The role of NFKB1and NFKBIAin immunoglobulin A vasculitis.

Autores de IDIVAL

• 

  Joao Carlos Batista Liz

  Autor

• María Sebastian Mora-Gil

  Autor

• 

  Rafael Gálvez Sánchez

  Autor

• 

  Luis Martín Penagos

  Autor

• 

  Javier Gonzalo Ocejo Viñals

  Autor

• 

  Ricardo Blanco Alonso

  Autor

• 

  Verónica Pulito Cueto

  Autor

• 

  Raquel López Mejías

  Autor

Autores ajenos al IDIVAL

• Renuncio Garcia, Monica
• Leonardo, Maria Teresa
• Penalba, Ana
• Gabrie, Ligia
• Narvaez, Javier
• Sevilla-Perez, Belen
• Rios Fernandez, Raquel
• Callejas-Rubio, Jose Luis
• Caminal-Montero, Luis
• Collado, Paz
• Perez Venegas, Jose Javier
• Rodriguez Valls, Maria Jose
• De Argila, Diego
• Quiroga Colina, Patricia
• Vicente Rabaneda, Esther Francisca
• Rubio, Esteban
• Leon Luque, Manuel
• Blanco-Madrigal, Juan Maria
• Galindez-Agirregoikoa, Eva

Unidades

• ENFERMEDADES INFECCIOSAS Y MICROBIOLOGIA CLÍNICA

  

  Investigador Responsable

  María Del Carmen Fariñas Álvarez

• INMUNOPATOLOGÍA

  

  Investigador Corresponsable

  Ricardo Blanco Alonso

Abstract

Introduction: Immunoglobulin A vasculitis (IgAV) is an inflammatory disease mediated by B cells. Nuclear factor kappa B (NF-kappaB) is essential for B-cell development and maturation and plays a key role in autoimmunity and inflammation. In particular, the NF-kappaB canonical activation pathway genes NFKB1 (encoding NF-kappaB1) and NFKBIA (encoding NF-kappaB 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-kappaB signaling contributes to IgAV pathogenesis, it likely involves other biological mechanisms. Copyright © 2025 Batista-Liz, Sebastian Mora-Gil, Renuncio Garcia, Leonardo, Penalba, Gabrie, Sanchez, Martin-Penagos, Narvaez, Sevilla-Perez, Rios Fernandez, Callejas-Rubio, Caminal-Montero, Collado, Perez Venegas, Rodriguez Valls, De Argila, Quiroga Colina, Vicente Rabaneda, Rubio, Leon Luque, Blanco-Madrigal, Galindez-Agirregoikoa, Ocejo-Vinyals, Blanco, Pulito-Cueto and Lopez-Mejias.

Keywords

• biomarkers; immunoglobulin A vasculitis (IgAV); NF-kappa B (NF-kB); <italic>NFKB1</italic>; <italic>NFKBIA</italic>