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Increased serum bactericidal activity of autologous serum in C2 deficiency after vaccination against Haemophilus influenzae type b, and further support for an MBL-dependent C2 bypass mechanism

Jönsson, Göran LU ; Hansson, Christina LU ; Mellhammar, Lisa LU ; Gullstrand, Birgitta LU ; Bengtsson, Anders A. LU ; Sahl, Cecilia LU orcid and Skattum, Lillemor LU (2021) In Vaccine 39(8). p.1297-1302
Abstract

Deficiencies of C2 and other components of the classical pathway of complement are associated with increased risk of infections with encapsulated bacteria, such as Haemophilus (H.) influenzae. Defense against H. influenzae is dependent on specific antibodies and complement, which mediate serum bactericidal activity (SBA) and opsonization. Due to lack of normal classical and lectin complement pathway function in C2 deficiency (C2D), SBA would have to depend either on the alternative pathway or on C2 bypass mechanisms. Here we studied SBA against H. influenzae type b (Hib) before and after vaccination in a group of C2-deficient persons, as the bactericidal capacity of antibodies in autologous complement in relation to vaccination has not... (More)

Deficiencies of C2 and other components of the classical pathway of complement are associated with increased risk of infections with encapsulated bacteria, such as Haemophilus (H.) influenzae. Defense against H. influenzae is dependent on specific antibodies and complement, which mediate serum bactericidal activity (SBA) and opsonization. Due to lack of normal classical and lectin complement pathway function in C2 deficiency (C2D), SBA would have to depend either on the alternative pathway or on C2 bypass mechanisms. Here we studied SBA against H. influenzae type b (Hib) before and after vaccination in a group of C2-deficient persons, as the bactericidal capacity of antibodies in autologous complement in relation to vaccination has not been investigated at group level in C2D. Sera from 22 persons with C2D and 26 healthy controls were available. Out of these, 18 persons with C2D and all controls had been vaccinated with Act-HIB®. SBA against Hib bacteria was analyzed with autologous serum as the only complement source. Antibodies to Hib capsular polysaccharide had been analyzed previously. Concentrations of mannose-binding lectin (MBL) and other complement components were measured in serum. SBA of both C2-deficient persons and controls was significantly more efficient after vaccination (p = 0.002 and p < 0.0001, respectively). After vaccination, all but two C2-deficient sera and one control serum showed sufficient SBA (<50% surviving bacteria). Before vaccination, SBA of C2-deficient sera was negatively correlated to serum concentrations of MBL (lower proportion of surviving bacteria with higher MBL concentration; r = −0.55, p = 0.008). After vaccination, SBA of C2-deficient sera was negatively correlated to serum concentrations of IgG Hib antibodies (r = −0.56, p = 0.01). In conclusion, SBA against Hib in autologous serum is increased after vaccination in persons with C2D. In unvaccinated C2-deficient persons SBA was correlated to MBL concentration, providing further support for an MBL-dependent C2 bypass mechanism operating in C2D.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
C2 bypass, C2 deficiency, Haemophilus influenzae type b vaccination, Mannose-binding lectin, Serum bactericidal activity
in
Vaccine
volume
39
issue
8
pages
6 pages
publisher
Elsevier
external identifiers
  • scopus:85099854436
  • pmid:33509693
ISSN
0264-410X
DOI
10.1016/j.vaccine.2021.01.007
language
English
LU publication?
yes
id
903663b1-2f77-4c9a-8498-b5c612dfdccb
date added to LUP
2021-12-27 15:04:59
date last changed
2024-03-23 16:39:14
@article{903663b1-2f77-4c9a-8498-b5c612dfdccb,
  abstract     = {{<p>Deficiencies of C2 and other components of the classical pathway of complement are associated with increased risk of infections with encapsulated bacteria, such as Haemophilus (H.) influenzae. Defense against H. influenzae is dependent on specific antibodies and complement, which mediate serum bactericidal activity (SBA) and opsonization. Due to lack of normal classical and lectin complement pathway function in C2 deficiency (C2D), SBA would have to depend either on the alternative pathway or on C2 bypass mechanisms. Here we studied SBA against H. influenzae type b (Hib) before and after vaccination in a group of C2-deficient persons, as the bactericidal capacity of antibodies in autologous complement in relation to vaccination has not been investigated at group level in C2D. Sera from 22 persons with C2D and 26 healthy controls were available. Out of these, 18 persons with C2D and all controls had been vaccinated with Act-HIB®. SBA against Hib bacteria was analyzed with autologous serum as the only complement source. Antibodies to Hib capsular polysaccharide had been analyzed previously. Concentrations of mannose-binding lectin (MBL) and other complement components were measured in serum. SBA of both C2-deficient persons and controls was significantly more efficient after vaccination (p = 0.002 and p &lt; 0.0001, respectively). After vaccination, all but two C2-deficient sera and one control serum showed sufficient SBA (&lt;50% surviving bacteria). Before vaccination, SBA of C2-deficient sera was negatively correlated to serum concentrations of MBL (lower proportion of surviving bacteria with higher MBL concentration; r = −0.55, p = 0.008). After vaccination, SBA of C2-deficient sera was negatively correlated to serum concentrations of IgG Hib antibodies (r = −0.56, p = 0.01). In conclusion, SBA against Hib in autologous serum is increased after vaccination in persons with C2D. In unvaccinated C2-deficient persons SBA was correlated to MBL concentration, providing further support for an MBL-dependent C2 bypass mechanism operating in C2D.</p>}},
  author       = {{Jönsson, Göran and Hansson, Christina and Mellhammar, Lisa and Gullstrand, Birgitta and Bengtsson, Anders A. and Sahl, Cecilia and Skattum, Lillemor}},
  issn         = {{0264-410X}},
  keywords     = {{C2 bypass; C2 deficiency; Haemophilus influenzae type b vaccination; Mannose-binding lectin; Serum bactericidal activity}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{1297--1302}},
  publisher    = {{Elsevier}},
  series       = {{Vaccine}},
  title        = {{Increased serum bactericidal activity of autologous serum in C2 deficiency after vaccination against Haemophilus influenzae type b, and further support for an MBL-dependent C2 bypass mechanism}},
  url          = {{http://dx.doi.org/10.1016/j.vaccine.2021.01.007}},
  doi          = {{10.1016/j.vaccine.2021.01.007}},
  volume       = {{39}},
  year         = {{2021}},
}