IMMUNODEFICIENCY

DISEASES
GROUP MEMBERS:
Aliyan Ahmed
Sana Fasahat
Sawera Shaukat
Irma Nadeem
Prem Chand
 Wiskott-Aldrich
Syndrome
• Wiskott-Aldrich syndrome (WAS) is a rare X-linked
recessive syndrome.
• It results from a genetic mutation in the gene
encoding Wiskott-Aldrich syndrome protein
(WASp) located on the X chromosome, region p11
affecting the immune system and inducing a state of
immunodeficiency.
• It is defined by the triad of eczema,
immunodeficiency, and thrombocytopenia.
• WAS is usually lethal in childhood because of
infection, hemorrhage, or malignancy.
Laboratory Features:

• The laboratory features of WAS include a decrease in platelet number and

size with a prolonged bleeding time.

• The bone marrow contains a normal or somewhat increased number of

megakaryocytes.

• There are abnormalities in both the cellular and humoral arms of the
immune system, related to a general defect in antigen processing.

• This is manifest as a severe deficiency of the naturally occurring

antibodies to blood group antigens (isohemagglutinins)
Cont ..

• Patients with WAS can have a variety of different patterns of

immunoglobulin levels, but they usually have low levels of IgM, normal
levels of IgA and IgG, and increased levels of IgE.

• Absence of isohemagglutinins (IgM antibodies against ABO blood group

antigens) is the most consistent laboratory finding in WAS and is often
used diagnostically.

• In addition, these patients have persistently increased levels of serum

alpha-fetoprotein, which can also be a useful diagnostic feature.
• The primary molecular defect in the syndrome appears to be an
abnormality of the integral membrane protein CD43, which is involved in
the regulation of protein glycosylation.

• Abnormalities cause defective actin polymerization and affect its signal

transduction in lymphocytes and platelets.

• Platelets have a shortened half-life, and T lymphocytes are also affected,

although B lymphocytes appear to function normally.

• Splenectomy can be very valuable in controlling the thrombocytopenia.

TREATMENT:

Current treatment for this immunodeficiency is bone

marrow transplantation or cord blood stem cells from an
HLA-identical sibling
 ATAXIA –TELANGIECTASIA:

• Rare autosomal recessive syndrome .

• It is caused due to mutation in Ataxia- Telangiectasia
mutated( ATM ) gene.
• The AT gene is located on chromosome 11 , region q22.
• This abnormality results in a defective kinase involved
in DNA repair and in cell cycle control.
• Abnormal genes produce a combined defect of both
T- cell and B- cell.
 CLINCAL FEATURES:
• Characterized by cerebrellar ataxia and
telangiectasia , especially on the earlobes and
conjunctiva.

• Blood vessels in the sclera of the eyes may be dilated ,

• and there may also be a reddish butterfly
area on the face and ears.

• Increase risk of malignancy.

• Recurrent infection.
 Laboratory Findings:
• Ninety- five percent of patients exhibit increased levels of serum alpha-
fetoprotein.

• High carcinoembryonic antigen (CEA).

• Low level of IgE , IgG2 and IgA.

 TREATMENT :

The only effective therapy for AT is allogenic bone marrow transplantation.

SEVERE COMBINED IMMUNODEFICIENCY
(SCID):

• Severe combined immunodeficiency (SCID) is a group of rare,

inherited disorders that causes life-threatening problems with the
immune system.

• It is characterized by the disturbed development of functional T

cells and B cells caused by numerous genetic mutations that
result in differing clinical presentations.
TYPES OF SCID
X-Linked SCID:
• X-linked severe combined immunodeficiency (X-SCID) is the most
prevalent form of the disease in the US, accounting for about 46% of
cases.

• The IL2RG gene, located on the X chromosome, codes for the protein
called common gamma chain, which is shared by several interleukin
receptors.
JAK3 Deficiency:

JAK3 Deficiency:
• A JAK3 (Janus Kinase) deficiency may be found without the common
gamma chain deletion cause SCID affecting both males and females.

• Lymphocytes are unable to transmit signals from interleukins-2 and 4.

• Symptoms are similar to the x-linked form of the disease.

• The JAK3 gene can be found on chromosome 19, region p12.

ADA Deficiency:

ADA Deficiency:
• Adenosine deaminase (ADA) deficiency affects

15-20% of patients with SCID, causing toxic

metabolites to accumulate in lymphoid cells

and impairing proliferation of B and T cells.

• The ADA gene is located on chromosome 1,

region q21.
OTHER MOLECULAR DEFECTS IN SCID

RAG1 or RAG2 Mutations:

• These mutations cause Ommen’s syndrome, a condition in which infants
lack T and B cells causing lymphocytopenia.

• This is because the T and B cells cannot rearrange DNA to produce

functional immunoglobulins or T-cell receptors.
HLA Class II Antigen Deficiency:

HLA Class II Antigen Deficiency:

• The defective expression of HLA class II antigens found on B cells leads
to bare lymphocyte syndrome, which impairs the immune response as
these molecules are involved in antigen presentation.

CD45 Gene Mutation:

• A mutation in the gene encoding the CD45 protein has been identified.
CD45 regulates signal transduction of T- and B-cell receptors.
CLINICAL PRESENTATION OF SCID:

CLINICAL PRESENTATION OF SCID:

• Oral candidal infections, pneumonia, and diarrhea being the most common
symptoms.

• Live vaccines can also cause severe illness.

• Bone marrow transplantation or enzyme replacement is possible, SCID

patients die before reaching 2 years of age.
TREATMENT APPROACHES:

• Bone Marrow Transplantation, Enzyme Replacement Therapy for ADA

Deficiency or somatic cell gene therapy, high plasma levels of ADA
through bovine ADA conjugated with polyethylene glycol (PEG), cord
blood stem cell transplantation and red blood cell transfusion.
THANK YOU!