159. INFECTIONS ARE ASSOCIATED WITH INCREASED RISK OF MPO- BUT NOT PR3-ANCA-ASSOCIATED VASCULITIS - A POPULATION-BASED CASE-CONTROL STUDY FROM SOUTHERN SWEDEN

Abstract

Background: Previous studies have implicated infection as a contributing factor in the pathogenesis of ANCA associated vasculitis (AAV). Host response to microbials can lead to loss of tolerance and production of anti-neutrophil cytoplasmic antibodies (ANCA). ANCA are important in the development of AAV. This study examines the occurrence of infections and later development of MPO- or PR3-ANCA associated vasculitis. Method(s): All incident cases of AAV in the geographical area of Skane (Pop.0.75mio) in Southern Sweden, diagnosed between 2000 and 2016 were included. For each AAV case, 10 randomly selected controls from the background populations were matched for age, sex and area of residence. Date of AAV diagnosis in patients was defined as index date in respective controls. Using the ICD-10 codes, all infection events before the date of AAV diagnosis (and index date for controls) were identified using a centralized database, the Skane healthcare register. Infections occurring within <6 months prior to AAV diagnosis (or index-date) were excluded to reduce the risk for incorrect classification as an AAV manifestation. Conditional logistic regression models were used to calculate odds ratio (OR) and 95% confidence intervals (CI). Patients were stratified according to their ANCA serotype (PR3- and MPO-ANCA). Result(s): 273 patients with AAV (131 women, 48%) and 2717 controls were included in this study. In total 138 (50.5%) unique infections were assigned for AAV prior to the date of AAV diagnosis vs 1266 (46.6) for controls. Upper respiratory tract infections (URTI) and pneumonia (PN) were more common among patients going to develop AAV vs. controls (URI: 21.2% vs. 16.8%, PN: 8.1% vs 5.3) yielding an OR of 1.42 (95% CI 1.01-2.01) for URTI and 1.70 (95% CI 1.02-2.82) for PN (Table 1). The differences were only significant for patients with MPO-ANCA and not PR3-ANCA associated diseases. The median time from the infection nearest onset of AAV was 37.9 months (IQR 11.9-51.9) in patients, whereas the corresponding median time for the controls 46.1 months (IQR 16.5-63.9). Conclusion(s): Upper respiratory tract infections, ENT infections as well as pneumonias and influenza were associated with later development of MPO-ANCA positive vasculitis but not PR3-ANCA vasculitis. The differences in the genetic characteristics of MPO- and PR3-ANCA associated diseases might affect the consequences of triggering the immune system by different microorganisms. URTI: Upper respiratory tract infections, LRTI: lower respiratory infections, ENT: ear-nose and throat, UTI: urinary tract infection.