{"id":18293,"date":"2024-02-15T00:56:58","date_gmt":"2024-02-15T00:56:58","guid":{"rendered":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/?p=18293"},"modified":"2024-02-15T00:59:13","modified_gmt":"2024-02-15T00:59:13","slug":"discovery-mutation-severe-lopus-new-treatment","status":"publish","type":"post","link":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/discovery-mutation-severe-lopus-new-treatment\/","title":{"rendered":"How the discovery of a mutation in a young Spanish girl with severe lupus is forging the path for new treatments"},"content":{"rendered":"

How the discovery of a mutation in a young Spanish girl with severe lupus is forging the path for new treatments<\/strong><\/p>\n

A team of scientists from different parts of the world came together to investigate the cause of an unusually severe case of lupus in a seven-year-old Spanish girl. Whole genome sequencing uncovered a single genetic glitch \u2013 a point mutation in the TLR7 gene \u2013 as the putative cause of the disease. When this mutation was introduced into mice, mutant mice developed lupus-like symptoms, confirming that the point mutation they discovered was in fact causative (1). What does this mean for patients like the little Spanish girl suffering from this chronic disease? Are new targeted therapies on the horizon?<\/p>\n

Lupus <\/strong>\u2013 epidemiology, symptoms, and current treatments<\/strong><\/p>\n

Systemic lupus erythematosus (SLE), commonly referred to as lupus, is a devastating autoimmune disease affecting around 3.41 million people globally. It disproportionately affects women, with approximately 3.04 million cases compared to 0.36 million in men (2). A complex interplay between genetic factors and adaptive and innate immune system dysregulation leads to inflammation and tissue damage in lupus patients (3). Symptoms vary from person to person and can include skin rashes, notably the “butterfly rash,” as well as muscle and joint pain, anemia, fatigue, hair loss, and kidney problems (4).<\/p>\n

Due to the clinical heterogeneity of the disease, the diagnosis and treatment of lupus is often challenging. Treatment responses can be diverse and unpredictable. Thanks to earlier diagnosis and better disease management, survival has improved considerably in the last five decades (3). Current treatments include antimalarials, typically hydroxychloroquine, chronic steroids, high-dose chemotherapeutic regimens, and more recently targeted biologic therapy (3). Despite this progress, many underlying mechanisms leading to lupus remain elusive, roadblocking the development of more effective treatments and possibly a cure.<\/p>\n

\"\"<\/p>\n

Toll-like receptors (TLRs) in lupus <\/strong><\/p>\n

Toll-like receptors (TLRs) play a pivotal role in the development of lupus. TLRs, known for recognizing patterns in pathogens, are key components in both innate and adaptive immune responses. Specifically, the dysregulation of TLR7 and TLR9 signaling in B cells has been implicated in lupus’s pathogenesis (5). Genome-wide association studies have linked several TLR7 polymorphisms to lupus (6). In mice models, TLR7 overexpression causes severe lupus, whereas TLR7 deletion prevents or alleviates the disease (1,7,8).<\/p>\n

The case of a seven-year-old Spanish girl with severe lupus<\/strong><\/p>\n

In 2022, Brown and colleagues identified a gain-of-function point mutation in the TLR7 gene as the underlying cause of lupus in a seven-year-old Spanish girl with severe symptoms. Whole genome sequencing followed by bioinformatics analysis of the patient revealed a de novo, TLR7 p.Tyr264His (Y264H) missense variant. Figure 1A-B shows the TLR7 variants in the patient’s family identified by Sanger sequencing using the Big Dye Terminator Cycle sequencing kit v3.1 on the 3730 DNA Analyze system (1).<\/p>\n

To determine whether the identified genetic variant \u2013 TLR7Y264H<\/sup> \u2013 causes lupus, the investigators the mutation in mice through CRISPR\u2013Cas9 editing. The mutant mice developed autoimmune symptoms and end organ damage. This was the first instance where a TLR7 genetic variations were identified as the cause of lupus in humans (1).<\/p>\n

\"\"<\/p>\n

Figure 1: TLR7 variants in the family of a Spanish child diagnosed with severe lupus at the age of seven (A) identified by Sanger sequencing using the Big Dye Terminator Cycle sequencing kit v3.1 (Applied Biosystems) on the 3730 DNA Analyze (Applied Biosystems) system (B). Sanger sequencing workflow (C). <\/strong><\/p>\n

