An etiopathogenesis of juvenile idiopathic arthritis: the protein-homeostasis-system hypothesis.

The initiation of juvenile idiopathic arthritis (JIA) may be associated with an infection caused by unidentified pathogens. The prevalence or incidence rates of JIA differ markedly among populations. The constituent of microbiota of human species is influenced by age during childhood and differs among ethnic groups. On occasion, some strains in microbiota can invade the host and elicit inflammatory immune reactions, and dysbiosis has been observed in JIA. The microbial-infected cells contain inflammation-inducing substances including pathogen-origin substances such as toxins and pathogen-associated molecular patterns and host cell-origin substances such as damage-associated molecular patterns, biochemicals, and pathogenic proteins/peptides. The immune systems of mammals, especially adaptive immune system, mature along with ages in childhood and decline in old age. JIA has epidemiological and clinical characteristics including different incidence by ethnic groups with similar age and sex predilection in certain subtypes, an association with various infectious and immune-mediated diseases and physical trauma, and a different clinical nature as compared with arthritis in adults. Here, it is proposed that causal agents of JIA are certain strains in microbiota, and etiological or inflammation-inducing substances in JIA are derived from the infected or injured cells through the characteristics of JIA and the PHS hypothesis. Patients with JIA may have an immature or improper adaptive immune state for controlling of the substances.