RESUMO
The Swiss National Registry for Primary Immunodeficiency Disorders (PID) was established in 2008, constituting a nationwide network of paediatric and adult departments involved in the care of patients with PID at university medical centres, affiliated teaching hospitals and medical institutions. The registry collects anonymized clinical and genetic information on PID patients and is set up within the framework of the European database for PID, run by the European Society of Immunodeficiency Diseases. To date, a total of 348 patients are registered in Switzerland, indicating an estimated minimal prevalence of 4·2 patients per 100 000 inhabitants. Distribution of different PID categories, age and gender are similar to the European cohort of currently 19 091 registered patients: 'predominantly antibody disorders' are the most common diseases observed (n = 217/348, 62%), followed by 'phagocytic disorders' (n = 31/348, 9%). As expected, 'predominantly antibody disorders' are more prevalent in adults than in children (78 versus 31%). Within this category, 'common variable immunodeficiency disorder' (CVID) is the most prevalent PID (n = 98/217, 45%), followed by 'other hypogammaglobulinaemias' (i.e. a group of non-classified hypogammaglobulinaemias) (n = 54/217, 25%). Among 'phagocytic disorders', 'chronic granulomatous disease' is the most prevalent PID (n = 27/31, 87%). The diagnostic delay between onset of symptoms and diagnosis is high, with a median of 6 years for CVID and more than 3 years for 'other hypogammaglobulinaemias'.
Assuntos
Agamaglobulinemia/epidemiologia , Imunodeficiência de Variável Comum/epidemiologia , Bases de Dados Factuais/estatística & dados numéricos , Disfunção de Fagócito Bactericida/epidemiologia , Sistema de Registros/estatística & dados numéricos , Adulto , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/genética , Criança , Imunodeficiência de Variável Comum/diagnóstico , Imunodeficiência de Variável Comum/genética , Diagnóstico Tardio/estatística & dados numéricos , Feminino , Humanos , Masculino , Disfunção de Fagócito Bactericida/diagnóstico , Disfunção de Fagócito Bactericida/genética , Suíça/epidemiologiaRESUMO
The anti-synthetases syndrome is a rare disease with a specific constellation of clinical symptoms present in a subset of patients with inflammatory myopathy. Besides constitutional symptoms and myositis, it is associated with mechanic's hands, Raynaud phenomenon, and non-erosive arthritis. This syndrome is characterized by the presence of one of eight auto-antibodies to aminoacyl-transfer ribonucleic acid synthetase enzymes in the serum. Interstitial lung disease is more frequent in this subpopulation of inflammatory myopathy and worsens the patient's prognosis.
Assuntos
Autoanticorpos/imunologia , Doenças Pulmonares Intersticiais/etiologia , Miosite/terapia , Adulto , Humanos , Doenças Pulmonares Intersticiais/epidemiologia , Masculino , Miosite/diagnóstico , Miosite/fisiopatologia , PrognósticoRESUMO
Long-term insulin independence after islets of Langerhans transplantation is rarely achieved. The aims of this study were to identify the histological and immunological features of islets transplanted in a type 1 diabetic patient who died of a cerebral hemorrhage after >13 years insulin independence. Islets were pooled from two donors with respectively one and five HLA mismatches. Insulin-positive islets were found throughout the right and left liver, and absent in the pancreas. Two- and three-dimensional analysis showed that islets lost their initial rounded and compact morphology, had a mean diameter of 136 µm and were constituted of an unfolded epithelial band of 39.1 µm. Leukocyte phenotyping showed no evidence of a tolerogenic environment in the islet-containing portal spaces. Finally, HLA typing of microdissected islets showed HLA from the best matched donor in all 23 microdissection samples, compared to 1/23 for the least matched donor. This case report demonstrates that allogeneic islets can survive over 13 years while maintaining insulin independence. Allogeneic islets had unique morphologic features and implanted in the liver regardless of their size. Finally, our results suggest that, in this case, rejection had been prevalent over autoimmunity, although this hypothesis warrants further investigation.
Assuntos
Diabetes Mellitus Tipo 1/terapia , Insulina/uso terapêutico , Transplante das Ilhotas Pancreáticas/métodos , Adulto , Autoimunidade , Feminino , Antígenos HLA/química , Cadeias HLA-DRB1/genética , Humanos , Sistema Imunitário , Células Secretoras de Insulina/citologia , Transplante de Rim/métodos , Leucócitos/citologia , Fígado/patologia , Microscopia de Fluorescência , Pâncreas/patologia , Fenótipo , Reação em Cadeia da Polimerase , Resultado do TratamentoRESUMO
Involvement of the central or peripheral nervous system, frequently present in systemic inflammatory immune disorders, has to be considered a severe threat and requires aggressive immunosuppressive treatment to achieve rapid remission. This is usually obtained with high-dose systemic corticosteroids combined with cyclophosphamide. Once remission is obtained, immunosuppressive agents with a more favorable safety profile are needed to exert a corticosteroid-sparing effect and minimize adverse events. New therapeutic approaches are currently developed to treat autoimmune diseases, mostly linked to the definition of new indications for biological agents such as TNF-alpha antagonists and rituximab.
