Rheumatoid Arthritis - Pathogenesis Flashcards
Function of synovium
Maintain intact tissue surface Lubricate cartilage Control synovial fluid volume Control synovial fluid composition - hyaluronan, lubicin Nutrition of chondrocytes
RA is a chronic, symmetric and polyarticular inflammatory joint disease. What are 3 features of rheumatoid synovitis?
Inflammatory cell infiltration
Synoviocyte proliferation
Neoangiogenesis
What cells are found in the synovial fluid of a rheumatoid joint?
Neutrophils
What is pannus?
An abnormal layer of fibrovascular or granulation tissue that forms over the articular surface
Causes bone and cartilage destruction leading to joint deformity
Which antibodies are associated with rheumatoid arthritis?
Rheumatoid Factor
Anticitrullinated protein
Autoantibodies to type II collagen and systemic antigens eg glucose phosphate isomerase
What process is activated by autoimmune responses in RA?
Complement
Leads to inflammation
Seropositive RA patients have which antibodies?
Rheumatoid Factor
Anticitrullinated Protein Antibodies ACPA
How is seropositive RA diagnosed?
Anti-CCP assays recognise self citrullinated proteins
Which proteins will be recognised to be self citrullinated in anti CCP diagnostic assays?
Keratin, fibrinogen, alpha enolose, fibronectin, collagen, vimentin
How does prognosis for patients compare between seropositive and seronegative cases of RA?
Seropositive have a less favourable prognosis
Which genetic polymorphism is associated with RA?
HLA DRB1 - promotes autoimmunity
Others -PTPN22, CTLA4, c-rel
What environmental factors may contribute to RA?
Smoking
Bronchial stress
Infection
Which infectious agents are associated with Rheumatoid arthritis?
Viruses E.coli Mycoplasma Periodontal disease - Porphyromonas gingivalis Gut microbes of the microbiome
3 events in pathogenesis of RA leading to ACPA response
Repeated insults in genetically susceptible individual
Formation of immune complexes and rheumatoid factor
Alteration in citrullination of proteins and breakdown of tolerance
What is citrullination?
Conversion of arginine to citrulline