An Animal Model Using Metallic Ions to Produce Autoimmune Nephritis

Abstract

Autoimmune nephritis triggered by metallic ions was assessed in a Long-Evans rat model. The parameters evaluated included antinuclear autoantibody production, kidney damage mediated by immune complexes detected by immunofluorescence, and renal function tested by retention of nitrogen waste products and proteinuria. To accomplish our goal, the animals were treated with the following ionic metals: HgCl2, CuSO4, AgNO3, and Pb(NO3)2. A group without ionic metals was used as the control. The results of the present investigation demonstrated that metallic ions triggered antinuclear antibody production in 60% of animals, some of them with anti-DNA specificity. Furthermore, all animals treated with heavy metals developed toxic glomerulonephritis with immune complex deposition along the mesangium and membranes. These phenomena were accompanied by proteinuria and increased concentrations of urea. Based on these results, we conclude that metallic ions may induce experimental autoimmune nephritis.

Urinary Metals Concentrations and Biomarkers of Autoimmunity among Navajo and Nicaraguan Men

“…Although, other metals were also positively associated with ANA, the associations were weak or close to null. Lead was the only metal examined in our study with toxicological literature supporting the association [19,69]. However, a recent epidemiological analysis by Dinse et al [16] found no association between blood lead in NHANES and ANA among men and women, a result which is inconsistent with those of the present study.…”

Patients affected by a new variant of endemic pemphigus foliaceus have autoantibodies colocalizing with MYZAP, p0071, desmoplakins 1-2 and ARVCF, causing renal damage

“…We previously showed the presence of mercuric sulfides/selenides and other undetermined materials in skin biopsies of patients with EPF using autometallography and electron microscopy analysis . It has previously been demonstrated that ionic metals including HgCl 2 and CuSO 4 may cause kidney damage mediated by immune complexes in Long–Evans rats …”

Associated Autoimmunity and Lead Exposure in Childhood

“…The autoimmunity associated with environmental pollutants such as heavy metals is a phenomenon that has been studied widely, and a strong body of epidemiological and experimental evidence suggests that exposure to mercury, lead, and other metals could be associated with the development of autoimmunity. Animal models and in vitro studies have contributed to a better understanding of the molecular mechanisms by which metallic pollutants can induce immune dysregulation [2].…”

“…Additionally, metallic pollutants such as lead may affect the hydrophobic centres of proteins or may disrupt disulfide bridges or salt bridges and modify secondary or tertiary structures. The effect of metals on proteins can be predicted by determining the sites of adhesion dependent on metal ions or MIDAS [2]. In sum, conformational changes in a protein could increase its antigenicity, favouring immunologic tolerance breakdown.…”

“…The effects on the immune system may result from the interaction between metal ions and normal proteins, which induce conformational changes in the proteins and trigger self-immune responses and/or cell hypersensitivity. Another way in which metals can stimulate the immune system is by inducing apoptosis and/or necrosis of the exposed tissues, with the consequent externalization of apoptotic remains, which may trigger an autoimmune response [1][2][3][4].…”