppressant should be applied to reduce the use of corticosteroids. The CD20-antibody rituximab and high-dose intravenous immunoglobulins are also supplemental off-label options in refractory cases.


Assuntos
Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Penfigoide Bolhoso/diagnóstico , Penfigoide Bolhoso/imunologia , Dermatopatias Vesiculobolhosas/diagnóstico , Dermatopatias Vesiculobolhosas/imunologia , Pele/imunologia , Adulto , Autoanticorpos/imunologia , Autoantígenos , Doenças Autoimunes/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Penfigoide Bolhoso/tratamento farmacológico , Pele/patologia , Dermatopatias Vesiculobolhosas/tratamento farmacológico
4.
J Eur Acad Dermatol Venereol ; 33(4): 735-741, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29972879

RESUMO

BACKGROUND: Anti-laminin-γ1 (lam-γ1) pemphigoid, a recently described immunobullous disorder sharing immune serological features of bullous pemphigoid and epidermolysis bullosa acquisita (EBA), is characterized by the detection of serum IgG autoantibodies against the lam-γ1 chain, a 200 kDa heterotrimeric component of the dermal-epidermal junction (DEJ). OBJECTIVE: The aim of the study was to develop an easy-to-perform and reliable assay for the serological detection of anti-lam-γ1 IgG autoantibodies. The clinical appearance alone is not sufficient to establish diagnosis of anti-lam-γ1 pemphigoid and rather requires immune serological evidence of (i) IgG reactivity against the dermal portion of salt-split human skin; (ii) exclusion of IgG against other components of the DEJ; and (iii) IgG reactivity with a 200 kDa protein of dermal extracts by immunoblot analysis (IB). METHODS: The sera of 55 patients with anti-lam-γ1 pemphigoid were tested by IB with two recombinant heterotrimers, laminin 111 (lam-111) and laminin 421 (lam-421), as well as with a recombinant lam-γ1 chain monomer. Additionally, a total of 41 control sera from patients with EBA (n = 15), psoriasis vulgaris (PV; n = 14), and healthy controls (HC; n = 12) were tested. RESULTS: Immunoblot analysis revealed a positive reactivity with lam-111 and/or lam-421 in 46/55 (84%) of anti-lam-γ1 pemphigoid sera. Moreover, 8/9 of the initially non-reactive sera were positive with the lam-γ1 monomer, leading to an overall sensitivity of 98.2%. Analyses of 41 control sera with the three lam-γ1 recombinants led to a specificity of 88%. Specifically, 3/15 EBA sera, 1/14 PV serum and 1/12 HC serum reacted with the lam-γ1 monomer while only the 3 EBA sera reacted with lam-421. CONCLUSIONS: Here we show a novel two-step IB assay using the two recombinant laminin trimers and lam-γ1 chain monomer for the detection of anti-lam-γ1 serum IgG with high sensitivity and specificity. This assay will facilitate the diagnosis and further characterization of this disease.


Assuntos
Autoanticorpos/sangue , Imunoglobulina G/sangue , Laminina/imunologia , Penfigoide Bolhoso/diagnóstico , Penfigoide Bolhoso/imunologia , Dermatite de Contato , Feminino , Humanos , Immunoblotting/métodos , Masculino , Pessoa de Meia-Idade , Penfigoide Bolhoso/sangue , Proteínas Recombinantes , Testes Sorológicos
5.
Br J Dermatol ; 177(6): 1683-1692, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28703393

RESUMO

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a rare, potentially devastating autoimmune disease of the skin. IgG autoantibodies directed against type VII collagen (Col7), the major component of anchoring fibrils, induce skin fragility leading to cutaneous and mucocutaneous blister formation, which is mostly of a scarring phenotype. Thus, powerful and reproducible diagnostic assays are critical to establish the diagnosis of EBA early to avoid irreversible sequelae. OBJECTIVES: The present international, retrospective multicentre study included a large cohort of patients with EBA and evaluated the diagnostic power of four different diagnostic assays for the detection of anti-Col7 IgG autoantibodies. METHODS: Overall, 95 EBA sera and 200 control sera consisting of 100 bullous pemphigoid sera, 50 pemphigus vulgaris sera and 50 sera of healthy controls were tested for anti-Col7 IgG autoantibodies using indirect immunofluorescence (IIF), two commercial enzyme-linked immunosorbent assay (ELISA) systems and Western blot (WB) analysis. EBA sera were taken from patients with positive direct immunofluorescence and IgG reactivity in at least one of the immunoserological assays (IIF, ELISA, WB). RESULTS: A Col7-NC1/NC2 ELISA (MBL, Nagoya, Japan) showed the highest sensitivity (97·9%), followed by a Col7-NC1 ELISA (Euroimmun, Lübeck, Germany) (89·5%), WB with Col7-NC1 (85·3%), and IIF on saline-split human skin (74·7%). The specificities of both ELISA systems were comparable (NC1 98·7%, NC1/NC2 99·3%). Furthermore, WB was more sensitive than IIF, which was more specific. CONCLUSIONS: The two commercially available ELISA systems allow for a highly sensitive and specific diagnosis of EBA. The sensitivity of the Col7-NC1/NC2 ELISA is significantly higher compared with the ELISA based on the Col7-NC1 domain only.


