Peter A. Nigrovic

Nov 4, 2024 | acrjournals.onlinelibrary.wiley.com | Peter A. Nigrovic

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Aug 9, 2024 | nature.com | Qiang Wang |taehyeung Kim |Marta Martínez-Bonet |Sangwan Sim |Jing Cui |Jeffrey A Sparks | +9 more

Genome-wide association studies implicate multiple loci in risk for systemic lupus erythematosus (SLE), but few contain exonic variants, rendering systematic identification of non-coding variants essential to decoding SLE genetics. We utilized SNP-seq and bioinformatic enrichment to interrogate 2180 single-nucleotide polymorphisms (SNPs) from 87 SLE risk loci for potential binding of transcription factors and related proteins from B cells. 52 SNPs that passed initial screening were tested by electrophoretic mobility shift and luciferase reporter assays. To validate the approach, we studied rs2297550 in detail, finding that the risk allele enhanced binding to the transcription factor Ikaros (encoded by IKZF1), thereby modulating expression of IKBKE. Correspondingly, primary cells from genotyped healthy donors bearing the risk allele expressed higher levels of the interferon / NF-κB regulator IKKε. Together, these findings define a set of likely functional non-coding lupus risk variants and identify a regulatory pathway involving rs2297550, Ikaros, and IKKε implicated by human genetics in risk for SLE. Here, the authors use SNP-seq to screen 87 lupus risk loci for functional non-coding variants. Validation at one locus identified a risk variant through which enhanced Ikaros binding amplifies expression of the interferon / NFκB regulator IKKε.

Apr 9, 2024 | nature.com | Peter A. Nigrovic

AbstractIn rheumatoid arthritis, juvenile idiopathic arthritis and other forms of inflammatory arthritis, the immune system targets certain joints but not others. The pattern of joints affected varies by disease and by individual, with flares most commonly involving joints that were previously inflamed. This phenomenon, termed joint-specific memory, is difficult to explain by systemic immunity alone.

Apr 4, 2024 | acrjournals.onlinelibrary.wiley.com | Daniel Solomon |Mariana J. Kaplan |Skin Diseases |Peter A. Nigrovic

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