Pathogenesis and prevention of rheumatic disease: focus on preclinical RA and SLE

Abstract

Established and emerging data demonstrate that a ‘preclinical’ period of disease precedes the onset of clinical rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), as well as other autoimmune rheumatic diseases (ARDs).This preclinical stage of development of disease is characterized by abnormalities in disease-related biomarkers before the onset of the clinically apparent signs and symptoms. Numerous genetic and environmental risk factors for ARDs have also been identified, and many of these factors are likely to act before the clinical appearance of tissue injury to initiate and/or propagate autoimmunity and autoimmune disease. Thus, biomarkers representative of these autoimmune processes could potentially be used in conjunction with other clinical parameters during the preclinical period of ARDs to predict the future development of clinically apparent disease. This Review focuses on the preclinical stages of RA and SLE, as our current understanding of these diseases can be used to present an overall model of the development of ARDs that might ultimately be used to develop screening programmes and preventive strategies. Important considerations for the future development of such approaches, in particular, the issues that require additional research and how they might be addressed, are also discussed.

Early, Incomplete, or Preclinical Autoimmune Systemic Rheumatic Diseases and Pregnancy Outcome

“…Systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SS), undifferentiated connective tissue disease (UCTD), and other systemic autoimmune diseases are chronic diseases that progress over the years and are preceded by a long period of time with detectable autoantibodies and few symptoms (2)(3). The final diagnosis of these diseases requires the presence of several signs and symptoms according to internationally validated classifications (4).…”

“…The major systemic autoimmune rheumatic diseases, including RA, SLE, Sjögren's syndrome, and other connective tissue diseases are relatively common, with a 5% prevalence in the general population and a lifetime risk of 8.4% among women (34). However, the natural history of these disorders follows a pattern of progression lasting several years from a preclinical non-diagnostic phase to an overt disease (2,3). Thus, the prevalence of 2.9% (150/5232) of preclinical or transient autoimmune disorders among young women recruited into our study was not surprising.…”

Childhood Residential and Agricultural Pesticide Exposures in Relation to Adult-Onset Rheumatoid Arthritis in Women

“…In the current study, the questionnaire referred only to "insecticides or pesticides …used to treat insects, rodents, or other pests." Mechanisms leading to the development of RA are not fully understood but are thought to involve immune dysregulation leading to production of specific autoantibodies and increased inflammatory cytokines, the convergence of which results in clinical symptoms and damage (31). Although no experimental models of RA have been used to study the role of pesticide exposure, general toxicology studies suggest a diverse range of immunological effects through which earlylife pesticide exposures may contribute to later-life immune dysregulation and inflammation in RA (32,33).…”

New laboratory markers for the management of rheumatoid arthritis patients

“…Genetic factors are, however, also implicated in the susceptibility and the evolution of RA. A genetic association with antigens of the major hystocompatibility complex (MHC)-II, and in particular human leukocytes antigens (HLA)-DRB1, has been well established, although non-HLA associated loci have also been linked to the disease [10,11]. Although the cause of RA is still unknown, autoimmunity plays an important role.…”