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:
- Kennedy Institute of Rheumatology, Oxford, (Prof. Marc Feldmann)
- Institute Pasteur, Paris (Dr. Mathew Alberts)
- Kings College, London, (Prof. Marc Peakman)
- Mount Sinai School of Medicine, New York (Dr. A Cerutti, Dr. C Cunningham-Rundles)
- Center for Chronic Immunodeficiency, Freiburg (Germany), Bodo Grimbacher
The Immunology Department laboratories have ISO 9001 certification, as do the hospital’s other clinical laboratories.
Portfolio of Services
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.
Cell Immunology Section
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).
Hypersensitivity and Allergies Section
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.
Immunotherapy Monitoring Section
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.
Rapid Response Testing
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.
Adult Clinical Immunology Outpatient Clinic
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.
Dr. Josep Sánchez de Toledo Codina, head of the Paediatric Haematology and Oncology Department, tells us about a Department that has laid the foundations for the specialism in Spain. He also remembers the evolution of transplants from haematopoietic stem cells and progenitors, from the beginning, buying the material at a shop in Barcelona city centre, to the more than 1,200 transplants that have now been performed.
Dr. Francesc Bosch, Head of the Haematology Department, talks about the complexity of the Department, which has turned Vall d’Hebron into a reference centre in haematology thanks to its commitment to transplants and the use of new treatments. The Clinical Trials Unit helps a lot, giving access to treatments for complex patients.
The Master's Degree in Biomedical and Translational Research is an official programme created to train researchers with the requisite combination of scientific knowledge and skills to contribute to the future success of biomedical research.
Fermín Fernández Álvarez, Porter Coordinator, explains the importance of the role these professionals play in the hospital. After 36 years at Vall d’Hebron, Fermín is a real master of the ways things are done. He says that a porter has to combine humility, discretion and safety with a single goal: that patients receive human and friendly treatment.