Clinical, Epidemiological and Immunological Aspects of Lyme Borreliosis with Special Focus on the Role of the Complement System

............................................................................................................................. 9 SAMMANFATTNING PÅ SVENSKA ................................................................................ 11 LIST OF PAPERS.................................................................................................................. 13 ABBREVIATIONS ................................................................................................................ 15 INTRODUCTION.................................................................................................................. 19 Borrelia burgdorferi sensu lato............................................................................................ 19 Ecology................................................................................................................................. 22 Epidemiology ....................................................................................................................... 23 Clinical disease..................................................................................................................... 24 Dermatoborreliosis ........................................................................................................... 25 Neuroborreliosis ............................................................................................................... 26 Arthritis ............................................................................................................................ 27 Rare manifestations .......................................................................................................... 27 Asymptomatic seroconversion ......................................................................................... 28 Laboratory diagnosis ............................................................................................................ 28 Direct detection methods.................................................................................................. 28 Indirect detection methods ............................................................................................... 30 Therapy................................................................................................................................. 32 Prognosis .............................................................................................................................. 34 Immunity to infection........................................................................................................... 35 The innate immune response............................................................................................ 37 The adaptive immune response ........................................................................................ 42 Cytokines and chemokines............................................................................................... 43 T helper cell subsets ......................................................................................................... 44 Immunology of Lyme borreliosis..................................................................................... 45 AIMS ....................................................................................................................................... 49 MATERIALS AND METHODS........................................................................................... 51 Subjects ................................................................................................................................ 51 Case definitions ................................................................................................................ 51 Patients and controls......................................................................................................... 51 Excluded subjects............................................................................................................. 53 Methods................................................................................................................................ 55 Data collection.................................................................................................................. 55 Borrelia serology.............................................................................................................. 55