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Interpretive Handbook

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Test 83640 :
Streptococcus pneumoniae IgG Antibodies, 23 Serotypes, Serum

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Streptococcus pneumoniae is a gram-positive bacteria that causes a variety of infectious diseases in children and adults, including invasive disease (bacteremia and meningitis) and infections of the respiratory tract (pneumonia and otitis media).(1,2) In 2009, it is estimated that Streptococcus pneumoniae was responsible for approximately 43,500 infections and 5,000 deaths in the United States. More than 90 serotypes of Streptococcus pneumoniae have been identified, based on varying polysaccharides that are found in the bacterial cell wall. The serotypes responsible for disease vary with age and geographic location.

 

Bacterial polysaccharides induce a T-cell independent type II humoral immune. Vaccines containing bacterial polysaccharides can be effective in generating an immune response that results in production of IgG antibodies and generation of long-lived plasma and memory B cells, which can protect an individual against bacterial disease. Active immunization of adults and children >2 years is performed with nonconjugated polysaccharide vaccines (Pneumovax and Pnu-Immune 23) that contain a total of 23 serotypes, namely 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F.(3) These 23 serotypes were included because, as a group, they account for approximately 90% of invasive pneumococcal infections. Antibody responses develop in approximately 75% to 85% of nonimmunocompromised adults and older children approximately 4 to 6 weeks following immunization. Immunization with a 23-valent vaccine is recommended for all adults > or =65 years of age and for adults 18 to 64 years of age with certain chronic diseases (heart disease, lung disease, type I diabetes, liver disease), those who are immunocompromised (congenital or acquired immunodeficiencies, malignancy, solid-organ transplant), and those with functional or anatomic asplenia.(3) 

 

In contrast to adults and older pediatrics, immune responses to polysaccharide antigens in children <2 years of age are generally weak. Active immunization of children <2 years requires multiple injections of vaccine prepared from purified polysaccharides conjugated to an immunogenic carrier (Corynebacterium diphtheria strain C7 protein), which results in a T-cell dependent antibody response. Prior to the availability of routine Streptococcus pneumoniae vaccination, in children <6 years, 7 serotypes (4, 6B, 9V, 18C, 19F, and 23F) accounted for 80% of invasive disease and up to 100% of all isolates that were found to be highly resistant to treatment with penicillin. The first conjugated vaccine available for children <2 years (Prevnar) contained these 7 serotypes.(4,5) The vaccine was highly effective, with invasive disease in children less than 5 years of age reduced from 99 to 21 cases per 100,000 population from 1998 to 2008. In addition, it was demonstrated that, after Prevnar became part of the routine vaccination schedule, only 2% of invasive disease was associated with any of the serotypes present in the 7-valent conjugate vaccine. Instead, approximately 61% of the invasive disease was caused by an additional 6 serotypes, including 1, 3, 5, 6A, 7F, and 19A. This led to development of a 13-valent Streptococcus pneumoniae polysaccharide conjugate vaccine, which is marketed as Prevnar13. Prevnar13 is approved for administration to all children ages 6 weeks to 71 months, and has replaced the previous 7-valent Prevnar vaccine.(6)

 

Patients with intrinsic defects in humoral immunity, such as common variable immunodeficiency, may have impaired antibody responses to pneumococcal vaccination. Further, impaired polysaccharide responsiveness, also known as selective antibody deficiency, is a recognized clinical entity in patients >2 years and is characterized by recurrent bacterial respiratory infections, absent or subnormal antibody response to a majority of the polysaccharide antigens, and normal or increased immunoglobulin levels, including IgG subclasses, in the context of an intact humoral response to protein antigens. In several other primary immunodeficiencies, including Wiskott-Aldrich syndrome, autoimmune lymphoproliferative syndrome, and DiGeorge syndrome, IgG subclass deficiencies may also result in impaired antibody responses to polysaccharide antigens.

