title: Clinical Sindbis alphavirus infection is associated with HLA-DRB1*01 allele and production of autoantibodies.
abstract: BACKGROUND
  Sindbis virus (SINV) is a mosquito-borne alphavirus found in Eurasia, Africa, and Oceania. Clinical SINV infection, characterized by arthropathic disease that may persist for years, is primarily reported in Northern Europe where the disease has considerable public health importance in endemic areas. The aim of this study was to investigate the role of genetic factors in the susceptibility and outcome of SINV infection and to elucidate the association between SINV infection and autoimmunity.
  
  
  METHODS
  The study included 49 patients with serologically confirmed symptomatic SINV infection who were followed for 3 years after acute infection. Human leukocyte antigen (HLA) genes known to be associated with rheumatic and infectious diseases and complement C4 genes were determined in 35 patients. Furthermore, a set of autoantibodies was measured at the acute phase and 3 years after infection in 44 patients.
  
  
  RESULTS
  The frequency of DRB1*01 was significantly higher among patients with SINV infection than in the reference population (odds ratio, 3.3; 95% confidence interval, 1.7-6.5; P = .003). The DRB1*01 allele was particularly frequent in patients who at 3 years postinfection experienced joint manifestations. The frequency of rheumatoid factor at 3 years postinfection was 29.5% and had increased significantly (P = .02) during the 3-year period. In addition, antinuclear and antimitochondrial antibodies were present in serum 3 years postinfection with frequencies of 15.9% and 6.8%, respectively.
  
  
  CONCLUSIONS
  Our data show that symptomatic SINV infection is associated with the HLA system and that autoantibody titers are elevated in patients 3 years postinfection. These findings indicate that SINV-induced arthritis shares features with autoimmune diseases.
authors.affiliation: Infection Biology Research Program, Department of Virology, Haartman Institute, Faculty of Medicine, University of Helsinki, Finland. jussi.sane@helsinki.fi
authors.forename: Jussi
authors.initials: J
authors.lastname: Sane
authors.forename: Satu
authors.initials: S
authors.lastname: Kurkela
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Lokki
authors.forename: Aaro
authors.initials: A
authors.lastname: Miettinen
authors.forename: Tapani
authors.initials: T
authors.lastname: Helve
authors.forename: Antti
authors.initials: A
authors.lastname: Vaheri
authors.forename: Olli
authors.initials: O
authors.lastname: Vapalahti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D018354:Alphavirus Infections / Q000235:genetics* / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D003181:Complement C4 / Q000235:genetics; D005060:Europe; D005260:Female; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012845:Sindbis Virus / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D003181:Complement C4; D059811:HLA-DRB1 Chains