Assuntos
Autoanticorpos/metabolismo , Colágeno Tipo VII/imunologia , Epidermólise Bolhosa Adquirida/diagnóstico , Imunoglobulina G/metabolismo , Vesícula/imunologia , Western Blotting , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina G/imunologia , Microscopia de Fluorescência , Estudos Retrospectivos
7.
J Eur Acad Dermatol Venereol ; 30(10): 1657-1669, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27406069

RESUMO

BACKGROUND: The treatment of severe dermatological autoimmune diseases and toxic epidermal necrolysis (TEN) with high-dose intravenous immunoglobulin (IVIg) is a well-established procedure in dermatology. As treatment with IVIg is usually considered for rare clinical entities or severe clinical cases, the use of immunoglobulin is not generally based on data from randomized controlled trials that are usually required for the practice of evidence-based medicine. Owing to the rarity of the indications for the use of IVIg, it is also unlikely that such studies will be available in the foreseeable future. Because the high costs of IVIg treatment also limit its first-line use, the first clinical guidelines on its use in dermatological conditions were established in 2008 and renewed in 2011. MATERIALS AND METHODS: The European guidelines presented here were prepared by a panel of experts nominated by the EDF and the EADV. The guidelines were developed to update the indications for treatment currently considered as effective and to summarize the evidence base for the use of IVIg in dermatological autoimmune diseases and TEN. RESULTS AND CONCLUSION: The current guidelines represent consensual expert opinions and definitions on the use of IVIg reflecting current published evidence and are intended to serve as a decision-making tool for the use of IVIg in dermatological diseases.


Assuntos
Doenças Autoimunes/terapia , Imunoglobulinas Intravenosas/administração & dosagem , Dermatopatias/terapia , Europa (Continente) , Humanos , Imunoglobulinas Intravenosas/uso terapêutico
8.
Hautarzt ; 66(8): 574-82, 2015 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-26231572

RESUMO

BACKGROUND: Pemphigus is a severe bullous autoimmune dermatosis that represents a clinical challenge despite high-dose immunosuppressive therapy due to the therapy-related comorbidities and the lack of long-term control of disease activity. OBJECTIVES: Which targeted therapies are currently used in pemphigus and which innovative therapeutic strategies are in clinical development? MATERIALS AND METHODS: A review of the literature in PubMed was performed under consideration of the current guideline for the treatment of pemphigus as well as of our own results. Discussion of basic findings and results of targeted therapies in autoantibody-mediated autoimmune disorders were taken into account. RESULTS: Immunapheresis and high-dose intravenous immunoglobulins with the aim of reducing circulating autoantibodies have been successfully used in the treatment of pemphigus. Depletion of autoreactive B-lymphocytes provides the rationale for the use of the monoclonal anti-CD20 antibody rituximab which demonstrated long-term clinical remission of pemphigus in clinical trials. Current developments include the investigation of humanised B-cell depleting antibodies in other B-cell driven autoimmune disorders as well as the identification of new cellular and molecular target structures that are essential in the humoral autoimmune cascade and exert important immune regulatory functions, respectively. CONCLUSIONS: The well-characterised basic pathogenesis of pemphigus results in targeted therapies. Currently, therapies aiming at rapid reduction of circulating autoantibodies and the depletion of autoreactive B-cells are in clinical use. More cellular and molecular target structures are being investigated in other autoantibody-driven autoimmune disorders and they provide promising candidates for innovative pathogenesis-related therapeutic strategies in pemphigus in the future.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Linfócitos B/imunologia , Fatores Imunológicos/uso terapêutico , Terapia de Alvo Molecular/métodos , Pênfigo/imunologia , Pênfigo/terapia , Humanos , Pênfigo/diagnóstico
10.
Br J Dermatol ; 171(3): 650-6, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24601812

