Diseases of T cell deficiency

Question 1

When do T cell defieincies present usually?

Answer 1

Usually very early in life, as infants.

Question 2

What is an expected WBC at birth?

Answer 2

Elevated WBC is normal at birth.

Question 3

What would mean a T-cell defiency unless proven otherwise?

Answer 3

Low lymphocytes for infants means a T-cell defiency unless proven otherwise.

Question 4

What would we expect for normal infant Ig levels?

Answer 4

We expect normal IgG because it is from mom, and low IgA and low IgM because they will build those over time

Question 5

What test should we use for a T-cell problem?

Answer 5

Flow cytometry will show us lymphocyte subsets

Question 6

What is CD16 found on? What about CD19?

Answer 6

CD16 is on NK cells

CD19 is on B cells

Question 7

Why does absence of a sail sign mean?

Answer 7

Lack of sail sign is absence of the thymus.

Question 8

No thymus, and infant is T-/B-/NK+ whats the dx doc?

Answer 8

This would be a SCID

Question 9

What is the treatment for SCID?

Answer 9

need a stem cell transplant

• must be placed in positive pressure isolation room
• avoid breast feeding because of CMV transmission
• start on prohpylactice Bactrim and antiviral acyclovir therapy
• pt will die within first year of life if not transplanted

Question 10

What is the most common type of SCID?

Answer 10

50% of SCID is X-linked

Question 11

What are the clinical features of SCID?

Answer 11

presents within first few months of life, recurrent episodes of diarrhea, pneumonia, otitis, sepsis and cutaneous infections

• growth is initially normal but slows and failure to thrive ensues after infection and diarrhea begin
• prone to opportunistic infections like Candida Albicans and Pneumocystis jirovecii, varicell-zoster, EBV, CMV, sick from vaccines

Question 12

What can delay dx of SCID a few months?

Answer 12

Infant looks normal because of mom IgG and initial normal growth

Question 13

What would a small thymus lack?

Answer 13

Less than 1 gram

lacks corticomedullary distinction and hassall’s corpuscles

Question 14

Does presence of thymic shadow rule out SCID?

Answer 14

No, sometimes SCID is still present in rare forms

Question 15

In normal infants what percent of lymphocytes are T cells?

Answer 15

70%

• any count under 4000 should be considered lymphopenic
• if low then must use flow cytometry

Question 16

What are the defining criteria for SCID?

Answer 16

Absolute lymphocyte less than 2500

• T cells less than 20% of total lymphocytes
• lymphocyte stimulation to mitogens is less than 10%
• absence of thymus on CXR
• Igs are low because no B cell stimulation by T cells

-

Question 17

Maternal T cells can cross the placenta and enter circulation. What is one way to tell these from the patients own?

Answer 17

Maternally engrafted cells have CD45RO (memory phenotype) and normal infant are CD45RA

Question 18

In any type of SCID what are the options for T cell levels, B cell levels, and NK levels?

Answer 18

In any type of SCID T cell levels are always diminshed or absent, but B cell and NK cell numbers can be variable

Question 19

What is the phenotype of X-linked SCID? What is it caused by?

Answer 19

X- linked SCID is T-B+NK-

Defect on X chromosome encoding the cytokine receptor subunity common gamma chain, IL2 receptor gene.

-gamma C is also involved in growth hormone receptor signlaing adding to failure to thrive in addition to recurrent infections and nutritional deficiencies

Question 20

How do you differentiate X-linked SCID with IL-2gamma chain receptor mutation vs. Autosomal Recessive SCID with a JAK-3 SCID?

Answer 20

Use a functional STAT5 tyrosine phosphorylation assay.

-presence of tyrosine-phosphorylated STAT5 by flow cytometry after IL02 stimulation idicates a functional IL-2/JAK-3 signal transduction pathway

Question 21

ADA deficiency leads to what SCID phenotype and what are some characterizing symptoms for diagnosis?

Answer 21

T-B-NK-

Accumulation of adenosine, 2-deoxyadenosine and 2-o-methyladenosine.

• accumulation is toxic and leads to thymocyte death
• presents similar to other SCIDs with recurrent infections, failure to thrive and recurrent diarrhea. However can also present with skeletal abnormalities and

Question 22

JAK3 de

Question 23

What is treatment for ADA deficiency?

Answer 23

Cured with HLA-indentical or haploidentifcal T cell depleted bone marrow transplant.

-or enzyme replacement with PEG-ADA however, immunocompetance is not near the level of those who have undergone bone marrow transplantation

Question 24

JAK3 defiency leads to what SCID phenotype? and what is the cause of it?

Answer 24

T-B+NK-

this is a downstream cytokine signaling usse, not a problem with TCR activation.

-presents with abnormal B cell function despite high number of B cells often.

Question 25

IL-7 receptor alpha is specifically only for what type of cell development?

Answer 25

T-cell development (hence the patients have functional B cells and NK cells)

Question 26

RAG-1/2 SCID leads to what SCID phenotype?

Answer 26

T-B-NK+

-RAG1/2 is required for VDJ recombination so therefore it effects T cells and B cells but not NK cells

Question 27

What is best neborn screening to find T and disorders?

Answer 27

TRECS (T cell excision circles)

• measures T cells emigrating from the thymus (mature)
• low to absent in neonates who make no of few T cells
• slightly lower in premature infants

Newborn screening is called a Guthrie Card

Question 29

A 3 day old infant with hypoxia, heart defect, low calcium and tetany of the face.

He is tachycardic, tachypnea, Sp)2 is 85%

-presents with low set eary, cleft palate, skin is pink without rash, murmor

T cells are low but NK and B cells are normal. Whats the dx doc?

Answer 29

This is DiGeorge Syndrome a T-B+NK+ SCID

-due to a 22q11.2 deletion leading to a failure of development in the 3rd and 4th pharyngeal pouch system

Question 30

What is CATCH 22?

Answer 30

Clinical presentation for DiGeorge

C = Cardiac Anomalies

A = Abnormal Facies

T = Thymus aplasia (hypoplasia in partial Digeorge)

C = cleft palate

H = hypocalcemia/hypoparathyroidism

22 = 22q11.2 deletion