Immunology

Last updated 07/19/2017 - Written by Melissa Stone MD

Warning Signs of Primary Immunodeficiency
1.      Family history of immunodeficiency or unexplained early death
2.      Need intravenous antibiotics to clear infections
3.      Two or more months of antibiotics with little effect
4.      Six or more new infections within one year
5.      Two or more serious sinus infections or pneumonias within one year
6.      Four or more new ear infections within one year
7.      Two or more episodes of sepsis or meningitis in a lifetime
8.      Recurrent or resistant candidiasis
9.      Recurrent tissue or organ abscesses
10.  Infection with an opportunistic organism
11.  Complications from a live vaccine
12.  Chronic diarrhea or failure to thrive
13.  Wounds that don’t heal or extensive skin lesions
14.  Unexplained autoimmunity, fevers, granulomas, or persistent lymphopenia

Common Mimickers of Primary Immunodeficiency
1.      Normal children with multiple upper respiratory illnesses
2.      Normal children with chronic allergic rhinitis mistaken for recurrent upper respiratory illness or bacterial sinusitis
3.      Children with chronic illnesses that put them at risk for recurrent infections

Critical Elements of the Medical History for Evaluating Immunodeficiency
1.      Age at onset
a.       4-5 months: combined T immunodeficiency, innate defense immunodeficiency
b.      7-9 months: B cell immunodeficiency
2.      History of recurrent infections
a.       Sites of infection
b.      Types of infection
c.       Response to treatment
3.      Gastrointestinal symptoms
4.      Autoimmune disease
5.      Family history
6.      Adverse reactions to vaccines

Preliminary work-up for primary immunodeficiency can include
-          CBC
-          Lymphocyte Subsets (T+ B+ NK)
-          Mitogen & Antigen induced Lymphocyte PNL
-          Immunoglobulin Panel, Quantitative (IgA, IgG, IgM)
-          Vaccination titers
-          CH50

Lymphocyte Proliferation Panel for Mitogens and Antigens Interpretation
-          Mitogens: PHA, Con A, PWM
o   Expect normal mitogens in infancy and childhood
o   PHA and Con A act on T cells while PWM acts on B cells
-          Antigens: Candida, Tetanus, Tuberculin
o   Normal to have low antigens in infancy due to limited exposure
o   Very high antigens in infancy is suspicious for Candida, Tetanus, or Tuberculosis infection, respectively based on elevated level
o   All children should have normal antigen responses otherwise immunodeficiency should be suspected unless:

§  Children with waning tetanus immunity may have low Tetanus
§  Children who have never had a PPD may have low Tuberculin

Vaccine Titer Interpretation
-          Pneumococcal titers
o   Send IgG antibody titers
o   Order 14 titers if young and has completed PCV13 series, order 23 titers if older and has received

PCV23
o   Titers above 0.3 mcg/mL are considered protective
o   50% protective titers expected for 2-5 yo; 70% for >5 yo; 0% if unvaccinated
o   If poor responses, often repeated after vaccination to see response
-          Measles, mumps, rubella
o   Can send specific IgG after receive 12 mo MMR vaccine
o   Considered protective if IgG is present
-          Diphtheria and tetanus
o   Can send antitoxoids after receive primary vaccine series
o   Considered protective if antitoxoids present

CH50 Deficiency Interpretation
-          CH50 is best screening test for complement deficiency
-          If value is 0, suggests a deficiency in one of the components: C1-C8
-          If value is 50% normal value, suggests a deficiency in C9
-          Specialized work-up would include AH50 to screen for deficiency in factor B, factor D, or properdin

Innate Defense Immunodeficiency
-          Screening testing:
o   Absolute granulocyte count
o   CH50
o   DHR Flow Cytometric Assay (Mayo Clinic)
o   Flow cytometry for leukocyte adhesion molecules
-          Advanced testing:
o   AH50, complement components
o   Phagocytic assays
o   Chemotaxis assays
o   Analysis of toll-like receptor pathways
o   Soluble IL-2R (Cincinnati Children’s)
o   Molecular analysis for specific defects

T Cell Immunodeficiency
-          Screening testing:
o   Checking New York State Newborn Screen for SCID
o   CXR and/or neck ultrasound to evaluate thymus development in an infant
o   Absolute lymphocyte count
o   Delayed skin hypersensitivity to recall antigens
o   Lymphocyte subsets
-          Advanced testing:
o   Mitogen & Antigen induced Lymphocyte PNL
o   NK and ADCC activity
o   Production of cytokines
o   Functional response to cytokines
o   Signal transduction studies
o   Molecular analysis for specific defects

B Cell Immunodeficiency
-          Screening testing:
o   Quantitative serum immunoglobulins
o   Specific antibodies to vaccine responses
o   Isohemagglutinins
o   B cell quantitation by flow cytometry
-          Advanced testing:
o   In vitro B cell immunoglobulin production
o   Regulation of immunoglobulin synthesis
o   CD40 ligand-CD40 interactions
o   B-cell subsets
o   Molecular analysis for gene deletions or mutations

Resources for Families

-          Primaryimmune.org

Send Out Labs

• Cincinnati Children’s Send Out Lab Form
• All labs can be ordered through Epic unless otherwise noted