Page 103 - GPD-4-3

Gene & Protein in Disease

SHORT COMMUNICATION
Interferonopathies at the crossroads of

monogenic lupus and autoinflammation: A case
study

1,2
Sulaiman M. Al-Mayouf * and Alhanouf Alsaleem 1
1 Department of Pediatric Rheumatology, King Faisal Specialist Hospital and Research Center,
Riyadh, Saudi Arabia
2 Department of Pediatrics, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

Abstract

Monogenic lupus is a highly complex condition with marked variability, resulting
from diverse immune system etiopathogenesis linked to various pathogenic genetic
variants. There is substantial overlap with newly described systemic autoinflammatory
disorders. We present two cases of monogenic lupus and highlight the intersection
between monogenic lupus and autoinflammatory disorders. This report emphasizes
the concept of monogenic interferonopathies as an umbrella term for various
conditions arising from genetic aberrations in type I interferon (IFN-I) signaling,
which are associated with significant IFN-I activation.

Keywords: Monogenic lupus; Systemic lupus erythematosus; Type I interferon;
*Corresponding author: Interferonopathies
Sulaiman M Al-Mayouf
(mayouf@kfshrc.edu.sa)
Citation: Al-Mayouf SM,
Alsaleem A. Interferonopathies
at the crossroads of monogenic 1. Introduction
lupus and autoinflammation:
A case study. Gene Protein Dis. Systemic sterile inflammatory disorders can be broadly categorized using the semantic
2025;4(3):025080019. immunological concepts of autoimmunity and autoinflammation, each with distinct
doi: 10.36922/GPD025080019 etiopathogenic mechanisms. Autoimmune disorders primarily involve defects in
Received: February 23, 2025 the adaptive immune system, characterized by the presence of autoantibodies and
autoreactive T or B lymphocytes. In contrast, classic autoinflammatory disorders are
Revised: June 5, 2025
linked to aberrations in innate immunity, occurring in the absence of autoantibodies
Accepted: June 16, 2025 and autoreactive lymphocytes, and typically involve the secretion of a single cytokine,
1-3
Published online: July 17, 2025 often due to genetic mutations. Recent advancements in molecular genetics approaches
and immunological diagnostics have revealed a variety of innate immune pathways
Copyright: © 2025 Author(s).
This is an Open-Access article involved in autoinflammatory disorders, including type I interferon (IFN-I), which
distributed under the terms of the plays a crucial role in the pathogenesis of several such conditions. This has expanded the
Creative Commons Attribution spectrum of autoinflammatory disorders, with interferonopathies recently recognized
License, permitting distribution,
4-7
and reproduction in any medium, as a subset. Notably, while autoinflammatory disorders may arise from a single gene
provided the original work is localized in the innate immune system, there is considerable overlap in the pathogenic
properly cited. mechanisms involving the adaptive immune system. This overlap leads to common
Publisher’s Note: AccScience clinical features observed in both monogenic and polygenic disorders, including diverse
Publishing remains neutral with patterns of multiorgan involvement and variable clinical presentations. Systemic lupus
1,3
regard to jurisdictional claims in
published maps and institutional erythematosus (SLE), a prototypical autoimmune disease, is characterized by the loss
affiliations. of self-tolerance, excessive production of pathogenic autoantibodies, and dysregulated

Volume 4 Issue 3 (2025) 1 doi: 10.36922/GPD025080019