Assuntos
Imunossupressores/uso terapêutico , Doenças do Sistema Nervoso/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Linfócitos B/imunologia , Humanos , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
Antiseptics are widely used in medical practice. Their cutaneous secondary effects such as allergic contact dermatitis are well known. However, anaphylactic reactions are less. The scope of this article is to describe antiseptics currently used which cause immediate hypersensitivity reactions. Finally, the diagnostic tools and therapeutic approach will be discussed.
Assuntos
Anafilaxia/induzido quimicamente , Anti-Infecciosos Locais/efeitos adversos , Humanos , Testes CutâneosRESUMO
US11 and US2 encode gene products expressed early in the replicative cycle of human cytomegalovirus (HCMV), which cause dislocation of human and murine major histocompatibility complex (MHC) class I molecules from the lumen of the endoplasmic reticulum to the cytosol, where the class I heavy chains are rapidly degraded. Human histocompatibility leukocyte antigens (HLA)-C and HLA-G are uniquely resistant to the effects of both US11 and US2 in a human trophoblast cell line as well as in porcine endothelial cells stably transfected with human class I genes. Dislocation and degradation of MHC class I heavy chains do not appear to involve cell type-specific factors, as US11 and US2 are fully active in this xenogeneic model. Importantly, trophoblasts HLA-G and HLA-C possess unique characteristics that allow their escape from HCMV-associated MHC class I degradation. Trophoblast class I molecules could serve not only to block recognition by natural killer cells, but also to guide virus-specific HLA-C- and possibly HLA-G-restricted cytotoxic T-lymphocytes to their targets.
Assuntos
Citomegalovirus/imunologia , Antígenos HLA/biossíntese , Antígenos HLA-C/biossíntese , Antígenos de Histocompatibilidade Classe I/biossíntese , Trofoblastos/metabolismo , Animais , Linhagem Celular Transformada , Citomegalovirus/genética , Endotélio Vascular , Antígenos H-2/imunologia , Antígenos HLA/genética , Antígenos HLA-C/genética , Antígenos HLA-G , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/imunologia , Suínos , Trofoblastos/imunologia , Células Tumorais Cultivadas , Proteínas Virais/genética , Proteínas Virais/imunologia , Microglobulina beta-2/imunologiaRESUMO
ABO-incompatible kidney transplantation using immunoadsorption to remove anti-A/B antibodies has become a successful clinical practice. Since the data on the specificity of the ABO columns are controversial, the present study assessed the efficiency and specificity of the ABO immunoadsorption, the effect on total immunoglobulins and antibodies previously induced by vaccination. Anti-A/B antibodies were measured by agglutination and ABO flow cytometry, total IgG/IgM, carbohydrate- and protein-specific antibodies by nephelometry and ELISA. The first immunoadsorption not only efficiently reduced donor-specific anti-A/B IgM (81%) and IgG (56%) but also reduced compatible anti-A/B IgM (59%) and IgG (34%). The measurements of antidonor A/B antibodies by direct agglutination (IgM) or flow cytometry better represented the effective antibody levels than the indirect agglutination test (IgG). The median reduction of total IgM and total IgG levels after a single immunoadsorption was 34% and 18%, respectively. Antibodies against pneumococcus and haemophilus polysaccharide antigens were significantly reduced, whereas antitetanus and antidiphtheria protein antibodies were not affected. Intravenous immunoglobulin administration restored the protective anticarbohydrate antibody levels. In summary, immunoadsorption efficiently removed antidonor A/B antibodies, but was not specific for A/B antigens. Anti-A/B antibody levels as determined by ABO flow cytometry are useful to establish the minimal number of immunoadsorptions needed for successful ABO-incompatible transplantation.
Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos , Isoanticorpos/sangue , Transplante de Rim/imunologia , Adulto , Incompatibilidade de Grupos Sanguíneos/imunologia , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Testes de Hemaglutinação , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemAssuntos
Eosinofilia/induzido quimicamente , Inibidores da Agregação Plaquetária/efeitos adversos , Ticlopidina/análogos & derivados , Clopidogrel , Doença da Artéria Coronariana/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagem , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversosRESUMO
Cytomegalovirus (CMV) infection is the most common viral complication after solid organ transplantation (SOT). Whilst current immunosuppression is known to impair antiviral-specific T-cell immunity in SOT, a potential role for natural killer (NK) cells not affected by immunosuppressive therapy remains to be determined. To address this, we compared the genotype of the NK immunoglobulin-like receptor (KIR) genes and their HLA cognate ligands to the rate of CMV infection in 196 kidney transplant recipients. We have shown that the absence of the HLA-C ligand for inhibitory KIR and the presence of activating KIR genes in the recipients were both associated with a lower rate of CMV infection after transplantation. In a cohort of 17 recipients with acute CMV infection, NK cells were phenotyped over a period of time after diagnosis by their expression profile of C-type lectin receptors and capacity to secrete IFN-gamma. The increased expression of the activating C-type lectin receptors NKG2C and NKG2D was paralleled by the decreased IFN-gamma secretion during the early phase of CMV infection. In conclusion, our findings suggest that KIR/HLA genotype and expression of NKG2C and NKG2D might play a significant role in regulating NK cell function and anti-CMV immunity after kidney transplantation.
Assuntos
Infecções por Citomegalovirus/epidemiologia , Transplante de Rim , Lectinas Tipo C/metabolismo , Complicações Pós-Operatórias , Receptores de Células Matadoras Naturais/metabolismo , Adulto , Citomegalovirus/imunologia , Infecções por Citomegalovirus/imunologia , Feminino , Genótipo , Antígenos HLA-C/genética , Antígenos HLA-C/metabolismo , Humanos , Interferon gama/metabolismo , Transplante de Rim/imunologia , Células Matadoras Naturais/fisiologia , Lectinas Tipo C/genética , Ligantes , Masculino , Pessoa de Meia-Idade , Subfamília C de Receptores Semelhantes a Lectina de Células NK/genética , Subfamília C de Receptores Semelhantes a Lectina de Células NK/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Receptores KIR/genética , Receptores KIR/metabolismo , Receptores de Células Matadoras Naturais/genética , Estudos Retrospectivos , Fatores de RiscoRESUMO
Pathogenesis of viral haemorrhagic fever (VHF) is closely associated with alterations of the vascular system. Among the virus families causing VHF, filoviruses (Marburg and Ebola) are the most fatal, and will be focused on here. After entering the body, Ebola primarily targets monocytes/macrophages and dendritic cells. Infected dendritic cells are largely impaired in their activation potency, likely contributing to the immune suppression that occurs during filovirus infection. Monocytes/macrophages, however, immediately activate after viral contact and release reasonable amounts of cytokines that target the vascular system, particularly the endothelial cells. Some underlying molecular mechanisms such as alteration of the vascular endothelial cadherin/catenin complex, tyrosine phosphorylation, expression of cell adhesion molecules, tissue factor and the effect of soluble viral proteins released from infected cells to the blood stream will be discussed.
Assuntos
Febres Hemorrágicas Virais/sangue , Arenavirus/patogenicidade , Endotélio Vascular/fisiopatologia , Filoviridae/patogenicidade , Flavivirus/patogenicidade , Febres Hemorrágicas Virais/virologia , Humanos , Peróxido de Hidrogênio/sangue , Orthobunyavirus/patogenicidade , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
In contrast to solid organ transplantation, ABO incompatibility is generally not associated with survival differences in hematopoietic stem cell transplantation. Therefore, patients receiving ABO-incompatible stem cell transplantation can be analyzed to study the mechanism of tolerance induction after antigen-mismatched transplantation. The goal of this study was to analyze the levels of anti-A/B antibodies after ABO-incompatible transplantation. Host-derived antidonor antibodies disappeared rapidly after transplantation and did not reappear in the further posttransplant course. Donor-derived antihost antibodies did not significantly increase and compatible anti-A/B antibodies remained positive after hematopoietic stem cell transplantation. Thus, there is no evidence for stimulation of donor B lymphocytes to produce antirecipient antibodies suggesting a potential B cell tolerance.
Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Transplante de Células-Tronco/efeitos adversos , Anemia Aplástica/imunologia , Anemia Aplástica/terapia , Incompatibilidade de Grupos Sanguíneos/etiologia , Eritrócitos/imunologia , Reação Enxerto-Hospedeiro/imunologia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/terapia , Reação Hospedeiro-Enxerto/imunologia , HumanosAssuntos
Controle de Doenças Transmissíveis/métodos , Doenças Transmissíveis , Transmissão de Doença Infecciosa/prevenção & controle , Doença Crônica , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/etiologia , Doenças Transmissíveis/microbiologia , Doenças Transmissíveis/virologia , Progressão da Doença , Humanos , Hipersensibilidade/diagnóstico , Esquemas de Imunização , Hospedeiro Imunocomprometido , Vacinação/métodosRESUMO
Ammonium-chloride-containing solutions (AC) are routinely used to lyse red blood cells during preparation of PBMC. Although exposure to AC has been described to affect the ultrastructural appearance of large granular lymphocytes and to temporarily inhibit cytolytic activity of PBMC preparations, the cellular basis of this phenomenon has not been studied. Here, the inhibitory effect of AC on human CTL and NK-mediated cytotoxicity has been analyzed in 4-h 51Cr-release assays. The results show that NK killing of K562 leukemia cells and xenogeneic endothelial cells is inhibited by AC exposure. The effect is dose-dependent and reversible, because recovery of cytotoxicity is observed within 15 h of re-culturing. AC does not reduce the viability of NK cells and the inhibitory effect is not mediated by the exhaustive release of granzymes upon AC treatment. In contrast, antigen-specific CTL killing of EBV-transformed B-lymphoblastoid cell lines and xenogeneic PHA lymphoblasts was less sensitive to AC and data are presented suggesting that FasL-induced apoptosis is not inhibited by AC. In conclusion, perforin-mediated NK killing is AC-sensitive whereas CTL killing and FasL-mediated killing appear to be AC-resistant. Therefore, AC represents a powerful tool to study different mechanisms of cell-mediated cytotoxicity and may be helpful in assessing antigen-specific CTL cytotoxicity without the influence of NK cell-mediated background killing.
Assuntos
Cloreto de Amônio/farmacologia , Citotoxicidade Imunológica/efeitos dos fármacos , Células Matadoras Naturais/efeitos dos fármacos , Glicoproteínas de Membrana/imunologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Citotoxicidade Celular Dependente de Anticorpos/efeitos dos fármacos , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Degranulação Celular/efeitos dos fármacos , Linhagem Celular Transformada , Citotoxicidade Imunológica/imunologia , Proteína Ligante Fas , Humanos , Células K562 , Células Matadoras Ativadas por Linfocina/efeitos dos fármacos , Células Matadoras Ativadas por Linfocina/imunologia , Células Matadoras Naturais/imunologia , Cinética , Perforina , Proteínas Citotóxicas Formadoras de Poros , Linfócitos T Citotóxicos/imunologiaRESUMO
Chemokines constitute a constantly growing family of small inflammatory cytokines. They have been implied in many different diseases of the CNS including trauma, stroke and inflammation, e.g., multiple sclerosis. In this review we focus on the role of chemokines in infectious meningitis of bacterial or viral origin. In experimental bacterial meningitis induced by Listeria monocytogeneses both CXC and CC chemokines namely MIP-1alpha, MIP-1beta and MIP-2 are produced intrathecally by meningeal macrophages and leukocytes which infiltrate into the CNS. In patients with bacterial meningitis, IL-8, GROalpha, MCP-1, MIP-1alpha and MIP-1beta are detectable in the CSF. These chemokines contribute to CSF mediated chemotaxis on neutrophils and PBMC in vitro. In viral meningitis IL-8, IP-10 and MCP-1 are identified in the CSF to be responsible for chemotactic activity on neutrophils, PBMC and activated T cells. Taken collectively these data indicate that the recruitment of leukocytes in infectious meningitis involves the intrathecal production of chemokines.
Assuntos
Quimiocinas/fisiologia , Quimiotaxia de Leucócito/fisiologia , Meningites Bacterianas/fisiopatologia , Meningite Viral/fisiopatologia , Humanos , Mediadores da Inflamação/fisiologia , Meningites Bacterianas/líquido cefalorraquidiano , Meningite Viral/líquido cefalorraquidiano , Metaloendopeptidases/fisiologiaRESUMO
BACKGROUND: In this study, we describe the development of a novel experimental system in which rejection of porcine skin grafts by human peripheral blood cells can be studied directly in vivo in immunodeficient mice. METHODS: To construct a small animal model of discordant xenograft rejection, recombinase-activating gene-deficient mice (R-) lacking both mature B and T cells were grafted with porcine skin grafts and administered, by adoptive cell transfer, human cells stimulated in vitro with irradiated porcine peripheral blood cells to create Hu-R- mice. RESULTS: R- mice accepted porcine skin grafts indefinitely without the need for immunosuppression. In contrast, Hu-R- mice were able to reject porcine skin grafts. Immunohistochemical analysis of rejecting skin grafts revealed the accumulation of human T cells around dermal porcine vessels and focally in the epidermis. Graft rejection was manifested by vascular endothelial cell proliferation, edema at the dermal-epidermal border, and perivascular hemorrhage. The tissue damage observed in the rejecting grafts was similar to that observed in delayed primate anti-porcine cell-mediated rejection of vascularized organ xenografts. CONCLUSIONS: The development and characterization of a small animal model, to study cellular immune responses of human cells to discordant xenografts in vivo, should provide a convenient means for asking mechanistic questions related to discordant xenotransplantation, and may also provide a practical system for testing new approaches designed to prevent xenograft rejection.