The position of geochemical variables as causal co-factors of diseases of unknown aetiology

ABSTRACT: The term diseases of unknown aetiology (DUA) or idiopathic diseases is used to describe diseases that are of uncertain or unknown cause or origin. Among plausible geoenvironmental co-factors in causation of DUA, this article focusses on the entry of trace elements, including metals and metalloids into humans, and their involvement in humoral and cellular immune responses, representing potentially toxic agents with implications as co-factors for certain DUA. Several trace elements/metals/metalloids (micronutrients) play vital roles as co-factors for essential enzymes and antioxidant molecules, thus, conferring protection against disease. However, inborn errors of trace element/metal/metalloid metabolisms can occur to produce toxicity, such as when there are basic defects in the element transport mechanism. Ultimately, it is the amount of trace element, metal or metalloid that is taken up, its mode of accumulation in human tissues, and related geomedical attributes such as the chemical form and bioavailability that decisively determine whether the exerted effects are toxic or beneficial. Several case descriptions of DUA that are common worldwide are given to illustrate our knowledge so far of how trace element/metal/metalloid interactions in the immune system may engender its dysregulation and be implicated as causal co-factors of DUA. ARTICLE HIGHLIGHTS: The importance of a proper understanding of geochemical perturbations in human metabolisms is emphasised. It is proferred that such an understanding would aid greatly in the decipherment of diseases of unknown aetiology (DUA). The thesis presented may pave the way towards better diagnosis and therapy of DUA.