Proof-of-concept evidence for lncRNA NRIR downregulation in antiphospholipid syndrome and its obstetric subtype

Carlos A. Guzmán-Martín, Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Coyoacán; 2Departamento de Fisiología, Instituto Nacional de Cardiología Ignacio Chávez, Tlalpan; Mexico City, Mexico
Yaneli Juárez-Vicuña, Departamento de Inmunología, Instituto Nacional de Cardiología Ignacio Chávez, Tlalpan, Mexico City, Mexico
Laura A. Martínez-Martínez, Departamento de Reumatología, Instituto Nacional de Cardiología Ignacio Chávez, Tlalpan, Mexico City, Mexico
Fausto Sánchez-Muñoz, Departamento de Fisiología, Instituto Nacional de Cardiología Ignacio Chávez, Tlalpan, Mexico City, Mexico
Rodrigo Romero-Nava, Laboratorio de Investigación en Genética de Enfermedades Metabólicas, Escuela Superior de Medicina, Instituto Politécnico Nacional, Miguel Hidalgo. Mexico City, Mexico

Background/Objetive: Long non-coding RNAs (lncRNAs) regulate immune signaling pathways, including interferon (IFN)-mediated responses implicated in antiphospholipid syndrome (APS). The IFN-inducible lncRNA NRIR (AC017076.5) exhibits context-dependent regulatory functions and has been associated with modulation of STAT1/STAT2 activation in human monocytes. Its expression profile in APS remains unexplored. Method: In this cross-sectional exploratory study, NRIR expression was quantified by reverse transcription–quantitative PCR in CD14-enriched peripheral blood monocytes from APS patients and age- and sex-matched healthy controls. Relative expression was calculated using the 2–ΔΔCt method with GAPDH as endogenous control. Subgroup analyses compared obstetric APS (OAPS) and non-obstetric APS (NOAPS). Complementary in silico protein–protein interaction and pathway enrichment analyses contextualized NRIR within IFN-related networks. Results: NRIR expression was significantly reduced in APS compared with controls. OAPS patients exhibited less pronounced downregulation than NOAPS, showing an intermediate expression pattern. Network analysis identified a STAT1-centered IFN-enriched module related to antiviral and type I IFN signaling, with NRIR positioned peripherally. Functional inferences remain hypothesis-generating due to sample size and absence of direct IFN measurements. Conclusion: NRIR is downregulated in peripheral monocytes from APS patients, with phenotype-dependent differences. Further mechanistic and IFN-integrated studies are required.

Keywords: Antiphospholipid syndrome. Obstetric APS. NRIR. lncRNA AC017076.5. Interferon response. Monocytes.