RESUMO

IgA pemphigus (IGAP) is a rare, distinct variant of pemphigus, currently classified, depending upon the histological features, immunofluorescence staining pattern and autoantibody profile, into two types: subcorneal pustular dermatosis (SPD) and intraepidermal neutrophilic IgA dermatosis. In a patient with a widespread blistering disease of the skin resembling SPD-type IGAP, we demonstrate the coexistence of IgA reactivity to both epidermal (desmocollins 2 and 3) and basement membrane-associated (BP180) proteins, suggesting the coexistence of atypical IGAP and linear IgA bullous dermatosis, respectively. This case, together with 20 previous reports of atypical IGAP, underscores the limitations of current classification schemes. Therefore, we suggest reclassifying these cases under the general term 'IGAP spectrum'.


Assuntos
Imunoglobulina A/imunologia , Pênfigo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoantígenos/imunologia , Criança , Desmocolinas/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Colágenos não Fibrilares/imunologia , Pênfigo/imunologia , Colágeno Tipo XVII
11.
Unfallchirurg ; 117(1): 80-2, 2014 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-23756787

RESUMO

The irritating effects of concrete (calcium oxide) on skin have long been known. The effect by long-term skin exposure is not only irritating but also erosive and alkali skin erosion may result due to colliquative skin necrosis. A complicated course may ensue potentially necessitating plastic reconstructive treatment due to the development of unstable scars and defects. Correct interpretation of the skin trauma and adequate treatment are mandatory for functional restitution.


Assuntos
Álcalis/intoxicação , Queimaduras Químicas/cirurgia , Materiais de Construção/efeitos adversos , Dermatite Alérgica de Contato/cirurgia , Procedimentos Cirúrgicos Dermatológicos/métodos , Traumatismos da Perna/cirurgia , Pele/lesões , Adulto , Queimaduras Químicas/diagnóstico , Queimaduras Químicas/etiologia , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/etiologia , Humanos , Traumatismos da Perna/diagnóstico , Traumatismos da Perna/etiologia , Masculino , Resultado do Tratamento
12.
Br J Dermatol ; 168(6): 1205-14, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23252883

RESUMO

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune skin disease in which patient autoantibodies react with BP180 and BP230 proteins. In addition to IgG, IgE has been shown to play a role in the disease. OBJECTIVES: To evaluate the feasibility of detecting IgE and IgG against the immunodominant BP180 NC16A domain (BP180) using a microarray system. METHODS: BP180 was immobilized on an experimental version of the ISAC(®) microarray (Exp96). The BP study group and the controls were all tested on the commercial ISAC 103 version and on the Exp96. IgG and IgE were measured in a single run. BP180 IgG and IgE results were compared with those using an enzyme-linked immunosorbent assay (ELISA). RESULTS: All results obtained using the IgG ELISA on the 31 patients with BP were replicated with the ISAC IgG. Five of eight BP sera tested by ELISA showed similar results with ISAC IgE. Twenty-nine (94%) and 19 (61%) of the 31 patients with BP were IgG and IgE positive to BP180, respectively, whereas four (3%) and six (4%) of 138 normal donors were IgG and IgE positive, respectively. Interestingly, the levels of IgG against BP180 detected using the ISAC system were related to the disease severity. Patients with BP showed a peculiar profile of IgE recognition toward some groups of allergens, which was absent in a group of allergic individuals. A significant, higher prevalence of hen's egg recognition was observed in patients with BP who had specific IgE to BP180. CONCLUSIONS: The present preliminary study indicates that the ISAC microarray system is suitable for detecting IgG and IgE autoantibodies in patients with BP. Notably, this system allows the assessment of IgE and IgG autoantibodies at the same time, could be employed for the detection of autoantibodies to other autoantigens, and allows profiling for specific IgE to allergens.


Assuntos
Autoanticorpos/sangue , Autoantígenos/imunologia , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Colágenos não Fibrilares/imunologia , Penfigoide Bolhoso/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Lactente , Masculino , Análise em Microsséries/métodos , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem , Colágeno Tipo XVII
13.
Br J Dermatol ; 166(4): 844-52, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22092243

