AB1240 NLRP3 AND CASP1 GENES AS DISCRIMINATORY MARKERS BETWEEN IGA VASCULITIS AND IGA NEPHROPATHY?
Authors: J. C. Batista-Liz, M. Sebastián Mora-Gil, L. Gabrie, R. Gálvez-Sánchez, M. T. Leonardo, A. Peñalba, B. Sevilla-Pérez, J. L. Callejas, L. Caminal-Montero, J. Narváez, L. Martín-Penagos, L. Belmar-Vega, P. Collado, A. Fernández-Nebro, G. Díaz-Cordoves, P. Quiroga Colina, E. Vicente-Rabaneda, S. Cigarrán, J. Calviño, C. Cobelo, E. Rubio-Romero, M. León Luque, J. M. Blanco-Madrigal, E. Galíndez-Agirregoikoa, S. Castañeda, R. Blanco, V. Pulito-Cueto, R. López-Mejías
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Immunoglobulin A Vasculitis (IgAV) is an inflammatory disease caused by the accumulation of immune complexes of IgA in the walls of small blood vessels of skin, joints, gut, and kidney [1,2]. Likewise, Immunoglobulin A Nephropathy (IgAN) is characterized by the deposition of IgA immune complexes, although IgAN is limited to the kidney. Interestingly, the nephritis caused by IgAV (IgAVN) is indistinguishable from IgAN. One factor that many nephropathies share, including IgAN, is the activation of the NLR family pyrin domain-containing 3 (NLRP3) protein, one of the best-understood members of the inflammasome [3]. NLRP3 is also known for activating Caspase 1, an enzyme that cleaves inflammatory precursors involved in several nephropathies, and its levels have been linked to acute kidney injury and the pathogenesis of IgAV [4,5]. Accordingly, it is plausible to consider that these molecules could play a role in the discrimination of these diseases. <h3>Objectives:</h3> The aim of this work was to assess whether <i>NLRP3</i> and <i>CASP1</i> could be considered as genetic biomarkers for the differential diagnosis of IgAV and IgAN. <h3>Methods:</h3> 342 patients with IgAV (of which 116 developed IgAVN), the largest series of Caucasian patients with IgAV ever assessed for genetic studies, and 96 Caucasian patients with IgAN, were recruited for this study. Seven single nucleotide polymorphisms (SNPs) within <i>NLRP3</i> (rs4925648, rs4925659, rs10159239, rs10754558, rs4353135, rs35829419, and rs10733113) and 2 <i>CASP1</i> SNPs (rs488992 and rs501192) were genotyped using TaqMan Probes. p values &lt; 0.05 after Benjamini-Hochberg correction for an FDR of 5% were considered statistically significant. <h3>Results:</h3> No statistically significant difference was found in <i>NLRP3</i> and <i>CASP1</i> genotype and allele frequencies between patients with IgAV and patients with IgAN (Table 1). Likewise, no statistically significant differences were observed in genotype and allele frequencies in <i>NLRP3</i> and <i>CASP1</i> when comparing IgAVN patitents with IgAN patients (Table 1). Additionally, the same outcome was achieved when comparing the haplotype frequencies of IgAV and IgAVN patients to those of IgAN patients (Table 2). <h3>Conclusion:</h3> Our results suggest that neither <i>NLRP3</i> nor <i>CASP1</i> is useful for discriminating between IgAV and IgAN, nor between IgAVN and IgAN, indicating that these diseases could be similar in the inflammasome context. <h3>REFERENCES:</h3> [1] Arthritis Rheum. 2013 Jan;65(1):1-11. [2] Clin Exp Rheumatol. 2013 Jan-Feb;31(1 Suppl 75):S45-51. [3] Medicina (Kaunas). 2022 Dec 30;59(1):82. [4] Kidney Dis (Basel). 2023 Jun 24;9(6):443-458. [5] Ann Palliat Med. 2021 Jun;10(6):6687-6693. <h3>Acknowledgements:</h3> This research was funded by European Union FEDER funds and "Fondo de Investigaciones Sanitarias" from "Instituto de Salud Carlos III" (ISCIII, Health Ministry, Spain), grant number PI18/00042 and PI21/00042. JCB-L is a recipient of a PFIS programme fellowship from the ISCIII, co-funded by the European Social Fund ("Investing in your future"), grant number FI22/00020. MSM-G is supported by funds of "Fondo de Investigaciones Sanitarias" from ISCIII, grant number PI18/00042.VP-C is supported by funds of IDIVAL, grant number NVAL23/02. RL-M is a recipient of a Miguel Servet type II program fellowship from the ISCIII, co-funded by ESF ("Investing in your future"), grant number CPII21/00004. <h3>Disclosure of Interests:</h3> <b>None declared.</b>