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In addition to providing multidisciplinary care for patients of all ages who suffer this condition, the objectives of Vall d’Hebron Hospital’s Hereditary Angioedema Unit include teaching and research in this field.
The Hereditary Angioedema Unit (UAEH) of Vall d’Hebron University Hospital’s Allergology Department has been treating patients with this disorder for more than 25 years.
UAEH outpatients are treated by allergology specialists in a multidisciplinary manner in the Outpatient Clinic in the Old Nursing School and in the Children’s and Women’s Hospital, ensuring transference and continuity of care from childhood through to adulthood for this genetic, lifelong condition.
The Unit is made up of popular, immunologists, geneticists, gynaecologists, maxillofacial surgeons, pharmacists and nurses, who are responsible for:
Depending on the type of care to be given to patients with diagnosed hereditary angioedema and their profile, they should be treated by the following divisions and/or units:
The specialists who work in the adult and paediatric allergology sections are responsible for treating patients aged 16 and under in the Children’s Hospital areas and subsequently facilitating their transfer and continuity of care with monitoring to the adult care departments in the Old Nursing School and the Allergology Day Hospital in the General Hospital.
The Hereditary Angioedema Unit (UAEH) offers an outpatient service to monitor patients with this disease: the Outpatient Clinic on the second floor of the Old Nursing School. Also, as it is a multidisciplinary unit, and depending on the type of patient (child, adult, pregnant woman), it provides care in a number of departments and units in the Children’s and Women’s Hospital, the General Hospital and A&E.
The nursing team specialises in education and specific care for patients with this disease.
Emergency care is provided at the Children’s Hospital for patients up to the age of 16 and at the General Hospital from the age of 17. The professionals who work in the A&Es have been trained to recognise the symptoms of this disease and to quickly provide its specific treatment.
When a patient needs a complex dental or maxillofacial procedure they will be assessed by the hospital’s maxillofacial surgeons and their operation will be organised with the suitable prophylaxis.
The Obstetrics, Foetal Medicine and Anaesthesia Departments have created a Working Unit for High-Risk Pregnancies for women with hereditary angioedema with the aim of monitoring the well-being of mother and child during pregnancy and of providing care during the delivery and postpartum period in accordance with a protocol specific to their type of hereditary angioedema and clinical situation. Care is also provided for high-risk postpartum cases.
In parallel to these services, there is also a reproductive counselling clinic for women with hereditary angioedema. The clinic is part of the Hereditary Angioedema Unit, and is that provided in conjunction with Gynaecology in the Outpatient Clinics of the Children’s and Women’s Hospital.
In this clinic an allergist and a gynaecologist combine their expertise to determine, in accordance with the patient’s clinical situation and type of hereditary angioedema, the possible effects of their having children. Their mission is to provide information and advice in relation to family planning and the reproductive possibilities of the patients living with this disease.
The Immunology Department performs routine and complex immune system diagnostic tests, assessing and interpreting them in a clinical context. For complex testing, we act as a reference laboratory for other Catalan Health Institute centres when these centres request our help.
Most healthcare activities consist of diagnostic testing, and assessment and opinion, where applicable. Within this practice, we provide direct and continuous advice to clinical practitioners, by email, telephone as well as in person. We also design and improve diagnostic tests and protocols that allow diagnostic methods to be continually updated and bring clinical services into line with clinical requirements. Teaching and research are both crucial for the work that we are doing.
Our department includes a clinical immunology outpatients unit in which the diagnosis and follow-up of patients affected by adult immunodeficiency or immune complex pathophysiology is performed. Evaluation of the immune system’s response capacity is crucial to this activity. This unit is complementary to the Infectious Pathology and Immunodeficiencies Unit of the Paediatrics Department and the Bronchiectasis and Cystic Fibrosis Unit in the Pneumology Department.
It also actively takes part in clinical procedures within the hospital, in multidisciplinary approaches to amyloidosis, multiple myeloma, primary immunodeficiency and complex kidney diseases, as well as in the Advanced Haematology Therapies Unit.It is a reference centre, forming part of the European Reference Network on Rare Primary Immunodeficiency, Autoinflammatory and Autoimmune disease (ERN-RITA) and the European Reference Network for Rare Kidney Diseases (ERK-Net). It is also part of the reference unit of the Neonatal Screening Programme of the Catalan Department of Health in the field of serious combined immunodeficiency (unique in Spain).
We investigate, develop and innovate through projects in the fields of primary immunodeficiency, autoimmunity and counselling in the design and execution of research projects conducted by other groups in the hospital. We actively work alongside other departments, especially Paediatrics (Paediatric Infectious Pathology and Immunodeficiency Unit), Medicine (Allergology, Rheumatology, Systemic Medicine) and Nephrology, which is concerned with kidney infections.
Our department participates in networks to improve diagnosis and investigation in immunology, directly in collaboration with other departments and through the Catalan Immunology Society and the Spanish Immunology Society.
In recognition of our work in the promotion of Translational Immunology in our centre, i.e. applied study in patients, the Federation of Clinical Immunology Societies (FOCIS) has named the Immunology Department as Vall d'Hebron University Hospital’s Barcelona-UAB-FOCIS Centre of Excellencecoordinator www.focisnet.org.
