Revisiting B cell tolerance and autoantibodies in seropositive and seronegative autoimmune rheumatic disease (AIRD).
Juliëtte N PouwE F A LeijtenJacob M van LaarM BoesPublished in: Clinical and experimental immunology (2020)
Autoimmune rheumatic diseases (AIRD) are categorized seropositive or seronegative, dependent upon the presence or absence of specific autoreactive antibodies, including rheumatoid factor and anti-citrullinated protein antibodies. Autoantibody-based diagnostics have proved helpful in patient care, not only for diagnosis but also for monitoring of disease activity and prediction of therapy responsiveness. Recent work demonstrates that AIRD patients develop autoantibodies beyond those contained in the original categorization. In this study we discuss key mechanisms that underlie autoantibody development in AIRD: defects in early B cell development, genetic variants involved in regulating B cell and T cell tolerance, environmental triggers and antigen modification. We describe how autoantibodies can directly contribute to AIRD pathogenesis through innate and adaptive immune mechanisms, eventually culminating in systemic inflammation and localized tissue damage. We conclude by discussing recent insights that suggest distinct AIRD have incorrectly been denominated seronegative.
Keyphrases
- systemic lupus erythematosus
- disease activity
- rheumatoid arthritis
- rheumatoid arthritis patients
- end stage renal disease
- multiple sclerosis
- ankylosing spondylitis
- chronic kidney disease
- ejection fraction
- prognostic factors
- newly diagnosed
- juvenile idiopathic arthritis
- peritoneal dialysis
- patient reported outcomes
- stem cells
- risk assessment
- oxidative stress
- small molecule
- mesenchymal stem cells
- binding protein
- drug induced
- protein protein
- bone marrow
- smoking cessation
- replacement therapy