From discovery to clinic \u2013 TLR inhibition as an emerging treatment modality<\/strong><\/p>\n

In 2023, Hawtin et al. published preclinical characterization of MHV370, an orally-administered TLR7\/8 antagonist, for lupus therapy. They showed that in human and mouse cells, MHV370 inhibits TLR7\/8-dependent production of cytokines, in particular interferon-\u03b1, a known contributor to autoimmune diseases (9).<\/p>\n

For example, the team showed that MHV370 suppresses chronic TLR7-dependent immune activation in in vivo mouse models (9). Transcriptomic profiling via amplicon sequencing (Ion AmpliSeq Transcriptome Mouse Gene Expression Kit, Thermo Fisher Scientific) using blood obtained from three groups of mice [(1) na\u00efve, (2) 14 days R848-treated (TLR7 agonist), (3) 14 days R848-treated + MHV370 from day seven onwards] showed MHV370 suppression of chronic TLR7-dependent immune activation in mice.\u00a0 In the R848-only group, several inflammatory pathways were shown to be activated. In the group treated with R848 and MHV370 from day seven onwards, the activated inflammatory pathways were downregulated, demonstrating that MHV370 can normalize pro-inflammatory parameters in a state of chronic TLR7 activation (see data here: \u00a0https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10213863\/figure\/fig3\/<\/a>)<\/p>\n

The team further showed that MHV370 prevented and halted the development of the disease in a mouse model of lupus. The results from this preclinical study establish TLR7\/8 inhibition as a promising treatment modality for lupus (9). A phase 2 study is underway evaluating MHV370’s safety, tolerability, and efficacy in two other autoimmune diseases (10).<\/p>\n

To learn more about how Applied Biosystems solutions are enabling translational research into rare and inherited diseases, visit thermofisher.com\/abraredisease<\/a>.<\/p>\n

References:<\/p>\n

    \n
  1. Brown GJ, Ca\u00f1ete PF, Wang H, Medhavy A, Bones J, Roco JA, He Y, Qin Y, Cappello J, Ellyard JI, Bassett K, Shen Q, Burgio G, Zhang Y, Turnbull C, Meng X, Wu P, Cho E, Miosge LA, Andrews TD, Field MA, Tvorogov D, Lopez AF, Babon JJ, L\u00f3pez CA, G\u00f3nzalez-Murillo \u00c1, Garulo DC, Pascual V, Levy T, Mallack EJ, Calame DG, Lotze T, Lupski JR, Ding H, Ullah TR, Walters GD, Koina ME, Cook MC, Shen N, de Lucas Collantes C, Corry B, Gantier MP, Athanasopoulos V, Vinuesa CG. TLR7 gain-of-function genetic variation causes human lupus. Nature. 2022 May;605(7909):349-356. doi: 10.1038\/s41586-022-04642-z. Epub 2022 Apr 27. PMID: 35477763; PMCID: PMC9095492.<\/li>\n
  2. Tian J, Zhang D, Yao X, Huang Y, Lu Q. Global epidemiology of systemic lupus erythematosus: a comprehensive systematic analysis and modelling study. Ann Rheum Dis. 2023 Mar;82(3):351-356. doi: 10.1136\/ard-2022-223035. Epub 2022 Oct 14. PMID: 36241363; PMCID: PMC9933169.<\/li>\n
  3. Lazar S, Kahlenberg JM. Systemic Lupus Erythematosus: New Diagnostic and Therapeutic Approaches. Annu Rev Med. 2023 Jan 27;74:339-352. doi: 10.1146\/annurev-med-043021-032611. Epub 2022 Jul 8. PMID: 35804480.<\/li>\n
  4. Lupus symptoms: https:\/\/www.cdc.gov\/lupus\/basics\/symptoms.htm<\/a><\/li>\n
  5. Wen L, Zhang B, Wu X, Liu R, Fan H, Han L, Zhang Z, Ma X, Chu CQ, Shi X. Toll-like receptors 7 and 9 regulate the proliferation and differentiation of B cells in systemic lupus erythematosus. Front Immunol. 2023 Feb 15;14:1093208. doi: 10.3389\/fimmu.2023.1093208. PMID: 36875095; PMCID: PMC9975558.<\/li>\n
  6. Celhar T, Fairhurst AM. Toll-like receptors in systemic lupus erythematosus: potential for personalized treatment. Front Pharmacol. 2014 Dec 8;5:265. doi: 10.3389\/fphar.2014.00265. PMID: 25538618; PMCID: PMC4258990.<\/li>\n
  7. Pisitkun P, Deane JA, Difilippantonio MJ, Tarasenko T, Satterthwaite AB, Bolland S. Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication. Science. 2006 Jun 16;312(5780):1669-72. doi: 10.1126\/science.1124978. Epub 2006 May 18. PMID: 16709748.<\/li>\n
  8. Berland R, Fernandez L, Kari E, Han JH, Lomakin I, Akira S, Wortis HH, Kearney JF, Ucci AA, Imanishi-Kari T. Toll-like receptor 7-dependent loss of B cell tolerance in pathogenic autoantibody knockin mice. Immunity. 2006 Sep;25(3):429-40. doi: 10.1016\/j.immuni.2006.07.014. PMID: 16973388.<\/li>\n
  9. Hawtin S, Andr\u00e9 C, Collignon-Zipfel G, Appenzeller S, Bannert B, Baumgartner L, Beck D, Betschart C, Boulay T, Brunner HI, Ceci M, Deane J, Feifel R, Ferrero E, Kyburz D, Lafossas F, Loetscher P, Merz-Stoeckle C, Michellys P, Nuesslein-Hildesheim B, Raulf F, Rush JS, Ruzzante G, Stein T, Zaharevitz S, Wieczorek G, Siegel R, Gergely P, Shisha T, Junt T. Preclinical characterization of the Toll-like receptor 7\/8 antagonist MHV370 for lupus therapy. Cell Rep Med. 2023 May 16;4(5):101036. doi: 10.1016\/j.xcrm.2023.101036. PMID: 37196635; PMCID: PMC10213863.<\/li>\n
  10. A study to evaluate the safety, tolerability and efficacy of MHV370 in participants with Sjogren’s Syndrome (SjS) or Mixed Connective Tissue Disease (MCTD): https:\/\/classic.clinicaltrials.gov\/ct2\/show\/NCT04988087<\/a><\/li>\n<\/ol>\n