We have also established intense bilateral relations and shared projects with, among others, the following centres:
The Immunology Department laboratories have ISO 9001 certification, as do the hospital’s other clinical laboratories.
The Immunology Department has a broad, up-to-date portfolio of diagnostic services that responds to the majority of hospital patients’ needs and those of the hospital catchment area.
The main components studied are immunoglobins, complement and regulatory proteins common to the complement and coagulation cascades. To evaluate immune response in patients with suspected immunodeficiency, the levels of immunoglobulins are measured and characterised: classes, subclasses, monoclonal components, cryoglobulins and free chains, as well as the production of IgG antibodies against polysaccharide and peptide antigens.
Complement activity along the traditional and alternative pathways is measured, as well as the main components C3, C4, C1q and C1 inhibitor. If the departments request them, special studies are conducted to measure the function of other complement pathways and the other components that make up the complement, as well as its regulatory factors.
Molecular studies have also been carried out that serve to diagnose patients with hereditary angioedema (SERPING1 and F12), patients with infections from encapsulated microorganisms (C5 and C2) and patients with abnormalities due to reduction in immune complexes (C4 haplotypes).
The laboratory has modern capillary electrophoresis, immunofixation and isoelectric focusing equipment. It also has a huge catalogue of disease samples and a digital file of cases of patients with monoclonal gammopathy, cryoglobulinaemia, etc.
This section is dedicated to the study of primary and secondary immunodeficiency, including HIV infection (secondary immunodeficiency), the results of treatment with depletion and immunomodulating agents and transplant of blood stem cells.
With this in mind, the following are conducted:
Phenotype studies and quantitative analysis of the main lymphocyte populations (T CD4+, T CD8+, NK and B lymphocytes) through flow cytometry applied above all to monitoring patients.
Phenotype studies aimed at diagnosing primary immunodeficiency by assessing naive and memory T cells (CD45RO/RA), degree of activation (CD3/HLA-DR/CD25/CD69) and minority T and NK populations such as γδ and NKT. We work with standardised panels following the FITMaN protocol (Flow Immunophenotyping Technical Meeting at NIH), which allows 30 subgroups of T, B and NK cells, monocytes and dendrites to be studied at the same time.
Research into lymphocyte function, in which the proliferation capacity, the production of cytokines, activation markers and the oxidative and cytolytic capacity of the different cell populations are assessed.
Should haemophagocytic syndromes be diagnosed, cytotoxic NK activity is studied, along with degranulation capacity, through the analysis of CD107a expression in NK cells and CD8, as well as perforin expression.
When it comes to diagnosis and monitoring of phagocytosis defects, an oxidation test and a reduction in ferricytochrome C, tests aimed at diagnosing chronic granulomatous disease, are conducted.
The department has two flow cytometers with two and three lasers respectively, with an automatic sample processing and preparation system, and the corresponding IT analysis programmes. There is also a full installation for cell cultures and another to process level 3 radioactive samples.
The Immunology Department, in collaboration with the genetics department, has a catalogue of 300 genetic studies for the diagnosis of primary immunodeficiency. These studies include severe combined immunodeficiency (SCID), antibody disorders, familial haemophagocytic lymphohistiocytosis (FHLH), innate immune defects and the main complement deficiencies.
In order to provide a highly specialised service, functional tests on the proteins associated with primary immunodeficiency are conducted using western blot or flow cytometry tests. Studies can confirm that gene mutations are pathogenic and affect the proteins they codify.
This section examines alleles and/or haplotypes associated with diseases (coeliac, ankylosing spondylitis, Behçet's disease, narcolepsy and others) and hypersensitivity to drugs (Abacavir).
The Allergy Section performs tests aimed at identifying the allergies that cause hypersensitive reactions due to IgE or IgG. The Allergy Division establishes total IgE, as well as specific IgE versus allergens originating from food and inhaled allergens of different origins, both animal and vegetable (mites, pollen, grasses, epithelial tissues of animal origin, etc.). In total there is evidence to measure specific IgEs against more than 250 allergens.
Levels of tryptase in the blood are also measured to diagnose anaphylaxis.
A group of inhaled allergens of avian or fungal origin (for example, Aspergillus fumigatus), can cause allergic pneumonitis, with a possible evolution into severe pulmonary disease. The determination of specific IgGs versus these allergens contributes to the diagnosis of this group of conditions.
The Allergy Area has Phadia 1000 and Phadia 250 equipment to automatically conduct daily allergy testing. It is anticipated that we will soon be getting ImmunoCAP ISAC technology to determine the specific IgEs against 103 allergens, indicated in polysensitised patients.
The Autoimmune Section supports the diagnosis and monitoring of autoimmune diseases, both those specific to particular organs (such as myasthenia gravis, type I diabetes, autoimmune hepatitis, etc.) and systemic diseases (such as LES, SS and scleroderma).
The screening and characterisation of antinuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA) are performed. Anti-dsDNA antibodies, anti-cyclic citrullinated peptide and anti-transglutaminase antibodies are determined, required for the monitoring and diagnosis of systemic lupus erythematosus, rheumatoid arthritis and coeliac disease, respectively. In total there are techniques to determine autoantibodies against more than 100 antigenic specificities.
