title: A transient peak of infections during onset of rheumatoid arthritis: a 10-year prospective cohort study.
abstract: OBJECTIVE
  The role of infection in rheumatoid arthritis (RA) has not been determined. We aimed to document the infectious burden and some aspects of antibacterial immunity in a large and prospective cohort study of RA patients in the early and late stages of the disease and in their relatives predisposed to RA.
  
  
  METHODS
  Clinical and laboratory examination of all individuals enrolled in the study was performed in the Republican Clinical Hospital, Kazan, Russia.
  
  
  METHODS
  376 patients with RA, 251 healthy first-degree relatives and 227 healthy controls without a family history of autoimmune disease (all females) were examined twice annually over more than 10 years.
  
  
  METHODS
  The following parameters were investigated: type, duration and frequency of infections, bacterial colonisation and serum levels of IgG to bacteria, serum levels of total Ig, plasma cytokine levels, granulocyte reactive oxygen species production, lysozyme activity and phagocytosis.
  
  
  RESULTS
  There were no significant differences in infection rate between healthy controls (median 14 days/year) and RA patients (13). However, infection rates were higher (p<0.001) in healthy relatives (53) and early stage patients (62), which groups also showed heavy bacterial skin colonisation. In contrast, late stage patients had fewer infection days (12; p<0.001) than healthy controls, although bacterial colonisation was still heavy. Phagocyte function and antibacterial antibody generation, together with compensatory cytokine production, were observed to be subnormal in the healthy relatives as well as in RA patients.
  
  
  CONCLUSIONS
  We observed a marked increase in overall infections at the time of RA onset, and signs of a defective antibacterial defence mechanism, contrasting with fewer infections in the late RA stage. It can be speculated that frequent early infections initiate a compensatory immune hyper-reactivity which reduces the infection load while stimulating the development of RA in predisposed individuals.
authors.affiliation: Central Research Laboratory, Kazan State Medical Academy, Kazan, Russia.
authors.forename: Marina I
authors.initials: MI
authors.lastname: Arleevskaya
authors.affiliation: Central Research Laboratory, Kazan State Medical Academy, Kazan, Russia.
authors.forename: Aida G
authors.initials: AG
authors.lastname: Gabdoulkhakova
authors.affiliation: Central Research Laboratory, Kazan State Medical Academy, Kazan, Russia.
authors.forename: Yulia V
authors.initials: YV
authors.lastname: Filina
authors.affiliation: Department of Laboratory Medicine, Lund University, Skane University Hospital, Malmo, Sweden.
authors.forename: Regina R
authors.initials: RR
authors.lastname: Miftakhova
authors.affiliation: Department of Laboratory Medicine, Lund University, Skane University Hospital, Malmo, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Bredberg
authors.affiliation: Department of the Clinical Laboratory Diagnostic, Kazan State Medical Academy, Kazan, Russia.
authors.forename: Anatoly P
authors.initials: AP
authors.lastname: Tsybulkin
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity / Q000235:genetics; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000097:blood / Q000276:immunology*; D011446:Prospective Studies; D012217:Rheumatoid Factor / Q000097:blood / Q000235:genetics / Q000276:immunology*; D012426:Russia / Q000453:epidemiology; D013997:Time Factors
chemical_list: D000907:Antibodies, Bacterial; D001323:Autoantibodies; D016207:Cytokines; D010456:Peptides, Cyclic; D002097:C-Reactive Protein; D012217:Rheumatoid Factor
keywords: IMMUNOLOGY