RESUMO
UNLABELLED: The development of inhibitors in haemophilia B is one of the most important complications of replacement therapy, affecting mortality and morbidity. Inhibitor development is based on complex immunological factors, and to date, only little is known about its underlying mechanisms. Here, we present first results of the haemophilia B group of our Inhibitor-Immunology study. PATIENTS, METHODS: So far we have analysed 15 patients with haemophilia B. Four of them developed a high titre inhibitor; the remaining 11 had no inhibitor. We evaluated 9 SNPs in 8 genes (CD40, CTLA-4 , IL-1ß, IL-10, TLR2 , TLR4, TLR9, TNF-α). We compared the distribution of these alleles between inhibitor and non-inhibitor haemophilia B patients and between haemophilia B patients and a normal male control population. HLA typing was performed in all patients. Results, discussion: There appears to be a trend towards a skewed distribution of TLR 9, IL-10 and CTLA4 alleles in haemophilia B patients. Due to the limited number these differences are, however, not statistically significant. The t-test of all patients with inhibitor versus without inhibitor was significant for HLA-A*03 and DPB1*0401 and borderline for DRB1*0201.
Assuntos
Inibidores dos Fatores de Coagulação Sanguínea/sangue , Inibidores dos Fatores de Coagulação Sanguínea/genética , Genes MHC da Classe II/genética , Predisposição Genética para Doença/genética , Hemofilia B/sangue , Hemofilia B/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Adulto JovemRESUMO
UNLABELLED: The development of inhibitors is one of the most important complications of replacement therapy in haemophilia, affecting mortality and morbidity. Inhibitor development is based on complex immunological factors. Cytokines and their receptors, T-cell receptors, and the Major Histocompatibility Complex may play important roles in the development of inhibitors. Earlier studies showed non significant associations between HLA class and inhibitor development. Later studies found an increased risk of inhibitor development if there was a combination between certain factor VIII mutations and HLA antigens. We performed HLA typing in 50 patients with haemophilia A in an effort to find associations with inhibitor development. RESULTS: 25 patients had developed an inhibitor (11 low titre, 14 high titre), and 25 never had. In logistic regression analysis, HLA-A 34, DRB1 0405, DRB1 1301 seemed to be involved in inhibitor development and HLA-A 30, B 13, B15, B 57, Cw 12, DQB1 0303, DPB1 0201 protection against inhibitor development. In our patients, the HLA-associations with inhibitor development were different from those in previous publications.
Assuntos
Antígenos HLA/imunologia , Hemofilia A/imunologia , Etnicidade , Fator VIII/genética , Fator VIII/imunologia , Antígenos HLA/genética , Antígenos HLA-A/genética , Antígenos HLA-A/imunologia , Antígenos HLA-B/genética , Antígenos HLA-B/imunologia , Antígenos HLA-DR/genética , Antígenos HLA-DR/imunologia , Cadeias HLA-DRB1 , Hemofilia A/genética , Hemofilia A/prevenção & controle , Hemofilia B/imunologia , Hemofilia B/prevenção & controle , Teste de Histocompatibilidade , Humanos , Isoanticorpos/genética , Isoanticorpos/imunologia , Mutação , Análise de RegressãoRESUMO
The objective of this study is to evaluate complications and changes in health status (disease activity and flare) in response to the AS03-adjuvanted H1N1 vaccine in children with rheumatic diseases. We conducted a nationwide survey addressing paediatric rheumatology sites who participated in the national paediatric rheumatology database. Ninety patients were documented-38 % under treatment with biologicals-of whom 18 % suffered from complications (10 % local and 8 % systemic) with no relevant changes in median disease activity or flare rate during 4 weeks following the vaccination. The adjuvanted H1N1 influenza vaccine seems to be adequately tolerated in children with rheumatic diseases.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Doenças Reumáticas/complicações , Doenças Reumáticas/imunologia , Adolescente , Antirreumáticos/uso terapêutico , Artrite Juvenil/complicações , Artrite Juvenil/tratamento farmacológico , Autoanticorpos/química , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Alemanha , Nível de Saúde , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/imunologia , Masculino , Metotrexato/uso terapêutico , Reumatologia/normas , Inquéritos e Questionários , VacinaçãoRESUMO
Inherited disorders of platelet function are a heterogeneous group. For optimal prevention and management of bleeding, classification and diagnosis of the underlying defect are highly recommended. An interdisciplinary guideline for a diagnostic approach has been published (AWMF # 086-003 S2K; Hämostaseologie 2014; 34: 201-212). Underlying platelet disorder, platelet count, age and clinical situation modify treatment. Exclusive transfusion of platelet concentrates may be inappropriate as potentially adverse effects can outweigh its benefit. A stepwise and individually adjusted approach for restitution and maintenance of haemostasis is recommended. Administration of antifibrinolytics is generally endorsed, but is of particular use in Quebec disease. Restricted to older children, desmopressin is favourable in storage pool disease and unclassified platelet disorders. Although licensed only for patients with Glanzmann thrombasthenia and alloantibodies, in clinical practice rFVIIa is widely used in inherited platelet disorders with severe bleeding tendency. This guideline aims at presenting the best available advice for the management of patients with inherited platelet function disorders.