The section has equipment to automate the assembly and reading process of indirect immunofluorescence preparations, as well as specialised staff trained to read the microscope and interpret ANA, ANCA and anti-tissue immunofluorescence patterns. It also has robots for the ELISA chemiluminescent assay and immunotransfer technique for the characterisation and quantification of the different antigenic specificities. It holds an image library and collections of positive samples.
An inter-departmental functional unit that interacts with other sections in the department (immunoproteins, cell immunology, autoimmune diseases, etc.). Its objective is to monitor concentration of the biological drug, determine the presence of antibodies against the drug, study the presence of adverse effects and assess the action of the drug at the level of the immune response.
There is a catalogue of rapid response tests (response time <6 hours) in the laboratory, including Acs. Antineutrophil cytoplasmic antibodies (ANCA) for the diagnosis and monitoring of ANCA vasculitis, Acs. Antiphospholipids for catastrophic antiphospholipid syndrome, IL-6 concentration in serum for patients with sepsis or with cytokine release syndrome after treatment with immunotherapy, concentration of IL-6 in amniotic fluid in pregnant women suspected of subclinical chorioamnionitis, serum levels of soluble CD25 in patients with haemophagocytic lymphohistiocytosis and concentration of serum free chains in patients with suspected myeloma kidney.
Diagnosis and follow-up of patients affected by adult immunodeficiency or immune complex pathophysiology is performed. Evaluation of the immune system’s response capacity is crucial to this activity. The outpatient department monitors more than 200 patients and studies 100 new cases every year. There is a transition protocol to incorporate patients being treated by paediatrics when they reach adulthood. Consultation is based on specialised pneumology and digestive tract units, and the day hospital for treatment with intravenous immunoglobulins. Patients are also trained in how to self-administer endovenous immunoglobulins.
The Immunology Department is responsible for diagnosis, teaching and research in Immunology at Vall d'Hebron University Hospital (HUVH) and its catchment area. The key processes it performs are: Immunology diagnostic tests and in the design of diagnostic protocols, clinical immunology outpatient clinic, specialised teaching of immunology, pre- and postgraduate, and research, development and innovation through their own projects in the fields of primary immunodeficiencies, autoimmunity and consulting in the design and execution of the research projects of other groups in the Hospital.
Immunology training itinerary
The Immunology Department is part of VH Clinical Laboratories, some of the largest in Europe with more than 16,000,000 determinations / year. It is located in new premises (2014) on the ground floor of the VH Clinical Laboratories building (approximately 400 m2). It is organised by processes under the framework of the ISO 9001 quality management system: Autoimmunity, Hypersensitivity, Cellular Immunology, Immunogenetics (HLA and disease), Immunogenetics (Study of primary immunodeficiencies), Immunoproteins, Monitoring of immunotherapy and Clinical Immunology Clinic. It actively participates in the clinical processes of the Hospital on multidisciplinary case management committees for amyloidosis, multiple myeloma, primary immunodeficiencies and complex glomerulopathies.
It also works bilaterally with other departments in the clinical processes relating to autoimmunity, allergies, reproductive immunology and cancer. The department is part of the Transversal Immunology Programme on the Vall d'Hebron Campus, which facilitates collaboration with other professionals working on immunology issues in other research groups. This enables the department to have 3 different programmes of sessions covering:
The department comprises 7 immunology specialists, 2 with a more clinical profile and 5 with a laboratory profile, as well as a molecular immunology expert. There is also one supervisor and 12 technicians.1 administrator. 1 resident per year (currently 3) and an immunology pre-doc.
There are professionals linked to the immunology department who are involved in different processes:
The Cerebrospinal Fluid Laboratory is the result of a collaboration agreement with VHIR-CEMCAT (Multiple Sclerosis Centre of Catalonia), to carry out complex care tests and implement new biomarkers in multiple sclerosis in healthcare practice (translational research). This process involves a principal researcher from the Clinical Neuroimmunology research group and a technician.
The allergy unit, in conjunction with the immunology department, is actively involved in drawing up reports interpreting the results of molecular allergy testing of patients from other centres. This added value means the department is even more useful for customers.
To improve the coordination of the paediatric primary immunodeficiency process. The Immunology Department shares a biologist with the Paediatric Infectious Pathology and Immunodeficiency Unit. This biologist takes on tasks shared between the clinic and the lab.
There is collaboration with the Translational Bioinformatics Research Group to determine the pathogenicity of gene mutations in patients with primary immunodeficiency. The complementary nature of immunological, genetic, bioinformatic and functional studies of proteins allows a personalised diagnosis of patients with primary immunodeficiency, which in turn helps find treatments that are more appropriate to the molecular pathology in question.
The Immunological Regulation and Immunotherapy Research Group provides methodological and technical support to the Department of Immunology in applied research subjects. The group leader is currently co-IP on a research project (on Family Haemophagocytic Syndrome) and this collaboration will be included as part of a resident’s thesis.
Immunology, Cross-departmental services
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