Useful For Suggests clinical disorders or settings where the test may be helpful

Assessing the IgG antibody response to active immunization with nonconjugated, 23-valent vaccines

 

Assessing the IgG antibody response to active immunization with conjugated, 13-valent vaccines

 

Determining the ability of an individual to produce an antibody response to polysaccharide antigen(s), as part of an evaluation for humoral or combined immunodeficiencies

Interpretation Provides information to assist in interpretation of the test results

As a general guideline, nonimmunocompromised adults develop IgG antibodies approximately 4 to 6 weeks following nonconjugated vaccination. A study conducted at the Mayo Clinic assessed IgG antibody concentrations prior to and following vaccination in a cohort of 100 healthy adults who met stringent exclusion criteria, including lack of previous pneumococcal vaccination or pneumonia associated with Streptococcus pneumoniae infection. Based on this data, reference ranges were established that most effectively discriminated between prevaccination and postvaccination antibody concentrations. Antibody concentrations greater than or equal to the reference value for at least 50% of serotypes in either a pre- or postvaccination specimen or a 2-fold or greater increase in antibody concentrations for at least 50% of serotypes when comparing the pre- to the postvaccination results would be consistent with a normal response to Streptococcus pneumoniae vaccination.

 

Serotype-specific antibodies may persist for up to 10 years following immunization or infection.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

The humoral immune response to Streptococcus pneumoniae is age dependent and the database of IgG antibody concentrations to different serotypes is incomplete.

 

Protective concentrations of IgG antibodies, or those required to prevent infection from Streptococcus pneumoniae, have not been defined for any serotype.

 

Quantitation of the IgG antibody response to pneumococcal serotypes does not provide any information on the functional capacity of the serotype-specific antibodies generated (opsonization efficiency).

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Results are reported in mcg/mL. 

Serotype

Normal Value

1 (1)

 > or =2.3

2 (2)

 > or =1.0

3 (3)

 > or =1.8

4 (4)

 > or =0.6

5 (5)

 > or =10.7

8 (8)

 > or =2.9

9N (9)

 > or =9.2

12F (12)

 > or =0.6

14 (14)

 > or =7.0

17F (17)

 > or =7.8

19F (19)

 > or =15.0

20 (20)

 > or =1.3

22F (22)

 > or =7.2

23F (23)

 > or =8.0

6B (26)

 > or =4.7

10A (34)

 > or =2.9

11A (43)

 > or =2.4

7F (51)

 > or =3.2

15B (54)

 > or =3.3

18C (56)

 > or =3.3

19A (57)

 > or =17.1

9V (68)

 > or =2.6

33F (70)

 > or =1.7

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Weisberg SS: Pneumococcus. Dis Mon 2007 October;53(10):495-502

2. Braido F, Bellotti M, De Maria A, et al: The role of pneumococcal vaccine. Pulm Pharm Ther 2008 August;21(4):608-615

3. Nuorti JP, Whitney CG: Updated recommendations for prevention of invasive pneumococcal disease among adults using the 23-valent pneumococcal polysaccharide vaccine (PPSV23). MMWR 2010 September;59(34)1102-1106

4. Moffitt KL, Malley R: Next generation pneumococcal vaccines. Curr Opin Immunol 2011 June;23(3):407-413

5. Paradiso PR: Advances in pneumococcal disease prevention: 13-valent pneumococcal conjugate vaccine for infants and children. Clin Infect Dis 2011 May;52(10):1241-1247

6. Nuorti JP, Whitney CG: Prevention of pneumococcal disease among infants and children-Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine. MMWR Recomm Rep 2010 December;59(RR-11):1-18

7. Jacob GL, Homburger HA: Simultaneous Quantitative Measurement of IgG Antibodies to Streptococcus Pneumoniae Serotypes by Microsphere Photometry. J Allergy Clin Immunol,2004;113(2) Suppl (Abstract 1049, pS288)

8. Plikaytis BD, Holder PF, Pais LB, et al: Determination of parallelism and nonparallelism in bioassay dilution curves. J Clin Microbiology 1994 October;32:2441-2447

9. Plikaytis BD, Goldblatt D, Frasch CE, et al: An analytical model applied to a multicenter pneumococcal enzyme-linked immunosorbent assay study. J Clin Microbiol 2000 June;38(6):2043-2050

10. Park MA, Snyder MR, Smith C, et al: New guidelines for interpretation of IgG pneumococcal antibody data: results from a cohort study of healthy adults. Clin Immunol 2010 May;135(2):38


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