Clinical Diagnosis of Primary Immunodeficiencies - Hogan Flashcards
What are the most common primary immunodeficiency diseases (PID’s)?
B cell derived and antibody defects.
What are the second most common of the PID’s?
T cell disorders. They are often combined with other immunodeficiencies.
What PID’s are most rare?
Innate immune response disorders.
Describe innate immune function at birth.
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.
Is NK function available to neonates?
yes
Is T cell function available at birth?
yes
Are B cells fully functional at birth?
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.
What antibody is passed from mom to baby?
IgG antibodies cross the placenta and provide immune function for the baby until about 6 mod. of age.
Family history of autoimmune problems suggests what?
Difficulty with B cell maturation or tolerance issues at a genetic level.
If you see severe infections such as lymphadenitis, osteomyelitis, pneumonia and sepsis what system may be involved?
The innate immune system.
If you see infections with catalase producing organisms such as Staph, pseudomonas, aspergillus, candida, listeria, and Serratia what deficiency should you suspect?
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.
Failure of what leads to Neisseria infection?
Failure of the membrane attack complex in complement. Deficiency of C5-C8.
Absence of C3 of complement would result in what?
Severe bacterial infections.
Infections with what type of organism are hallmark for complement deficiencies?
Neisseria.
Chronic otitis media in adolescents suggests what?
A problem with the anatomy of the ear or an immune deficiency.
What types of infections are prominent with a B cell or humoral deficiency?
Sinopulmonary - allowed by lack of IgA.
Infections with what organism is associated with HIV?
Pneumosystis carinii.
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?
Primary immune deficiency.
What types of finding suggest T cell deficiencies?
- family history
- 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
- failure to thrive
- persistant and difficult to treat diarrhea
- no lymph nodes
- cutaneous lesions such as atopic dermatitis and severe rashes
- graft vs host disease after transfusion
- hepatosplenomegaly
What types of findings suggest B cell deficiencies?
- family history of autoimmune/immunodeficiency
- onset after 6 mos.
- recurrent virulent bacterial infections
- allergy/autoimmune disease
- vaccine failure
- sinopulmonary infections
- failure to thrive
What types of findings suggest phagocyte deficiencies?
- susceptibility to low grade bacteria and fungus
- severe infections such as pneumonia and osteomyelitis
- skin infections/furunculosis
- lymphadenitis
- abscesses
- delayed separation of the umbilical cord
If you suspect a PID and order a CBC and see neutropenia what does it suggest?
- congenital absence
- autoantibodies
- cyclic neutropenia
If you suspect a PID and order a CBC and see neutrophilia what does it suggest?
- LAD
2. infection
If you suspect a PID and order a CBC and see granule abnormality what does it suggest?
- azurophilic granules - chediak higashi disease
2. bi-lobed nucleus - specific granule deficiency
If you suspect a PID and order a CBC and see small platelets and a decreased number of platelets what does this suggest?
WAS - Wiscott alder syndrome
If you suspect a PID and order a CBC and see abnormal RBC’s what does this suggest?
autoimmune anemia and associated g6pd deficiency.
If you suspect a PID and order a CBC and see lymphopenia what does this suggest?
SCID
What is CH50 and AH50 and how do you interpret the results?
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.
If CH50 and AH50 are both zero what might be the problem?
Both cascades share C3 and C5-C9 so the problem could be here. If only one is zero then test specific complement components.
When testing Ig levels, if you see a low IgA value is this concerning?
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.
What should you test if IgG is low?
Test for albumin levels to determine if loss is secondary to kidney issues.
If a child has sinopulmonary issues what else might be the issue besides a PID?
- cystic fibrosis
2. immotile cilia syndrome
If a child has complex cardiac defects, facial defects, siezures and calcium deficiency then think what?
Digeorge syndrome.
