WP 1. Predictors of rheumatic disease in healthy individuals

This area of work will be led by Partner 12 (Umeå) with input from Partner 1 (Stockholm), Partner 4 (Vienna), Partner 6 (Amsterdam), 8 (Nijmegen), 14 (Manchester), 21 (EULAR), and Partner 25 (BMD)

During the first 18 months, analyses will be carried out on samples from individuals identified in the Northern Sweden Health and Disease Study (NSHDS) cohort (which comprises donations of biological specimens from population-based surveys) and the Maternity cohort of Northern Sweden . In total, the biobank from the NSHDS cohort comprises 122,800 samples from 79,940 individuals; 34,375 males and 45,565 females. The Maternity cohort (78,700 women with 102,800 samples) comprises pregnant women screened for rubella since 1976 from the four northernmost counties in Sweden (population about 900,000). Individuals in Sweden are identified by a unique identification number available at a national level which enables us to track individuals in different registers such as disease registers, blood bank registers and maternity registers.

•  Women and men with early RA will be identified from a disease register of early arthritis in Northern Sweden by Partner 12 (Umeå). Their identification number will be matched to the Northern Sweden Health and Disease Study (NSHDS) cohort and the Maternity cohort of Northern Sweden to identify blood samples donated before disease onset.

•  Controls matched for sex, age and ethnicity will be identified for each patient from the NSHDS biobank.

•  By means of a nested case-control approach, cases with arthritis and controls are selected and sera/plasma from before disease onset will be identified within the blood bank, aliquoted and analysed for presence of several autoantibodies (see WP 13 on autoantibodies and proteomics).

•  DNA from patients and controls DNA will be collected and extracted.

•  Candidate genes identified from other parts of the project (see above and WP 11) will be tested.

•  A questionnaire to identify environmental factors will be constructed, distributed and collected to the identified patients and controls.

•  Analyses will be started of genetic associations to clinical phenotypes and presence of antibody profiles etc. as phenotype.

•  Certain antibody patterns and certain genetic contexts as well as environmental risk factors to develop RA will be defined.

After the first 18 months the next step will be to extend the same approach as outlined above to a larger population in Sweden and the UK .