Clinical Diagnosis of Primary Immunodeficiencies - Hogan

Question 1

What are the most common primary immunodeficiency diseases (PID’s)?

Answer 1

B cell derived and antibody defects.

Question 2

What are the second most common of the PID’s?

Answer 2

T cell disorders. They are often combined with other immunodeficiencies.

Question 3

What PID’s are most rare?

Answer 3

Innate immune response disorders.

Question 4

Describe innate immune function at birth.

Answer 4

Leukocyte development has passed from the liver to the spleen to the bone marrow before birth and phagocyte functionality is complete in neonates. Some complement function is available via maternally derived IgG but antibody mediated complement fixation will lag until antibody production is initiated.

Question 5

Is NK function available to neonates?

Answer 5

yes

Question 6

Is T cell function available at birth?

Answer 6

yes

Question 7

Are B cells fully functional at birth?

Answer 7

No, B cell function will not be like adults until about 2 years of age. If there is a T cell problem at birth then there will be a B cell problem also.

Question 8

What antibody is passed from mom to baby?

Answer 8

IgG antibodies cross the placenta and provide immune function for the baby until about 6 mod. of age.

Question 9

Family history of autoimmune problems suggests what?

Answer 9

Difficulty with B cell maturation or tolerance issues at a genetic level.

Question 10

If you see severe infections such as lymphadenitis, osteomyelitis, pneumonia and sepsis what system may be involved?

Answer 10

The innate immune system.

Question 11

If you see infections with catalase producing organisms such as Staph, pseudomonas, aspergillus, candida, listeria, and Serratia what deficiency should you suspect?

Answer 11

Think neutrophil disorder such as CGD. In particular Serratia is a bacteria that should easily be handled by the immune system so if you see an infection with this organism be suspicious of a PID.

Question 12

Failure of what leads to Neisseria infection?

Answer 12

Failure of the membrane attack complex in complement. Deficiency of C5-C8.

Question 13

Absence of C3 of complement would result in what?

Answer 13

Severe bacterial infections.

Question 14

Infections with what type of organism are hallmark for complement deficiencies?

Answer 14

Neisseria.

Question 15

Chronic otitis media in adolescents suggests what?

Answer 15

A problem with the anatomy of the ear or an immune deficiency.

Question 16

What types of infections are prominent with a B cell or humoral deficiency?

Answer 16

Sinopulmonary - allowed by lack of IgA.

Question 17

Infections with what organism is associated with HIV?

Answer 17

Pneumosystis carinii.

Question 18

If you see certain infections in places that are abnormal such candida in the lungs and esophagus, systemic mycobacterial infection and systemic viral illness then think what?

Answer 18

Primary immune deficiency.

Question 19

What types of finding suggest T cell deficiencies?

Answer 19

1. family history
2. if lots of infections associated with lack of T cells like severe fungal and viral infection and opportunistic infections before 6 mos. - baby should have T cells at birth
3. failure to thrive
4. persistant and difficult to treat diarrhea
5. no lymph nodes
6. cutaneous lesions such as atopic dermatitis and severe rashes
7. graft vs host disease after transfusion
8. hepatosplenomegaly

Question 20

What types of findings suggest B cell deficiencies?

Answer 20

1. family history of autoimmune/immunodeficiency
2. onset after 6 mos.
3. recurrent virulent bacterial infections
4. allergy/autoimmune disease
5. vaccine failure
6. sinopulmonary infections
7. failure to thrive

Question 21

What types of findings suggest phagocyte deficiencies?

Answer 21

1. susceptibility to low grade bacteria and fungus
2. severe infections such as pneumonia and osteomyelitis
3. skin infections/furunculosis
4. lymphadenitis
5. abscesses
6. delayed separation of the umbilical cord

Question 22

If you suspect a PID and order a CBC and see neutropenia what does it suggest?

Answer 22

1. congenital absence
2. autoantibodies
3. cyclic neutropenia

Question 23

If you suspect a PID and order a CBC and see neutrophilia what does it suggest?

Answer 23

1. LAD

2. infection

Question 24

If you suspect a PID and order a CBC and see granule abnormality what does it suggest?

Answer 24

1. azurophilic granules - chediak higashi disease

2. bi-lobed nucleus - specific granule deficiency

Question 25

If you suspect a PID and order a CBC and see small platelets and a decreased number of platelets what does this suggest?

Answer 25

WAS - Wiscott alder syndrome

Question 26

If you suspect a PID and order a CBC and see abnormal RBC’s what does this suggest?

Answer 26

autoimmune anemia and associated g6pd deficiency.

Question 27

If you suspect a PID and order a CBC and see lymphopenia what does this suggest?

Answer 27

SCID

Question 28

What is CH50 and AH50 and how do you interpret the results?

Answer 28

These are assays of the complement system for the classical pathway and the alternate pathway. If there is a genetic deficiency somewhere in the cascade the value will be 0. caveat - if there has been sepsis you will also see a zero value because complement is depleted. You can do specific labs is screening is abnormal.

Question 29

If CH50 and AH50 are both zero what might be the problem?

Answer 29

Both cascades share C3 and C5-C9 so the problem could be here. If only one is zero then test specific complement components.

Question 30

When testing Ig levels, if you see a low IgA value is this concerning?

Answer 30

IgA is primarily in the mucosa and not serum so any value greater than the bottom of measurable assay is good. Remember - infant levels are different than adult levels.

Question 31

What should you test if IgG is low?

Answer 31

Test for albumin levels to determine if loss is secondary to kidney issues.

Question 32

If a child has sinopulmonary issues what else might be the issue besides a PID?

Answer 32

1. cystic fibrosis

2. immotile cilia syndrome

Question 33

If a child has complex cardiac defects, facial defects, siezures and calcium deficiency then think what?

Answer 33

Digeorge syndrome.