Year: 2025
Type: article
Study design: Observational Study
Abstract: Introduction Immunoglobulin A vasculitis (IgAV) is an inflammatory disease mediated by B cells. Nuclear factor kappa B (NF-κB) is essential for B-cell development and maturation and plays a key role in autoimmunity and inflammation. In particular, the NF-κB canonical activation pathway genes NFKB1 (encoding NF-κB1) and NFKBIA (encoding NF-κB inhibitor alpha) have been identified as risk loci for several immune-mediated diseases, but their role in IgAV remains unclear. This study aimed to determine whether NFKB1 and NFKBIA represent novel genetic risk factors for IgAV pathogenesis. Methods The NFKB1 promoter variant −94 ins/del ATTG (rs28362491), six tag NFKB1 polymorphisms (rs77830930, rs1598856, rs7340881, rs4648055, rs4648090, and rs230547), and seven tag NFKBIA variants (rs3138055, rs696, rs1022714, rs2233419, rs2233415, rs1050851, and rs1957106) were genotyped in 343 Caucasian IgAV patients and 764 healthy, ethnically matched controls using TaqMan probes. Patients were stratified according to age at disease onset and the presence or absence of renal, articular, and gastrointestinal manifestations. Genotype, allele, and haplotype frequencies were compared between patients and controls, as well as across clinical subgroups. Results No statistically significant differences were found in genotype or allele frequencies of NFKB1 or NFKBIA between IgAV patients and healthy controls. Likewise, haplotype frequencies of both genes were similar across groups. No associations were observed when patients were stratified by clinical features, including renal involvement, age at onset, or articular/gastrointestinal symptoms. Conclusion Our findings do not support a major role for the NFKB1 or NFKBIA variants studied in IgAV susceptibility or severity. These results suggest that if NF-κB signaling contributes to IgAV pathogenesis, it likely involves other biological mechanisms.
Source: Frontiers in Immunology
Authors: Joao Carlos Batista-Liz, María Sebastián Mora-Gil, Mónica Renuncio García, María Teresa Leonardo, Ana Peñalba, Ligia Gabrie, Rafael Gálvez Sánchez, Luis Martín-Penagos, Javier Narvaez, Belén Sevilla-Pérez, Raquel Ríos Fernández, José Luis Callejas-Rubio, Luis Caminal-Montero, Paz Collado, José Javier Pérez Venegas, María José Rodríguez Valls, Diego De Árgila, Patricia Quiroga Colina, Esther Francisca Vicente Rabaneda, Esteban Rubio, Manuel León Luque, Juan María Blanco-Madrigal, Eva Galíndez-Agirregoikoa, Javier Gonzalo Ocejo-Vinyals, Ricardo Blanco, Verónica Pulito-Cueto, Raquel López-Mejías
Institutions: Instituto de Investigación Marqués de Valdecilla, Complejo Asistencial Universitario de León, Marqués de Valdecilla University Hospital, Bellvitge University Hospital, Instituto de Investigación Biosanitaria de Granada, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias, Hospital Universitario Severo Ochoa, Hospital Universitario de Jerez, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa, Universidad Autónoma de Madrid, Hospital Universitario Virgen del Rocío, Hospital de Basurto
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
Awards: G1244119120, G1963671815, G3438357353, G4054636021, Caracterización de las bases moleculares de la vasculitis mediada por IgA mediante secuenciación del transcriptoma de célula única de linfocitos B circulantes, G577017494, G679669155, Perfil epigenómico de la vasculitis IgA: primer estudio de accesibilidad de la cromatina en todo el genoma a nivel de célula única de linfocitos B circulantes, G7562821947
OpenAlex ID: W4415494765