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Pneumococcal vaccination in inflammatory rheumatic disease. Antibody response and protection against infections.

Nagel, Johanna LU (2018) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2018(43).
Abstract
Abstract

Objectives: Patients with inflammatory rheumatic diseases (IRDs) have higher risk of serious infections than healthy individuals due to their illness, comorbidities and treatments. Streptococcus pneumoniae is responsible for 30-50% of community aquired pneumonia in Europe.The proportion of patients with IRD receiving vaccination against pneumococci is still estimated to be suboptimal. The aims of this project was to investigate whether pneumococcal conjugated vaccination of patients with IRD leads to an antibody response adequate enough to protect against infections, and what treatments and/or other factors that influences the immunological and clinical response to vaccination.
Methods: Patients suffering from... (More)
Abstract

Objectives: Patients with inflammatory rheumatic diseases (IRDs) have higher risk of serious infections than healthy individuals due to their illness, comorbidities and treatments. Streptococcus pneumoniae is responsible for 30-50% of community aquired pneumonia in Europe.The proportion of patients with IRD receiving vaccination against pneumococci is still estimated to be suboptimal. The aims of this project was to investigate whether pneumococcal conjugated vaccination of patients with IRD leads to an antibody response adequate enough to protect against infections, and what treatments and/or other factors that influences the immunological and clinical response to vaccination.
Methods: Patients suffering from different forms of arthritis or systemic lupus erythematosus with different ongoing antirheumatic treatments were vaccinated with pneumococcal vaccine; 7- or 13-valent. Antibody response was analyzed using several laboratory methods; standard ELISA, multiplex fluorescent microsphere immunoassay and Opsonophagocytic assay. Skåne Healthcare Register was searched for ICD-codes corresponding to pneumococcal infections. Circulating plasmablasts from RA patients with or without methotrexate were isolated using ELISPOT.
Results: Arthritis patients who received 7-valent conjugated pneumococcal vaccine had a relative risk reduction of being diagnosed with a pneumococcal infection up to 4 years after the injection. Antibody levels of approximately 1 µg/ml or above was associated with reduced risk of infection. Higher age and oral prednisolone treatment at vaccination predicted an elevated risk of serious infection after vaccination. Patients with rheumatoid arthritis with methotrexate treatment presented lower antibody levels but equal numbers of vaccine-specific antibody-producing plasmablasts in comparison with patients without methotrexate. SLE patients on belimumab in addition to standard treatment did not show impaired antibody response of 12 measured serotype specific antibodies, compared to SLE patients on standard of care treatment.
Conclusion. Patients with arthritis or SLE have in most cases an adequate antibody response after conjugated pneumococcal vaccination, although reduced in comparison to healthy controls. There is a correlation between reduced antibody response after vaccination and higher risk of subsequent serious pneumococcal infections. Vaccination leads to a relative risk reduction of pneumococcal infection. Belimumab does not seem to affect antibody response. The antibody response among patients on methotrexate is reduced, but this does not seem to be caused by a reduced number of antibody secreting cells.
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author
supervisor
opponent
  • professor Elkayem, Ori, Department of Rheumatology, Tel Aviv Medical Center and Sackler Faculty of Medicine
organization
publishing date
type
Thesis
publication status
published
subject
keywords
vaccination, pneumococci, inflammatory rheumatic disease
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2018
issue
43
pages
78 pages
publisher
Lund University: Faculty of Medicine
defense location
Reumatologiska klinikens föreläsningssal, Lottasalen, Universitetssjukhuset i Lund
defense date
2018-05-03 13:00:00
ISSN
1652-8220
ISBN
978-91-7619-610-6
language
English
LU publication?
yes
additional info
ISSN: 1652-8220 Lund University, Faculty of Medicine Doctoral Dissertation Series 2018:43
id
04efb07a-48ef-4b09-a4eb-b164c129225f
date added to LUP
2018-04-10 12:53:41
date last changed
2019-11-19 13:49:35
@phdthesis{04efb07a-48ef-4b09-a4eb-b164c129225f,
  abstract     = {Abstract<br/><br/>Objectives: Patients with inflammatory rheumatic diseases (IRDs) have higher risk of serious infections than healthy individuals due to their illness, comorbidities and treatments. Streptococcus pneumoniae is responsible for 30-50% of community aquired pneumonia in Europe.The proportion of patients with IRD receiving vaccination against pneumococci is still estimated to be suboptimal. The aims of this project was to investigate whether pneumococcal conjugated vaccination of patients with IRD leads to an antibody response adequate enough to protect against infections, and what treatments and/or other factors that influences the immunological and clinical response to vaccination.   <br/>Methods: Patients suffering from different forms of arthritis or systemic lupus erythematosus  with different ongoing antirheumatic treatments were vaccinated with pneumococcal vaccine; 7- or 13-valent. Antibody response was analyzed using several laboratory methods; standard ELISA, multiplex fluorescent microsphere immunoassay and Opsonophagocytic assay. Skåne Healthcare Register was searched for ICD-codes corresponding to pneumococcal infections. Circulating plasmablasts from RA patients with or without methotrexate were isolated using ELISPOT. <br/>Results: Arthritis patients who received 7-valent conjugated pneumococcal vaccine had a relative risk reduction of being diagnosed with a pneumococcal infection up to 4 years after the injection. Antibody levels of approximately 1 µg/ml or above was associated with reduced risk of  infection. Higher age and oral prednisolone treatment at vaccination predicted an elevated risk of serious infection after vaccination. Patients with rheumatoid arthritis with methotrexate treatment presented lower antibody levels but equal numbers of vaccine-specific antibody-producing plasmablasts in comparison with patients without methotrexate. SLE patients on belimumab in addition to standard treatment did not show impaired antibody response of 12 measured serotype specific antibodies, compared to SLE patients on standard of care treatment.<br/>Conclusion. Patients with arthritis or SLE have in most cases an adequate antibody response after conjugated pneumococcal vaccination, although reduced in comparison to healthy controls. There is a correlation between reduced antibody response after vaccination and higher risk of subsequent serious pneumococcal infections. Vaccination leads to a relative risk reduction of pneumococcal infection.  Belimumab does not seem to affect antibody response. The antibody response among patients on methotrexate is reduced, but this does not seem to be caused by a reduced number of antibody secreting cells.<br/>},
  author       = {Nagel, Johanna},
  isbn         = {978-91-7619-610-6},
  issn         = {1652-8220},
  language     = {eng},
  number       = {43},
  publisher    = {Lund University: Faculty of Medicine},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Pneumococcal vaccination in inflammatory rheumatic disease. Antibody response and protection against infections.},
  url          = {https://lup.lub.lu.se/search/ws/files/41344872/elektronisk.kappa.johanna.nagel.pdf},
  volume       = {2018},
  year         = {2018},
}