Monogenic autoimmune and autoinflammatory disorders in adulthood: recent discoveries and implications for rheumatology practice

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ID: 317071
2026
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Abstract
Advances in high-throughput sequencing and genotype-first approaches have revealed a growing number of monogenic autoimmune and autoinflammatory conditions that present in late adolescence or adulthood and sometimes mimic more common rheumatologic diseases. These disorders arise from both germline and somatic mutations and span a broad spectrum of immune dysregulation, including autoinflammation, autoimmunity, immunodeficiency, allergic disease, and hematological disorders. Importantly, many affected individuals do not exhibit classical Mendelian inheritance or early-onset disease, instead presenting with incomplete penetrance, variable expressivity, or atypical phenotypes that fulfill established classification criteria for diseases such as systemic lupus erythematosus and vasculitides. In this review, we highlight recently described monogenic immune disorders with relevance to adult rheumatology practice, including germline inborn errors of immunity and somatic mutation-driven conditions. We discuss emerging mechanisms that link innate and adaptive immune dysregulation, clinical features that should prompt genetic evaluation, and practical considerations for genetic testing in adult patients. Finally, we examine current challenges and future opportunities in integrating molecular diagnostics into rheumatology care, emphasizing the potential for genetic diagnoses to refine disease classification and inform targeted, mechanism-based therapeutic approaches.
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openalex_W7164387268 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Jason Evan Liebowitz, Reid Weisberg, Yiyun Shi, Yiming Luo
Journal Lara D. Veeken
Year 2026
DOI
10.1093/rheumatology/keag299
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