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Pathogenesis of autoimmune disease

Nature Reviews Nephrology volume 19, pages 509–524 (2023)Cite this article

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Abstract

Autoimmune diseases are a diverse group of conditions characterized by aberrant B cell and T cell reactivity to normal constituents of the host. These diseases occur widely and affect individuals of all ages, especially women. Among these diseases, the most prominent immunological manifestation is the production of autoantibodies, which provide valuable biomarkers for diagnosis, classification and disease activity. Although T cells have a key role in pathogenesis, they are technically more difficult to assay. In general, autoimmune disease results from an interplay between a genetic predisposition and environmental factors. Genetic predisposition to autoimmunity is complex and can involve multiple genes that regulate the function of immune cell populations. Less frequently, autoimmunity can result from single-gene mutations that affect key regulatory pathways. Infection seems to be a common trigger for autoimmune disease, although the microbiota can also influence pathogenesis. As shown in seminal studies, patients may express autoantibodies many years before the appearance of clinical or laboratory signs of disease — a period called pre-clinical autoimmunity. Monitoring autoantibody expression in at-risk populations may therefore enable early detection and the initiation of therapy to prevent or attenuate tissue damage. Autoimmunity may not be static, however, and remission can be achieved by some patients treated with current agents.

Key points

  • Autoimmune diseases lead to diverse patterns of inflammation and organ dysfunction.

  • Autoantibodies are valuable markers for diagnosis, classification and of disease activity.

  • Although T cells play a key part in disease, their assessment is challenging.

  • Autoimmune disease reflects the interplay of genetic and environmental factors.

  • Pre-clinical autoimmune disease provides a window of time for early or preventive treatment.

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Fig. 1: Mechanisms of immune-mediated glomerulonephritis.
Fig. 2: The actions of autoantibodies in immunopathology.
Fig. 3: The stages of autoimmune disease.

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    David S. Pisetsky

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Pisetsky, D.S. Pathogenesis of autoimmune disease. Nat Rev Nephrol 19, 509–524 (2023). https://doi.org/10.1038/s41581-023-00720-1

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