Preclinical Systemic Lupus Erythematosus

Despite the exceptional progress in breast cancer pathogenesis, prognosis, diagnosis, and treatment strategies, it remains a prominent cause of female mortality worldwide. Additionally, although chemotherapies are effective, they are associated with critical limitations, most notably their lack of specificity resulting in systemic toxicity and the eventual development of multi-drug resistance (MDR) cancer cells. Liposomes have proven to be an invaluable drug delivery system but of the multitudes of liposomal systems developed every year only a few have been approved for clinical use, none of which employ active targeting. In this review, we summarize the most recent strategies in development for actively targeted liposomal drug delivery systems for surface, transmembrane and internal cell receptors, enzymes, direct cell targeting and dual-targeting of breast cancer and breast cancer-associated cells, e.g., cancer stem cells, cells associated with the tumor microenvironment, etc.

Laboratory tests are indeed helpful in the diagnosis and follow-up of rheumatic diseases. Alterations in laboratory parameters have been included among the classification or diagnostic criteria of several rheumatologic conditions and used as a means of monitoring disease activity and response to therapies. Apart from acute-phase reactants, which are unselectively increased across many inflammatory disorders, other laboratory findings may work as specific disease biomarkers, having therefore a diagnostic and prognostic role in clinical practice. Nevertheless, the request of laboratory tests should be dictated by a clear clinical indication in order to avoid misinterpretation and misdiagnosis.

The aim of this chapter is to provide a comprehensive guidance on the indications, interpretation, and pitfalls of the laboratory tests currently available for the most relevant rheumatic diseases.

In this chapter, we will discuss the challenges in systemic lupus erythematosus (SLE), covering the preclinical as well as clinical perspectives. These will include (1) areas where further insight into the pathogenesis of SLE is in need: (i) genetic predisposition such as SLE risk genes, type I interferonopathies and C1q deficiency; (ii) immunological disturbances such as defects in apoptosis and cytokine networks, neutrophil extracellular traps (NETs) formation, and aberrant activation of immune cells and autoantibody production; (iii) epigenetic changes caused by environmental factors such as ultraviolet radiation, occupational exposures, infectious agents as well as drug exposure. (2) issues in the classification systems, validation process, and diagnosis of SLE high on future research agenda; (3) different autoantibody profiles and particular clinical phenotypes in terms of diagnostic and prognostic values; and (4) three major unmet needs in the management of patients with SLE: (i) management of cardiovascular disease risk, (ii) management of LN, and (iii) management of refractory SLE, focusing on phase 2 and 3 novel biological drugs targeting at B cells, interferon signaling, and plasmacytoid dendritic cells. Regardless of various challenges in understanding pathogenic pathways, precise identification of phenotypes, and the advancement of targeted treatments with improved efficacy and safety, the ultimate treatment goal is to achieve remission and low disease activity in each patient with SLE.

Despite evidence from human and animal studies of pesticide immunotoxicity, little is known about the relationship between agricultural pesticide use and autoimmunity. The objective of the present study was to assess the association between pesticide use and anti-cyclic citrullinated peptide (anti-CCP) antibodies and antinuclear antibodies (ANA) levels. A cross-sectional study including healthy 52 agricultural and 68 non-agricultural workers aged 17–69 years was conducted in the Rio de Janeiro State, Brazil. Serum samples were tested for anti-CCP and ANA by ELISA. Data on pesticide use and covariates were obtained through structured questionnaires. We estimated associations of pesticides and other exposures with log-transformed antibody levels, adjusted for sex, age, education, crops, and fertilizers by multiple linear regression analyzes. Anti-CCP levels were associated with growing certain crops, agricultural tasks, and the use of mancozeb, paraquat, and methomyl. ANA levels were positively associated with azoxystrobin and inversely associated with linuron. These novel findings suggest associations of specific pesticides and fertilizers with anti-CCP antibodies in this healthy agricultural population, supporting the need for larger human studies of preclinical autoimmunity and pesticides.

The complement system has been intimately linked to systemic lupus erythematosus (SLE). Until recently, this association was viewed as inexplicably paradoxical. On the one hand, complement activation is thought to mediate tissue inflammation and contribute significantly to organ damage in patients with SLE. On the other hand, hereditary deficiencies of early components of the complement classical pathway impose a strikingly high risk for developing SLE. With an accelerated pace of advances over the past decade, the perplexing relationship of complement with SLE is being unraveled. This chapter will review the biology of the complement system in relation to SLE, focusing on the novel findings made in the past decade, revisit the utility of complement as biomarkers for SLE, and consider the potential of anticomplement therapeutics in SLE.