title: Immunogenicity of influenza H1N1 vaccination in mixed connective tissue disease: effect of disease and therapy.
abstract: OBJECTIVE
  To assess the potential acute effects regarding the immunogenicity and safety of non-adjuvanted influenza A H1N1/2009 vaccine in patients with mixed connective tissue disease and healthy controls.
  
  
  METHODS
  Sixty-nine mixed connective tissue disease patients that were confirmed by Kasukawa's classification criteria and 69 age- and gender-matched controls participated in the study; the participants were vaccinated with the non-adjuvanted influenza A/California/7/2009 (H1N1) virus-like strain. The percentages of seroprotection, seroconversion, geometric mean titer and factor increase in the geometric mean titer were calculated. The patients were clinically evaluated, and blood samples were collected pre- and 21 days post-vaccination to evaluate C-reactive protein, muscle enzymes and autoantibodies. Anti-H1N1 titers were determined using an influenza hemagglutination inhibition assay. ClinicalTrials.gov: NCT01151644.
  
  
  RESULTS
  Before vaccination, no difference was observed regarding the seroprotection rates (p = 1.0) and geometric mean titer (p = 0.83) between the patients and controls. After vaccination, seroprotection (75.4% vs. 71%, (p = 0.7), seroconversion (68.1% vs. 65.2%, (p = 1.00) and factor increase in the geometric mean titer (10.0 vs. 8.0, p = 0.40) were similar in the two groups. Further evaluation of seroconversion in patients with and without current or previous history of muscle disease (p = 0.20), skin ulcers (p = 0.48), lupus-like cutaneous disease (p = 0.74), secondary Sjogren syndrome (p = 0.78), scleroderma-pattern in the nailfold capillaroscopy (p = 1.0), lymphopenia #1000/mm³ on two or more occasions (p = 1.0), hypergammaglobulinemia $1.6 g/d (p = 0.60), pulmonary hypertension (p = 1.0) and pulmonary fibrosis (p = 0.80) revealed comparable rates. Seroconversion rates were also similar in patients with and without immunosuppressants. Disease parameters, such as C-reactive protein (p = 0.94), aldolase (p = 0.73), creatine phosphokinase (p = 0.40) and ribonucleoprotein antibody levels (p = 0.98), remained largely unchanged pre and post-vaccination. No severe side effects were reported.
  
  
  CONCLUSIONS
  The non-adjuvanted influenza A/H1N1 vaccination immune response in mixed connective tissue disease patients is adequate and does not depend on the disease manifestations and therapy.
authors.affiliation: Division of Rheumatology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Renata
authors.initials: R
authors.lastname: Miossi
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fuller
authors.forename: Júlio C B
authors.initials: JC
authors.lastname: Moraes
authors.forename: Ana Cristina M
authors.initials: AC
authors.lastname: Ribeiro
authors.forename: Carla G S
authors.initials: CG
authors.lastname: Saad
authors.forename: Nadia E
authors.initials: NE
authors.lastname: Aikawa
authors.forename: Joao L
authors.initials: JL
authors.lastname: Miraglia
authors.forename: Maria A
authors.initials: MA
authors.lastname: Ishida
authors.forename: Eloisa
authors.initials: E
authors.lastname: Bonfa
authors.forename: M Teresa C
authors.initials: MT
authors.lastname: Caleiro
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D008947:Mixed Connective Tissue Disease / Q000276:immunology*; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D007252:Influenza Vaccines