title: The association between antibody levels before and after 7-valent pneumococcal conjugate vaccine immunization and subsequent pneumococcal infection in chronic arthritis patients.
abstract: BACKGROUND
  The aim of present study is to inverstigate the association between antibody levels after vaccination with 7-valent pneumococcal conjugate vaccine (PCV7) and subsequent serious pneumococcal infections in rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients.
  
  
  METHODS
  A cohort of 497 patients (RA=248 and SpA=249) received a single dose of PCV7. At vaccination, patients were treated with methotrexate (MTX; n=85), anti-tumour necrosis factor (anti-TNF) + MTX (n=169), anti-TNF monotherapy (n=158) and non-steroidal anti-inflammatory drugs (NSAIDs)/analgesics (n=85). Antibody levels of serotypes 6B and 23B were analyzed before and 4 to 6 weeks after vaccination using standard enzyme-linked immunosorbent assay (ELISA). Serious pneumococcal infections (pneumonia/lower respiratory tract infection, meningitis, sepsis, septic arthritis) occurring within 4.5 years after vaccination were identified in the Skåne Healthcare Register using the International Classification of Diseases, tenth revision (ICD-10) codes. The association between post-vaccination antibody levels and protection against infections and determination of protective cutoff levels was explored using receiver operating characteristic (ROC) curves. Predictors of infection were studied using regression analyses.
  
  
  RESULTS
  Eighteen infections were registered in 15 patients before vaccination and 27 infections in 23 patients after vaccination. Patients with serious infections after vaccination had significantly lower post-vaccination antibody titres for both 6B (P=0.04) and 23 F (P=0.04). Post-vaccination antibody levels of at least 1.29 mg/L and 1.01 mg/L for 6B and 23, respectively, were associated with better protection from serious infections. Higher age, concomitant prednisolone but not MTX or anti-TNF were associated with such infections.
  
  
  CONCLUSIONS
  Patients with more robust antibody responses after vaccination with pneumococcal conjugate vaccine were less likely to suffer from serious infections. High age and prednisolone at vaccination were associated with putative serious pneumococcal infections in this cohort.
  
  
  BACKGROUND
  EudraCT EU 2007-006539-29 and NCT00828997 . Registered 23 January 2009.
authors.affiliation: Department of Clinical Sciences, Lund, Section of Rheumatology, Lund University, and Skåne University Hospital, Kioskgatan 3, SE-221 85, Lund, Sweden. johanna.bengtsson.nagel@gmail.com.
authors.forename: Johanna
authors.initials: J
authors.lastname: Nagel
authors.affiliation: Department of Clinical Sciences, Lund, Section of Rheumatology, Lund University, and Skåne University Hospital, Kioskgatan 3, SE-221 85, Lund, Sweden. pierre.geborek@med.lu.se.
authors.forename: Pierre
authors.initials: P
authors.lastname: Geborek
authors.affiliation: Department of Clinical Sciences, Lund, Section of Rheumatology, Lund University, and Skåne University Hospital, Kioskgatan 3, SE-221 85, Lund, Sweden. tore.saxne@med.lu.se.
authors.forename: Tore
authors.initials: T
authors.lastname: Saxne
authors.affiliation: Department of Clinical Sciences Lund, Section of Infectious Diseases, Lund University and Skåne University Hospital, Kioskgatan 3, SE-221 85, Lund, Sweden. goran.b.jonsson@skane.se.
authors.forename: Göran
authors.initials: G
authors.lastname: Jönsson
authors.affiliation: Epidemiology and Register Centre South, Skåne University Hospital, Lund, and Orthopaedics, Department of Clinical Sciences Lund, Lund University, Barngatan 2B, Lund, SE-221 85, Sweden. martin.englund@med.lu.se.|Clinical Epidemiology Research & Training Unit, Boston University School of Medicine, 650 Albany Street, Boston, MA, 02118, USA. martin.englund@med.lu.se.
authors.forename: Martin
authors.initials: M
authors.lastname: Englund
authors.affiliation: Epidemiology and Register Centre South, Skåne University Hospital, Lund, and Orthopaedics, Department of Clinical Sciences Lund, Lund University, Barngatan 2B, Lund, SE-221 85, Sweden. ingemar.petersson@med.lu.se.
authors.forename: Ingemar F
authors.initials: IF
authors.lastname: Petersson
authors.affiliation: Department of Clinical Sciences, Lund, Section of Rheumatology, Lund University, and Skåne University Hospital, Kioskgatan 3, SE-221 85, Lund, Sweden. jan-ake.nilsson@med.lu.se.
authors.forename: Jan-Åke
authors.initials: JÅ
authors.lastname: Nilsson
authors.affiliation: Department of Laboratory Medicine, Section of Microbiology and Immunology, Lund University, Sölvegatan 23, Lund, SE-223 62, Sweden. lennart.truedsson@med.lu.se.
authors.forename: Lennart
authors.initials: L
authors.lastname: Truedsson
authors.affiliation: Department of Clinical Sciences, Lund, Section of Rheumatology, Lund University, and Skåne University Hospital, Kioskgatan 3, SE-221 85, Lund, Sweden. meliha.c_kapetanovic@med.lu.se.
authors.forename: Meliha C
authors.initials: MC
authors.lastname: Kapetanovic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000097:blood*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000150:complications* / Q000276:immunology; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000069443:Heptavalent Pneumococcal Conjugate Vaccine / Q000627:therapeutic use*; D006801:Humans; D007114:Immunization / Q000379:methods*; D007155:Immunologic Factors / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011008:Pneumococcal Infections / Q000150:complications / Q000382:microbiology / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D007155:Immunologic Factors