T lymphocyte deficiencies

Question 1

ADA deficiency

Answer 1

 .8-15% of SCID patients  .Accumulation of dATP inhibits DNA replication & repair and
leads to T and B lymphocyte apoptosis  profound
lymphopenia.  Treatment
a. Bone marrow transplant b. Gene transfer (2002) c. Poly ethylene glycol conjugated Adenosine Deaminase (PEG-ADA) injections.
 Patients with milder phenotypes may present at older ages.

Question 2

Purine Nucleoside Phosphorylase deficiency

Answer 2

 Milder immune deficiency than adenosine deaminase  Slight accumulation of dGTP & decreased GTP  Cerebral palsy like neurol. Abnormalities.  Treatment: BMT

Question 3

x-linked SCID

Answer 3

 46% of SCID patients  Common gamma chain (γc) deficiency. Together with IL-2R
and IL-2Rβ form IL-2 receptor, major role in signal transduction
via Jak3 tyrosine kinase (30% rate of new mutations per
generation)  IL-2, IL-4, IL-7, IL-9, IL-15, IL-21 receptors affected.
 a.Major role of IL-7 in inducing survival of early T cell
progenitors in thymus.  b.Major role of IL-15 (and SCF stem cell factor) in generating
NK cells from CD34+ marrow progenitors.
 Severe T lymphopenia (T-B+NK-), present in 1st months of life
with thrush, diarrhea or pneumonia.  More than half are engrafted with maternal lymphocytes
 Graft versus host disease
a. General concepts of GVHD b. Prevention
 . Treatment
a. Bone marrow transplant
b. Gene transfer Complication: Acute leukemia
 Carrier mothers have only normal X chromosome expressed in
lymphocytes (lymphocytes with abnormal X chromosome fail to
reach maturation)
B. IL-7 receptor  C. IL-2 receptor  (CD25) deficiency (only one patient reported)
 Absence of T cell proliferation despite IL-2 production.

Question 4

Deficiency of T cell receptor chains (, δ,  & ζ)

Answer 4

Zeta chain deficiency described May 2006 NEJM. Recurrent
infections,T lymphopenia, elevated immunoglobulins but no specific antibodies. Successfully treated w BMT at 30 months of age.

Question 5

Deficiency of production of IL-2

Answer 5

Bone marrow transplant ineffective Treat with IL-2 injections

Question 6

MHC class 1 deficiency

Answer 6

Class I (Transporter gene abnormalities)
TAP-1 & TAP-2 (Transporters associated with Antigen Processing)

Question 7

MHC class II deficiency

Answer 7

a. RFX mutationb. CIITA (Class II Transactivator) mutations c. North African

Question 8

Digeorge syndrome

Answer 8

Cardiac, Parathyroid, Immune deficiency

Question 9

Wiskott Aldrich syndrome

Answer 9

 Eczema, thrombocytopenia, progressive immune deficiency  X linked recessive (one case seen in a girl Autosomal inheritance)  WASP (Wiskott Aldrich Syndrome Protein) gene identified 1994. It is
an important transcription factor of lymphocyte & platelet function.
CD43 expression on lymphocytes is low.  Treat: Bone marrow & correction of immune deficiency, eczema &
thrombocytopenia  10% of patients die of lymphoreticular malignancy as adolescents or
young adults.

Question 10

ataxia telgniectsia

Answer 10

 Ataxia  Telangiectasias  Progressive decline in immune function  Strong predisposition to develop malignancy

Question 11

x-linked lymphoproliferative syndrome

Answer 11

 EBV infections fatal lymphoproliferation, aplastic anemia, or hypogammaglobulinemia
 Defective SAP (SLAM Associated Protein)  Bone marrow transplant

Question 12

autoimmmune lymphoproliferative syndrome (ALPS)

Answer 12

Fas abnormality. Abnormal apoptosis