Immunology and Immunotherapy

The Clínica Universidad de Navarra is a pioneer in the development of Immunotherapy strategies for the treatment of cancer and in recent years it has also been working on strategies for the treatment of autoimmune diseases.

A comprehensive and transversal programme is being developed which combines basic and translational research with the clinical application of new therapeutic approaches.

To undertake the basic and preclinical activity, we work in close collaboration with the Immunology and Immunotherapy and Hemato-Oncology Programmes of the Cima Universidad de Navarra.

The main objectives of this multidisciplinary programme are:

• Development of therapeutic vaccines against different types of cancer and other pathologies such as autoimmune and infectious diseases.
• Adoptive cell therapy strategies for the treatment of different pathologies (cancer and infectious diseases).
• Combined immunotherapy strategies.

A fundamental aspect is the transfer of the results of preclinical research to the clinic.

For this purpose, the Clínica Universidad de Navarra relies on the Cellular Therapy Area, which has the technology and facilities necessary for the manufacture of all immunotherapy products related to cell therapy. In particular, it has the GMP laboratory that, certified by the AEMPS, complies with the principles and guidelines of Good Manufacturing Practice laid down in Directive 2003/94/EC.

One of the clinical activities of the Clinic's Immunology Service is the study and detection of autoantibodies, which contributes to the diagnosis of different autoimmune diseases.

The goal is to detect and characterise autoantibodies related to various pathologies:

• Systemic autoimmune diseases that affect different organs (skin, joints, kidney, muscle, blood vessels...).
• Autoimmune liver diseases (hepatitis, primary biliary cirrhosis...)
• Inflammatory pathology of the blood vessels (vasculitis...)
• Celiac disease.
• Inflammatory bowel disease (Crohn's disease, ulcerative colitis).
• Autoimmune diseases with alterations in coagulation.
• Autoimmune endocrine diseases (diabetes, thyroiditis, Addison's disease...).
• Autoimmune diseases of the central and peripheral nervous system (myasthenia gravis, polyneuropathies...)
• Autoimmune gastritis.
• Blistering skin diseases.
• Autoimmune platelet diseases.

Techniques:

• Indirect immunofluorescence.
• Chemiluminescence.
• ELISA.
• Immunoblot.

We control the quality of our techniques by participating in all UK-NEQAS Autoimmunity programmes on a monthly basis.

The Flow Cytometry Unit of the Immunology Service of the Clínica Universidad de Navarra carries out its work at CIMA LAB Diagnostics, in close collaboration with the Cytogenetics and Molecular Biology Units, and has advanced equipment, including up-to-date cytometers and cell separators. 

Our activity is mainly focused on:

• Diagnosis of haematological neoplasms such as leukaemias, lymphomas and multiple myeloma.
• Study of minimal residual disease.
• Diagnosis of tumour infiltration in cerebrospinal fluid.
• Differential diagnosis of monoclonal banding.
• Diagnosis of paroxysmal nocturnal haemoglobinuria.
• Diagnosis of coeliac disease by duodenal cytometry (analysis of intraepithelial lymphocytes).
• Quantification of CD34+ cells for bone marrow transplantation.
• CD4/CD8 ratio in HIV+ patients.
• Study of the distribution of lymphocyte subpopulations.
• Quantification of regulatory T-lymphocytes.
• Others.

We control the quality of our techniques through continuous participation in external quality controls organized by UK-NEQAS, Iberian Society of Cytometry and Spanish Society of Immunology.

The Immunology Service has been accredited as the Reference Histocompatibility Laboratory of Navarra since 1979, and by the European Federation of Immunogenetics since 2013.

It carries out studies on the typification of HLA molecules involved in the phenomenon of allograft rejection, and associated with certain diseases, as well as the study and monitoring of anti-HLA antibodies in patients on the transplant waiting list.

Typing of HLA class I molecules (HLA-A, HLA-B and HLA-C) and II molecules (HLA-DRB1, HLADQA1 and HLA-DQB1), using PCR-SSO and PCR-SSP techniques.

Donor-recipient compatibility study in solid organ (kidney, heart and liver) and bone marrow transplants.

HLA association with various diseases: ankylosing spondylitis, celiac disease, retinopathy in pellets, narcolepsy, Behçet's disease, hypersensitivity reaction to abacavir...

Detection and analysis of specificities of anti-HLA class I and class II antibodies, mainly to patients on waiting lists for renal, cardiac and hepatic transplants, but also in the context of transfusion reactions, using techniques:

• Cytotoxicity technique.
• Luminex technique.Cross-match test for solid organ transplants, using techniques:
  • Cytotoxicity technique.
  • Cytometry technique.

We control the quality of our techniques by participating in the quality control organised by GECLID-Spanish Society of Immunology, which takes place every six months.

T-lymphocytes, NK cells and cells of the mononuclear phagocytic system are components of the immune system responsible for the elimination of a large number of pathogenic elements. Their degree of activation and proliferation determines the immune response to these infectious antigens.

Evaluation of the functional immune response

There are various determinations that allow the evaluation of the patient's functional immune response:

• Study of T lymphocyte subpopulations by flow cytometry.
• Study of B lymphocyte subpopulations by flow cytometry.
• Analysis of the expression of molecules relevant to the immune response (CD40L...)
• Oxidative activity of monocytes and granulocytes Phagocytosis mediated by polymorphonuclear neutrophils and monocytes is one of the body's main defences against infection.
• Response to mitogens by CFSE technique.
• Immunological test that evaluates the capacity of lymphocyte cells to proliferate against mitogens.
• It is an essential tool for the diagnosis of cell-based immunodeficiencies.
• NK activity. NK (natural killer) cells are essential for the body's defence against viruses and tumour cells.
• Study of cytokines produced by lymphocytes and monocytes Cytokines are soluble proteins that play a fundamental role in regulating the immune response.