How to test the ability to develop humoral and cellular immune response?

A patient with suspected CVID can be tested for the ability to develop humoral and cellular immune response as follows:

1. Humoral immune response.


Inject patient with Pneumovax 23 (not Prevnar, which is a 7-valent conjugate vaccine). Check anti-polysaccharide IgG antibody to pneumococcus serotypes in 3 weeks.

Which serotypes should be included in the order for Ig?


The same serotypes that were included in the given vaccine. Check the enclosed leaflet for this information. For example, the serotypes included in Pneumovax 23 can be found from the Merck website (PDF):

1 2 3 4 5 6B 7F 8 9N 9V 10A 11A 12F 14 15B 17F 18C 19F 19A 20 22F 23F 33F

How to collect the serum for anti-polysaccharide IgG antibodies?


Collect the serum prior to immunization with Pneumovax 23. Store the pre-immunization serum in the office refrigerator. Give the vaccine. Check the post-immunization serum 3 weeks later. Send both pre- and post-immunization serums to the laboratory at the same time.

The pneumococcal vaccine comprises purified capsular polysaccharide of 23 stereotypes that account for more than 90% of the invasive pneumococcal infections in the USA. It induces adequate anti-polysaccharide IgG antibody levels to most or all of the component polysaccharide antigens in immunocompetent adults. Elderly adults respond about equally well to vaccination as do younger adults. The current 23-valent vaccine comprises 25 μg of each of 23 pneumococcal stereotypes (namely, serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F and 33F).

Heptavalent pneumococcal conjugate vaccine (PCV7) targets only 7 of the more than 92 pneumococcal serotypes. Lancet, 2011.

What is a normal response to pneumococcal immunization? 

Protection against infection and colonization is associated with specific IgG concentrations of 1.3 mcg/ml.

A second component in judging response is the final concentration of antibodies after immunization regardless of increase from preimmunization concentration. An adequate response is a post-immunization antibody concentration of more than 1.3 mcg/ml, even in the absence of a fourfold increase.

Children 2 to 5 years of age are normally expected to have an adequate response to more than 50% of serotypes tested. Patients 6 years or older are normally expected to respond to more than 70% of the serotypes tested. Source: Assessment and clinical interpretation of polysaccharide antibody responses. Kenneth Paris and Ricardo Sorensen. Annals of Allergy, Asthma, and Immunology, 2007; volume 99, Issue 5, Pages 462-464, and AAAAI Ask the Expert, 2012.


2. Cellular immune response.


Some patients with CVID have decreased cell immunity as well. Cell immunity is tested by anergy panel with common antigens to which the patient was likely exposed in the past: Tetanus toxoid, Trichophyton, Candida. The test is read in 48-72 hours. Flow cytometry should also be ordered.

Read more in How to Diagnose Common Variable Immunodeficiency (CVID)?

References:

Antibody response of pneumococcal vaccine: need for booster dosing? International Journal of Antimicrobial Agents, Volume 14, Issue 2, March 2000, Pages 107-112.
How to identify a possible specific antibody deficiency to pneumococcus. AAAAI, 2007.
Heptavalent pneumococcal conjugate vaccine (PCV7) targets only 7 of the more than 92 pneumococcal serotypes. Lancet, 2011.
Cost-effectiveness of Pneumococcal Conjugate Vaccine vs. Polysaccharide Vaccine in Adults: PCV13 was better than PPSV23. JAMA, 2012.

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