Protection against lupus-like inflammatory disease is in the LAP of non-canonical autophagy

Thomas. Scambler, Conor Feeley, Michael F. McDermott


Immunological diseases have been proposed to exist as a continuum, with innate immune-mediated autoinflammatory disease at one end of the spectrum and adaptive immune-mediated autoimmune disease at the other (1). Systemic lupus erythematosus (SLE) is often described as the quintessential autoimmune disease, with disease manifestations existing in multiple tissues throughout the body, particularly the skin, kidneys and brain. Phenotype variability among individual sufferers, as well as differences in disease severity also lead to specific diagnostic and therapeutic dilemmas. Symptoms associated with SLE include fever, chest pain, swollen lymph nodes, a red rash most commonly found on the face, as well as painful Raynaud’s phenomenon and swollen joints, with many patients also developing arthritis. This diversity in clinical features is due to a loss of control of self-tolerance of both the innate and adaptive immune systems (2). This array of clinical features is mirrored by the complexity of the many factors which may cause the disease, including genetic, environmental and hormonal. It is widely postulated that the root cause of SLE may involve an unknown environmental agent, triggering one’s existing genetic susceptibility and underlying immune system defects, with vitamin D deficiency as one such example (3). One certainty is that the adaptive immune response orchestrates the vast majority of SLE manifestations, by the presence of activated autoimmune T- and B- lymphocytes. However, the root cause of the disease remains elusive, and a diagnosis of SLE is typically confirmed once an individual is experiencing at least four of the eleven common signs of the disease (4,5). Of these eleven, a positive test for antinuclear antibody (ANA) is typically the most shared feature among patients.