Done by : FATIMAH ALLUWAIMGroup NO. : 3Tutor : DR. DALIA ASHOR

Selective IgA deficiency

Objectives• class switching.• affinity maturation.• What is immunoglobulin.• IgA Definition.• IgA types.• Definition of Selective IgA deficiency .• Types.• Causes.• Risk factors.• Pathophysiology.• Symptoms.• Diagnosis.• Treatment.• What is the adverse reaction.• The patient can take influenza vaccination and other vaccines.

Immunoglobulin

Antibodies are substances made by the body's immune system in response to bacteria, viruses, fungus or cancer cells. Antibodies attach to the foreign substances so the immune system can destroy them.

class switching

Isotype class switching is a biological mechanism that changes a B cell's production of antibody from one class to another. for example, from an isotype called IgM to an isotype called IgA.

What is the affinity maturation

It is the process by witch the affinity of antibodies produced in response to protein antigen increases with prolonged or repeated exposure to that antigen.

Where do you think Affinity maturation occurs ?

• Affinity maturation occurs in the germinal centers of lymphoid follicles.

• Two interrelated processes, occurring in the germinal centers of the secondary lymphoid organs:

1. somatic hypermutation.2. clonal selection.

Molecular basis of affinity maturation

1. Activation of B cells and migration into germinal center.

2. B cell proliferation.3. Somatic hypermutation of Ig genes.4. B cell recognition of antigen on follicular dendritic

cells, selection of high-affinity B cells.5. Death of B cells that do not bind antigen. 6. Generation of memory and balsama cells.

Immunoglobulin A• Immunoglobulin A (IgA), as the major class of

antibody present in the mucosal secretions.• represents a key first line of defense against

invasion by inhaled and ingested pathogens at the vulnerable mucosal surfaces.

IgA Subclasses

• IgA1, comprises approximately 85% of total IgA concentration in serum. IgA1 shows a good immune response to protein antigens and, to a lesser degree, to polysaccharide and lipopolysaccharides.

• IgA2, representing only up to 15% of total IgA in serum, plays an important role in the mucosa of the airways, eyes, and the gastrointestinal tract to fight against polysaccharide and lipopolysaccaride antigens. It also fighting bacterial infections.

Secreting form

Selective IgA deficiency

Selective deficiency of IgA is the most common (PIDD). Persons with this disorder have low or absent levels of a blood protein called IgA.

Do you know why the disorder termed “selective”

Classification

• Severe IgA deficiency refers to serum levels below 0.7 mg/mL, which is the lower limit of detection for most assays.

• Partial IgA deficiency refers to serum levels above 0.7 mg/mL, but below the lower limit of normal.

causes• Unknown in many cases.• mutation of heavy chain constant regionin

some.• IgA deficiency is could be inherited (20% of

cases) , which means it is passed down through families. It may be inherited as an autosomal dominant or autosomal recessive trait.

PATHOPHYSIOLOGY

“B lymphocytes are unable to produce Ig A”

Risk factor

• Caucasians People have a higher risk factor, it is found in approximately 1 in 700 individual.

• Family history especially if the patient has First-degree relative in this condition.

Symptoms (1)85–90% of IgA-deficient individuals are asymptomatic.

The most common symptom of Selective IgA Deficiency is susceptibility to infections including:

• Bronchitis.• Chronic diarrhea.• Conjunctivitis.• Gastrointestinal inflammation.• Mouth infection.

Symptoms (2)• Otitis media.• Pneumonia.• Sinusitis.• Skin infections.• Upper respiratory tract infections.• Bronchietasis(a disease in which the small air sacs in the lungs

become damaged and enlarge).• Unexplained asthma.

Diagnosis

Patient & family history.

Quantitative immunoglobulins.

Serum Immunoelectrophoresis.

Patient & family history

• Family history of selective IgA deficiency.• Either chronic or recurrent infections,

allergies, auto-immune diseases, chronic diarrhea, or some combination of these problems.

Quantitative immunoglobulins

• rapid and accurate measurement of the amounts of the immunoglobulins M, G, and A.

• tests of blood serum demonstrate absence of IgA with normal levels of the other major classes of immunoglobulins (IgG and IgM).

NORMAL results of Ig M, G and A

IgG 560 to 1800 mg/dL

IgM 45 to 250 mg/dL

IgA 100 to 400 mg/dL

Serum Immunoelectrophoresis

• detect the presence of certain antibody.• It is used to detect if the patient have

anti-IgA antibodies.

Complication

• An autoimmune disorder such as rheumatoid arthritis.

• severe, even life-threatening, reactions to transfusions of blood and blood products because they develop anti-IgA antibody .What if transfusions are necessary?

• Some patients develop common variable immunodeficiency.

Management

• patients who do not have any symptoms do not need any treatment.

• prevent anaphylactic reaction secondary to blood transfusion.

• treatment of associated diseases.

Treatment

• No specific treatment is available. Some people gradually develop normal levels of IgA without treatment.

• Infections should be treated with antibiotics.

• Those with selective IgA deficiency who also have IgG subclass deficiencies can benefit from Intravenous immunoglobulin (IVIG).

Intravenous immunoglobulin (IVIG)

• It is a sterile solution of concentrated antibodies extracted from healthy donors which is administered into a vein.

• IVIG is used to treat disorders of the immune system or to boost immune response to serious illness.

The side effects for IVIG treatment (1)

• People with complete IgA deficiency may develop anti-IgA antibodies if given blood products and IVIG. This may lead to allergies or life-threatening anaphylactic shock.

(These individuals can safely be given IgA-depleted IVIG if this deficiency is also associated with IgG subtype deficiency)

The side effects for IVIG treatment (2)

• Headache.• dermatitis - usually peeling of the skin.• infection (such as HIV or viral hepatitis). • damage such as hepatitis caused directly by

antibodies contained in the pooled IVIG.• acute kidney injury.• venous thrombosis.

Prevention

There is no means of prevention of Selective IgA Deficiency.• Because IgA Deficiency does not become detectable

until approximately six months of age, prenatal and neonatal detection of this disorder is currently not possible.

• But genetic counseling may be of value to prospective parents with a family history of selective IgA deficiency.

• Vaccines, including the pneumococcal vaccine, may be administered to prevent infections that are commonly associated with the disorder.

Vaccination and IgA deficiency

• Local live virus vaccine, such as intranasal influenza vaccine, yellow fever vaccine and live rotavirus vaccine, should not be given to patients with IgA deficiency until their immune status is fully evaluated.

• Other vaccines, such as those against pneumococcus, are specifically recommended.

References

• Basic Immunology, Abbas 3th ed.• http://www.nlm.nih.gov/medlineplus/ency/a

rticle/001476.htm• http://www.ncbi.nlm.nih.gov/pmc/articles/P

MC2821513/• http://primaryimmune.org/wp-content/uplo

ads/2011/04/Selective-IgA-Deficiency.pdf• http://www.cdc.gov/vaccines/pubs/pinkbook

/downloads/appendices/A/immuno-table.pdf• http://bandbacktogether.com/Immunoglobul

in-A-IgA-Deficiency-resources/• http://www.healthcentral.com/ency/408/001

476.html?ic=506019• http://www.aaaai.org/conditions-and-treatm

ents/primary-immunodeficiency-disease/selective-iga-deficiency.aspx