RESUMO

BACKGROUND: Pemphigus vulgaris (PV) is a potentially life-threatening autoimmune bullous disorder which is characterized by blisters and erosions of the skin and mucous membranes. A frequently applied first-line therapy for PV consists of systemic corticosteroids (CS) combined with immunosuppressive agents. In refractory cases, novel therapeutic strategies such as immunoadsorption (IA) and the anti-CD20 antibody rituximab (Rtx) aim at directly interfering with pathogenic autoantibodies (auto-Abs). OBJECTIVES: To investigate the long-term efficacy of IA in combination with Rtx in patients with difficult-to-treat PV, we assessed the clinical response to treatment by monitoring the Autoimmune Bullous Skin Disorder Intensity Score, IgG auto-Abs against desmoglein 1 and 3 (Dsg1 and Dsg3) and the dose of systemic CS. METHODS: We retrospectively analysed clinical and serological parameters of 10 patients with difficult-to-treat PV who received IA at 4-week intervals, followed by Rtx either twice at 1000 mg or four times at 375mg m(-2) . During a 12-month follow-up period, CS were tapered according to the individual clinical status. RESULTS: Six months after the first IA treatment eight of 10 patients were in complete remission on therapy while one patient showed a partial response and one patient was unresponsive to the treatment. At 12 months, six of eight patients were in complete remission on therapy, one patient showed stable disease and one patient had relapsed. Overall, anti-Dsg3 IgG and anti-Dsg1 IgG auto-Abs correlated well with the clinical activity and systemic CS were tapered gradually. CONCLUSIONS: The present findings show that the combination of IA and Rtx induces rapid clinical remission and long-term control in difficult-to-treat pemphigus.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Técnicas de Imunoadsorção , Pênfigo/terapia , Adulto , Idoso , Autoanticorpos/metabolismo , Doença Crônica , Terapia Combinada , Feminino , Humanos , Imunoglobulina G/metabolismo , Masculino , Pessoa de Meia-Idade , Pênfigo/sangue , Prednisolona , Indução de Remissão , Estudos Retrospectivos , Rituximab , Resultado do Tratamento
14.
Hautarzt ; 62(7): 524-33, 2011 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-21647771

RESUMO

Ulcerations of the skin and mucosal membranes are a common feature of autoinflammatory diseases. They can give raise to chronic wound healing defects and should be considered in the differential diagnosis of chronic skin ulcers. The increased activation of the innate immune system in the absence of an apparent provocation for inflammation is a hallmark of autoinflammatory diseases. Mutations and alterations of signaling pathways regulating the innate immune response to physical trauma/tissue damage result into an unrestrained activation of the inflammasome, which leads to increased activation of Interleukin-1. Uncontrolled recruitment and activation of myeloid effector cells within the wound site lead to the release of potent proteases that cause the degradation of structural components of the skin. The majority of these diseases respond well to immunosuppressive and immunomodulatory treatment regimes. Therapeutic resistance converts the acute inflammatory response into a chronic and non-resolving inflammatory process that leads to tissue degeneration. In this article we will focus on the review of those autoinflammatory diseases that often display ulcerative cutaneous and aphthous lesions including pyoderma gangrenosum, Behçet disease, PAPA syndrome and hyperimmunoglobulinemia D with periodic fever syndrome (HIDS). Furthermore, the article will be complemented by an overview of those inflammatory diseases that are associated with non-ulcerative cutaneous manifestations.


Assuntos
Doenças Hereditárias Autoinflamatórias/diagnóstico , Úlcera Cutânea/diagnóstico , Cicatrização/imunologia , Acne Vulgar/diagnóstico , Acne Vulgar/tratamento farmacológico , Acne Vulgar/genética , Acne Vulgar/imunologia , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/tratamento farmacológico , Artrite Infecciosa/genética , Artrite Infecciosa/imunologia , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamento farmacológico , Síndrome de Behçet/genética , Síndrome de Behçet/imunologia , Análise Mutacional de DNA , Diagnóstico Diferencial , Doenças Hereditárias Autoinflamatórias/tratamento farmacológico , Doenças Hereditárias Autoinflamatórias/genética , Doenças Hereditárias Autoinflamatórias/imunologia , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Inflamassomos/sangue , Interleucina-1/sangue , Deficiência de Mevalonato Quinase/diagnóstico , Deficiência de Mevalonato Quinase/tratamento farmacológico , Deficiência de Mevalonato Quinase/genética , Deficiência de Mevalonato Quinase/imunologia , Pioderma Gangrenoso/diagnóstico , Pioderma Gangrenoso/tratamento farmacológico , Pioderma Gangrenoso/genética , Pioderma Gangrenoso/imunologia , Úlcera Cutânea/tratamento farmacológico , Úlcera Cutânea/genética , Úlcera Cutânea/imunologia , Estomatite Aftosa/diagnóstico , Estomatite Aftosa/genética , Estomatite Aftosa/imunologia , Cicatrização/efeitos dos fármacos
15.
Hautarzt ; 59(10): 793-805, 2008 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-18779943

