In the past few years, mutations in several different genes have been found to be associated with CVID. These include inducible co-stimulatory (ICOS) in one family and a protein on B-cells (CD19) in several families as causes of autosomal recessive CVID. Mutations in a cell receptor (TACI) for two factors (BAFF or APRIL) needed for normal growth and regulation of B-cells have also been found in about 10% of patients with CVID. A causative role of these mutations in the immune defect is not yet clear since some of these mutations can be found in people with normal immunoglobulins
Common variable immunodeficiency
Common VariableImmunodeficiency Fatima Al-Awadh
Objectives• Describe the immune system.• Mention the ways of activating B lymphocytes.• Recognize the types of antibodies.• Describe the Isotype switching.• Define Immunodeficiency.• Define the common variable immunodeficiency.• Mention causes, pathophysiology, Signs & Symptoms, Complications, Diagnosis, Differential diagnosis, Management and Prevention.
The immune system• Immunity is defined as resistance to disease, specifically infectious disease.• The collection of cells, tissues, and molecules that mediate resistance to infections is called the immune system, and the coordinated reaction of these cells and molecules to infectious microbes is the immune response.• Immunology is the study of the immune system and its responses to invading pathogens.• The physiologic function of the immune system is to prevent infections and to eradicate established infections.
ImmunodeficiencyDefects in the development and functions of the immune system result in Increased susceptibility to infections reactivation of latent infections increased incidence of certain cancers
Immunodeficiency• Disorders caused by defective immunity are called immunodeficiency diseases.• Some may result from genetic abnormalities in one or more components of the immune system; these are called congenital (or primary) immunodeficiencies.• Other defects may result from infections, nutritional abnormalities, or medical treatments; these are called acquired (or secondary) immunodeficiencies.
The Common variable Immunodeficiency• Common variable immunodeficiency is a heterogeneous group of disorders that represent a common form of primary immunodeficiency.• These disorders are characterized by poor antibody responses to infections and reduced serum levels of IgG, IgA, and often IgM.
Genetic Causes• Due to the unclear genetic nature of CVID, a clear pattern of inheritance has not been defined.• In some instances, more than one family members are deficient in one or more types of immunoglobulins• CVID is autosomal recessive. Gene Mutations in CVID inducible co- Mutations in a protein on B- stimulatory cell receptor cells (CD19) (ICOS) (TACI)
Causes• The underlying causes of common variable disease are poorly understood but include defects in B call maturation and activation.• Some patients have mutations in genes encoding receptors for B cell growth factors or co-stimulators involved in T cell-B cell interactions.
Pathophysiology Changes in thehumoral response mediated response Changes in the cell- • Failed B cell • T cell differentiation abnormalities with impaired present as well, secretion of therefore, this is a immunoglobulins global immune dysfunction disease
Signs & Symptoms• frequent and chronic bacterial, viral or fungal infections (bronchitis, pneumonia, ear or skin infections etc.)• chronic sinusitis or upper respiratory damage, bronchiectasis• fatigue• lymph gland enlargement• joint pain or arthritis (may be due to infection)• hair loss• infections or disorders of the digestive tract, diarrhea• anemia• spleen enlargement
Complicationslymphoma autoimmune premature disease death
Diagnosis• Testing is done by measuring immune globulin levels in the blood. Supportive tests such as antibody response tests and CT scan of sinus or lungs may also be utilized.• CVID often goes undiagnosed until symptoms are more profound, in the second to fourth decade of life.
Differential DiagnosisPrimary hypogammaglobulinemia: • X-linked agammaglobulinemia • SCID: atypical infections, T cell defects, or dysmorphic features • Hyper-IgM syndrome: neutropenia, with normal or elevated IgM and absent IgGSecondary hypogammaglobulinemia: • Decreased production o Malignancy: thymoma, CLL, lymphoma o Drugs: immunosuppresants, antiepileptics o Viral infections: EBV, HIV, CMV, parvovirus B19 o Systemic illnesses causing bone marrow suppression • Increased loss o Protein-losing enteropathies o Nephrotic syndrome o Burn victims
Management • IVIG is the mainstay of treatment. • Treatment of infections. • Surveillance for autoimmunity & malignancy.
Prevention• Inheritance patterns vary among patients and are not present in most patients, making this disorder impossible to prevent.