Reumatologia: pesquisas atuais
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Building Rational Models of Humoral Autoimmunity: The Example of Lupus Tubulointerstitial Nephritis

Andrew J Kinloch

Mice have proven to be extremely useful tools for simulating pathways involved in humoral autoimmune diseases observed in patients. A relevant animal model can act as a means with which existing drugs can be tested and new ones rationally designed. With a view to rationally developing animal models, the common features of organ-specific autoantibody-mediated diseases are briefly recalled herein. Historically however, hurdles have often existed that have thwarted the description of these features, and therefore the development and testing of hypotheses that explain pathways that yield autoimmune pathologies. The difficulties in assembling these hypotheses from human data have included acquisition of sufficient information regarding antibodies, antigens and genetics, and the subsequent marrying of these data-sets with particular clinical manifestations. Moreover, once well-assembled hypotheses have been generated, appropriate platforms for their testing are frequently absent. In the mouse, the immunologists’ ‘go-to’ simulation platform, components integral to mounting antigen specific immune responses are often poorly conserved, or even absent. In this review, following a description of some of the cross species inconsistencies, tools such as plasmids for expressing murine monoclonal antibodies with human variable regions, and mice engineered to express human Fcγ receptors, and HLA molecules, often capable of surmounting these issues, are highlighted. By avoiding historical pitfalls, and considering how new technologies could be employed in the future, a rational approach will be devised for the detailed characterization of the recently discovered organ-specific autoimmune phenomenon lupus Tubulointerstitial Nephritis (TIN), and an animal model that simulates it.