A novel mutation in the C3 gene and recurrent invasive pneumococcal infection: a clue for vaccine development.

Abstract

BACKGROUND:

We identified a 4 year-old boy born to a consanguineous marriage with C3 deficiency after three episodes of invasive pneumococcal disease. The efficacy of anti-pneumococcal vaccination in C3 deficient patients is not clear.

OBJECTIVES:

Our objective was to identify the genetic defect resulting in his C3 deficiency and measure his ability to mount an adaptive immune response.

METHODS:

Fibroblast cell lines were generated from the patient and parents. DNA was isolated and the C3 gene sequenced. Quantitation of C3 expression was performed by immunoprecipitation of (35)S-methionine labeled protein. Isotype specific anti-pneumococcal antibodies present in the patients sera was quantitated after administration of Prevnar-7 and Pneumovax vaccines.

RESULTS:

Pneumococcal types 14, 10B and 29 were identified from the blood on three separate occasions over a period of 20 months. C3 levels in the blood was <10, 71, and 66 for the patient, mother and father, respectively (90-180mg/dl, normal). Sequencing revealed a homozygous deletion of one nucleotide located in exon 31 (delA in position 3997 of cDNA) which resulted in a transcriptional stop signal thirteen codons later. The parents were heterozygous for the mutation. No detectable C3 was noted by immunoprecipitation. The patient mounted adequate antibody responses to the protein-conjugated Prevnar and tetanus vaccines but not to the polysaccharide antigen based Pneumovax vaccine. Major immunoglobulin class levels were normal.

CONCLUSION:

C3 deficiency results in the selective impairment to mount a response against polysaccharide-based antigens. Protein-conjugated vaccines are likely to be efficacious in immunizing against encapsulated organisms in these patients.

• Authors: Michael Goldberg, Véronique Fremeaux-Bacchi, Penina Koch, Zvi Fishelson, Yitzhak Katz
• Journal: Molecular immunology (Mol Immunol) Vol. 48 Issue 15-16 Pg. 1926-31 (Sep 2011) ISSN: 1872-9142 [Electronic] England
• PMID: 21676463 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Complement C3
• Pneumococcal Vaccines

Topics

• Base Sequence
• Child, Preschool
• Complement C3 (deficiency, genetics)
• DNA Mutational Analysis
• Enzyme-Linked Immunosorbent Assay
• Humans
• Immunoprecipitation
• Male
• Molecular Sequence Data
• Pneumococcal Vaccines (immunology)
• Pneumonia, Pneumococcal (genetics, immunology)
• Point Mutation