Common Variable Immunodeficienc

yFatima 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.

The components of the immune system

Ways to Activate B Lymphocytes

Complement activationHelper T lymphocyte activation

1. Complement Activation

2. Helper T Lymphocyte Activation

Antibodies

StructureTypes

Isotype Switching

Structure of Antibody

Types of Antibodies

Isotype Switching

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-stimulatory

(ICOS)

protein on B-cells (CD19)

Mutations in a cell

receptor (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.

PathophysiologyC

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se • Failed B cell differentiation with impaired secretion of immunoglobulins

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se• T cell abnormalities present as well, therefore, this is a 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

Complications

lymphoma autoimmune disease

premature 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 IgG

Secondary hypogammaglobulinemia:• Decreased production

o Malignancy: thymoma, CLL, lymphomao Drugs: immunosuppresants, antiepilepticso Viral infections: EBV, HIV, CMV, parvovirus B19o Systemic illnesses causing bone marrow suppression

• Increased losso Protein-losing enteropathieso Nephrotic syndromeo 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.

References• Basic Immunology, Abbas 3th ed.• http://

www.immunedisease.com/pdf/common-variable-immunodeficiency-cvid.pdf

• http://medicine.ucsf.edu/education/resed/Chiefs_cover_sheets/CVID.pdf

• http://www.info4pi.org/aboutPI/index.cfm?section=aboutPI&content=syndromes&area=4&CFID=2813523&CFTOKEN=3

• http://voices.yahoo.com/common-variable-immune-deficiency-cvid-symptoms-diagnosis-424431.html