Primary Immunodeficiency is a group of over 550 genetic disorders of the immune system that are chronic, serious, and sometimes life-threatening. At the Jeffrey Modell Foundation we are spreading awareness of Primary Immunodeficiency to accelerate earliest possible diagnosis. 

Today’s blog post explores journey to diagnosis for people with Primary Immunodeficiency including the Warning Signs and diagnostic methods.

What are signs that I might have Primary Immunodeficiency?

The symptoms of Primary Immunodeficiency may vary by person and genetic defect, but the Jeffrey Modell Foundation has developed the 10 Warning Signs of Primary Immunodeficiency to help you understand the signs of a potential Primary Immunodeficiency for you or someone you know.

For children, the 10 Warning Signs of Primary Immunodeficiency are:

  • Four or more new ear infections within one year
  • Two or more serious sinus infections within one year
  • Two or more months on antibiotics with little effect
  • Two or more pneumonias withing one year
  • Failure of an infant to gain weight or grow normally
  • Recurrent, deep skin or organ abscesses 
  • Persistent thrush in mouth or fungal infection on skin
  • Need for intravenous antibiotics to clear infections
  • Two or more deep-seated infections including septicemia
  • A family history of Primary Immunodeficiency 

For adults, the 10 Warning Signs of Primary Immunodeficiency are:

  • Two or more new ear infections within one year
  • Two or more new sinus infections within one year (in the absence of allergy)
  • One pneumonia per year for more than one year
  • Chronic diarrhea with weight loss
  • Recurrent viral infections (cold, herpes, warts, condyloma)
  • Recurrent need for intravenous antibiotics to clear infections
  • Recurrent, deep abscesses of the skin or internal organs
  • Persistent thrush or fungal infection on skin or elsewhere
  • Infection with normally harmless tuberculosis-like bacteria
  • A family history of Primary Immunodeficiency

If you or someone you know experiences two or more of the warning signs, speak with an immunologist about the possibility of an undiagnosed Primary Immunodeficiency. Find an immunologist near you with our Find an Expert Locator.

How do I know if I have Primary Immunodeficiency?

Primary Immunodeficiency can be diagnosed in a variety of ways depending on the specific genetic defect, from blood tests to genetic sequencing.

To create understanding of the potential methods for diagnosing Primary Immunodeficiency the Jeffrey Modell Foundation developed the 4 Stages of Testing, a structured diagnostic pathway that supports physicians and care teams in accurately diagnosing Primary Immunodeficiency. 

The 4 Stages of Testing for Primary Immunodeficiency are:

1.

  • History and physical examination
  • CBC and differential
  • Quantitative Immunoglobulin levels IgG, IgM, IgA

2.

  • Specific antibody responses (tetanus, diphtheria, pneumococcus)
  • Lymphocyte surface markers CD3/CD4/CD8/CD19/CD56

3.

  • Lymphocyte proliferation studies (mitogen/antigen stimulation or skin delayed type hypersensitivity)
  • Neutrophil oxidation burst (if indicated)
  • Response to pneumococcal vaccine (for ages 3 and up)
  • Primary Immunodeficiency gene sequencing panel

4.

  • Complement screening CH50, specific complement components, AH50
  • Enzyme activity measurements (e.g. adenosine deaminase, purine nucleoside phosphorylase)
  • Phagocyte studies (e.g. surface glycoproteins, mobility, phagocytosis)
  • NK cytotoxicity studies
  • Neo antigen response to test antibody production
  • Other surface molecules for detailed immunophenotype (e.g. memory B cells, T/NK cell subpopulation)
  • Specific protein levels (e.g. SAP, Perforin, WASp)
  • Cytokine or other function receptor quantification
  • IgG subclass analysis
  • Genomic studies

Is Primary Immunodeficiency common?

It is estimated that up to 83 million people are living with Primary Immunodeficiency worldwide. However, 70-90% of them remain undiagnosed. For people with Primary Immunodeficiency, the median time from symptom onset to correct diagnosis is 4 – 9.5 years.

The Jeffrey Modell Foundation is committed to ending the diagnostic odyssey and driving earliest possible diagnosis for every person with Primary Immunodeficiency.