TITLE:
Cutaneous Lupus Erythematosus as a Proposed Sentinel Model of Systemic Autoimmunity: Immunobiological Convergence between the Skin and Systemic Disease
AUTHORS:
Gustavo Alberto Gutiérrez-Barros, María Victoria Morales-Morales, Gabriela María Morales-Donado, Sharon Nicole Rueda-Cogollo, Daniela Valentina Fontalvo-Bustamante, Isabella María Mercado Athias, Katheryn Coronel Ortiz, Jafet David Rios Pérez, Eva Esther Hinestrosa Flórez, Edilma Rosa Quintero Gámez, Eliannys Paola Quintero Gámez, Ricardo José Boneth Pérez, Jair Jose Daza Redondo, Leonel David Mendoza Daza, Valery Paola Jiménez López
KEYWORDS:
Cutaneous Lupus Erythematosus, Sentinel Organ, Type I Interferon
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.14 No.5,
May
22,
2026
ABSTRACT: Cutaneous lupus erythematosus (CLE) has traditionally been considered a dermatologic manifestation within the lupus spectrum; however, recent clinical, immunologic, and transcriptomic evidence suggests that the skin may constitute an immunologically active and accessible compartment for studying early stages of lupus autoimmunity. In this review, the concept of a “sentinel model” is used as a proposed integrative hypothesis, and not as an established pathogenic mechanism or as evidence that the skin is the demonstrated causal origin of systemic disease. We synthesize the available evidence on local cutaneous immune activation, highlighting the role of the keratinocyte as an immunologically active cell capable of producing type I interferons, particularly interferon-kappa (IFN-κ), and of participating in nucleic acid-sensing pathways such as cGAS-STING. These mechanisms support the existence of an interferon-dominated cutaneous inflammatory signature; nevertheless, their direct contribution to systemic propagation remains incompletely defined. Additionally, transcriptomic studies have identified shared inflammatory programs between the skin and target organs such as the kidney in lupus nephritis, especially those related to interferon-stimulated genes, chemokines, and infiltrating immune populations. These similarities support immunobiological convergence between tissue compartments, but do not by themselves demonstrate direct cellular migration or skin-organ causality. Finally, we discuss the role of phenotypic, serologic, and molecular stratification in identifying patients with CLE at risk of systemic progression. Hydroxychloroquine retains an established role in cutaneous disease control, whereas its potential disease-modifying effect on progression to systemic lupus erythematosus should be interpreted as emerging and non-definitive evidence. Similarly, therapies targeting the interferon pathway have shown benefit in populations with established SLE and cutaneous involvement, but their ability to prevent systemic progression in isolated CLE has not yet been demonstrated.