Home > About Primary Immunodeficiency (PI) > Diagnosis and Treatment

Diagnosis and Treatment

Barriers to Diagnosis

Severe defects may be recognized early in childhood, but many forms may go undiagnosed into adolescence or adulthood.1 According to a survey by the IDF reported in 2007 among 1300 people with PI, the average time from symptom onset to diagnosis is 12.4 years.2



Factors that have contributed to underdiagnosis and delays in diagnosis of PI include:

  • lack of awareness3
  • variable and complex presentation of PI4
  • masking of symptoms with antibiotic use5
  • absence of family history2

Identifying PI

Antibody production defects account for more than half (51.6%) of all primary immunodeficiency cases, making them the most common forms of PI.6

Signs and symptoms suggestive of an antibody production defect include, but are not limited to3,7:

  • Recurrent sinopulmonary infections
    • Otitis media
    • Sinusitis*
    • Bronchitis
    • Pneumonia**
      *documented by X-ray or CT scan
      **with fever
  • Gastrointestinal infections
    • Recurrent/chronic diarrhea
  • Autoimmune disorders
  • Allergic conditions
  • Skin infections
  • Meningitis and/or sepsis

Importance of Early Detection

If left untreated, the infections and conditions characteristic of PI may lead to:

  • Bronchiectasis8,9
  • Loss of lung function2
  • Chronic diarrhea, and malabsorption resulting in impairment of digestive function2,10
  • Hearing impairment2
  • Hospitalizations9,11
  • Frequent days missed from work or school11
  • Frequent, prolonged and/or intravenous antibiotic use12,5

The longer the time to diagnosis from symptom onset, the greater the number of permanent functional impairments in patients with PI.2

Diagnosing PI

If you suspect an antibody production defect, conduct an immunological evaluation for patients.7 As you begin the diagnostic process, consider:

  • Beginning with a thorough medical history and physical exam
  • Including a complete blood count (CBC) with manual differential

The initial laboratory examination of antibody production defects consists of measuring the Quantity and Quality of antibodies.8

Quantitative Measurement Qualitative Measurement
The measurement of the concentration of IgG, IgM, and IgA in serum:
  • Levels below the normal range for a patient raise the index of suspicion for an antibody production defect8
  • Normal levels may also be found with some types of antibody production defects13
The measurement of the antibody response to the antigenic challenge of vaccines:
  • Protein (e.g., diphtheria and tetanus): T-dependent antigens requiring T- and B-cell cooperation14
  • Polysaccharide (pneumococcal): T-independent antigens. This serves 2 purposes:
    • To determine patient’s capability of mounting protective antibody responses14
    • To determine the magnitude of the response14

Treatment of PI

Antibody treatment, the use of IgG concentrates administered intravenously (IV) or subcutaneously (SC), is an important treatment option for patients who are unable to produce adequate amounts of antibodies or whose antibodies cannot mount a protective immune response. The IgG product, prepared from large pools of human plasma to assure a broad spectrum of antibodies, is known as immunoglobulin or immune serum globulin. IV and SC IgG are used to treat many different types of primary immunodeficiency (PI).

Learn more about one type of lgG treatment, GAMMAGARD LIQUID.

References: 1. National Institute of Child Health & Human Development. Primary Immunodeficiency: when the body’s defenses are missing. http://nichd.nih.gov/publications/pubs/primary_immuno.cfm?renderforprint=1. Updated April 7, 2008. Accessed May 17, 2013. 2. Immune Deficiency Foundation. Primary immune deficiency diseases in America: 2007. The third national survey of patients. http://primaryimmune.org/idf- survey-research-center/idf-surveys?aid=1264&sa=1. Published May 1, 2009. Accessed May 17, 2013. 3. Wood P, Stanworth S, Burton J, et al; for the UK Primary Immunodeficiency Network. Recognition, clinical diagnosis and management of patients with primary antibody deficiencies: a systematic review. Clin Exp Immunol. 2007;149(3):410-423. 4. Eades-Perner A-M, Gathmann B, Knerr V, et al. The European internet-based patient and research database for primary immunodeficiencies: results 2004-06. Clin Exp Immunol. 2007;147(2):306-312. 5. Verbsky JW, Grossman WJ. Cellular and genetic basis of primary immune deficiencies. Pediatric Clin North Am. 2006;53(4):649-684. 6. Modell V, Gee B, Lewis DB, et al. Global study of primary immunodeficiency diseases (PI)—diagnosis, treatment, and economic impact: an updated report from the Jeffrey Modell Foundation. Immunol Res. 2011;51(1):61-70. 7. Immune Deficiency Foundation. Immune Deficiency Foundation Diagnostic and Clinical Care Guidelines for Primary Immunodeficiency Diseases. 2nd ed. Towson, MD: Immune Deficiency Foundation; 2008, 2009. http://primaryimmune.org/about-primary-immunodeficiency-diseases/idf-publications?aid=379&pid=275&sa=1. Accessed May 17, 2013. 8. Bonilla FA, Bernstein IL, Khan DA, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. Ann Allergy Asthma Immunol. 2005;94(5 suppl 1):S1-S63. 9. Seymour B, Miles J, Haeney M. Primary antibody deficiency and diagnostic delay. J Clin Pathol. 2005;58(5):546-547. 10. Kobrynski LJ, Mayer L. Diagnosis and treatment of primary immunodeficiency disease in patients with gastrointestinal symptoms. Clin Immunol. 2011;139(3):238-48. 11. Modell F, Puente D, Modell V. From genotype to phenotype. Further studies measuring the impact of a Physician Education and Public Awareness Campaign on early diagnosis and management of primary immunodeficiencies. Immunol Res. 2009;44(1-3):132-149. 12. Jeffrey Modell Foundation Medical Advisory Board. 10 warning signs of primary immunodeficiency for adults. http://www.info4pi.org/aboutPI/pdf/
General10WarningSignsFINAL.pdf. Published 2009. Accessed May 17, 2013. 13. Orange JS. The Clinical Focus on Clinical Update in Immunoglobulin Therapy for Primary Immunodeficiency Diseases. Towson, MD: Immune Deficiency Foundation: 2011. 14. Orange JS, Ballow M, Stiehm ER, et al. Use and interpretation of diagnostic vaccination in primary immunodeficiency: a working group report of the Basic and Clinical Immunolody Interest Section of the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol. 2012;130(suppl 3):S1-24.


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