RESUMO

Basic insight into immune mechanisms, particularly the role and function of various immune cells and proinflammatory cytokines in the etiopathogenesis of inflammatory dermatoses and autoimmune skin disorders, has made possible the development of novel therapeutic strategies. Because of their properties as antigen presenting cells and progenitors of autoantibody-secreting plasma cells, B cells have a major impact in different autoimmune diseases and represent an important therapeutic target. The remarkable clinical improvement seen in patients with rheumatoid arthritis after treatment with the monoclonal anti-CD20 antibody, rituximab, has strongly augmented the interest in B-cell-targeted therapies in different autoimmune diseases. Future clinical and immunological investigations are mandatory to precisely define the contribution of impaired B-cell function in development and progression of autoimmune mediated skin disorders.


Assuntos
Anticorpos/imunologia , Linfócitos B/imunologia , Modelos Imunológicos , Dermatopatias/imunologia , Dermatopatias/patologia , Humanos
16.
Br J Dermatol ; 143(6): 1279-82, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11122034

RESUMO

BACKGROUND: Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are autoimmune bullous skin diseases mediated by autoantibodies against adhesion molecules of the skin. Previous studies have identified autoreactive T cells in patients with BP and PV, which may be critical in providing B-cell help for autoantibody production. OBJECTIVES: To evaluate the frequency of autoreactive T-helper (Th) 1 and Th2 cells in patients with BP (n = 7) or PV (n = 1) and in healthy controls (n = 11). METHODS: In an enzyme-linked immunospot (ELISPOT) assay, microtitre plates were coated with antihuman interleukin (IL)-5 IgG or antihuman interferon (IFN)-gamma IgG prior to culturing human peripheral blood lymphocytes (PBL) with BP180 or desmoglein (Dsg) 3 proteins for 7 days. Cytokine-producing autoreactive T cells were visualized as spot-forming units. RESULTS: One BP patient with extensive blisters had 5.1 +/- 1.5 (mean +/- SD) BP180-reactive Th1 cells and 2.9 +/- 1.5 Th2 cells per 105 PBL. In contrast, PBL from six BP patients in remission or on immunosuppressive therapy did not form IFN-gamma- or IL-5-producing spots per

Assuntos
Penfigoide Bolhoso/imunologia , Pênfigo/imunologia , Células Th1/imunologia , Células Th2/imunologia , Autoimunidade/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Humanos
17.
J Clin Invest ; 102(12): 2082-9, 1998 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-9854043

RESUMO

Antibodies against the extracellular domain of bullous pemphigoid antigen 2 (BPAG2) are thought to play a key role in the pathogenesis of bullous pemphigoid (BP), the most frequent autoimmune bullous disease of the skin. Autoreactive T cell responses to BPAG2 were investigated in 16 BP patients and 24 healthy controls by coculture of PBMC with two recombinant BPAG2 proteins (extracellular domain of BPAG2). Primary in vitro T cell responses to BPAG2 were observed in 10/12 BP patients expressing the BP-associated HLA-DQB1*0301 allele and 8/10 DQB1*0301 positive healthy individuals. DQB1*0301 also restricted three autoreactive T cell lines from two BP patients and a healthy donor. In contrast, PBMC from 14 normal patients carrying HLA class II alleles other than DQB1*0301 were not stimulated by BPAG2. Autoreactive BPAG2-specific CD4(+) T cell lines and clones from five BP patients produced both Th1 and Th2 cytokines, whereas three autoreactive T cell lines from three DQB1*0301 positive normal patients produced exclusively IFN-gamma. The absence of BPAG2-specific Th2 cells in healthy individuals strongly suggests that autoreactive Th2 responses to BPAG2 are restricted to BP patients and may thus be critical in the pathogenesis of BP.


Assuntos
Autoantígenos/imunologia , Doenças Autoimunes/imunologia , Proteínas de Transporte , Colágeno/imunologia , Proteínas do Citoesqueleto , Proteínas do Tecido Nervoso , Colágenos não Fibrilares , Penfigoide Bolhoso/imunologia , Pele/imunologia , Linfócitos T/imunologia , Adulto , Idoso , Linfócitos T CD4-Positivos/imunologia , Divisão Celular/imunologia , Células Cultivadas , Células Clonais/imunologia , Citocinas/imunologia , Distonina , Citometria de Fluxo , Antígenos HLA-DQ/imunologia , Cadeias beta de HLA-DQ , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Pessoa de Meia-Idade , Proteínas Recombinantes/imunologia , Células Th1/imunologia , Células Th2/imunologia , Colágeno Tipo XVII
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