     <\/p>\n","protected":false},"excerpt":{"rendered":"

    How the discovery of a mutation in a young Spanish girl with severe lupus is forging the path for new treatments A team of scientists from different parts of the world came together to investigate the cause of an unusually severe case of lupus in a seven-year-old Spanish girl. Whole genome sequencing uncovered a single<\/p>\n","protected":false},"author":120,"featured_media":18296,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_kad_blocks_custom_css":"","_kad_blocks_head_custom_js":"","_kad_blocks_body_custom_js":"","_kad_blocks_footer_custom_js":"","_monsterinsights_skip_tracking":false,"_genesis_hide_title":false,"_genesis_hide_breadcrumbs":false,"_genesis_hide_singular_image":false,"_genesis_hide_footer_widgets":false,"_genesis_custom_body_class":"","_genesis_custom_post_class":"","_genesis_layout":"","_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[181],"tags":[2380,17,2379],"division":[],"class_list":{"0":"post-18293","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-inherited-diseases","8":"tag-applied","9":"tag-applied-biosystems","10":"tag-autoimmune","11":"entry"},"_selected_authors":"","_selected_reviewers":"","acf":[],"yoast_head":"\nHow the discovery of a mutation in a young Spanish girl with severe lupus is forging the path for new treatments - Behind the Bench<\/title>\n<meta name=\"description\" content=\"A team of scientists from different parts of the world came together to investigate the cause of an unusually severe case of lupus in a seven-year-old Spanish girl.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.thermofisher.com\/blog\/behindthebench\/discovery-mutation-severe-lopus-new-treatment\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"How the discovery of a mutation in a young Spanish girl with severe lupus is forging the path for new treatments\" \/>\n<meta property=\"og:description\" content=\"A team of scientists from different parts of the world came together to investigate the cause of an unusually severe case of lupus in a seven-year-old Spanish girl.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.thermofisher.com\/blog\/behindthebench\/discovery-mutation-severe-lopus-new-treatment\/\" \/>\n<meta property=\"og:site_name\" content=\"Behind the Bench\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/thermofisher\" \/>\n<meta property=\"article:published_time\" content=\"2024-02-15T00:56:58+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-02-15T00:59:13+00:00\" \/>\n<meta property=\"og:image\" content=\"http:\/\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2024\/02\/lupus_shutterstock_19139989601200x675.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"1200\" \/>\n\t<meta property=\"og:image:height\" content=\"675\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Behind The Bench Staff\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@thermofisher\" \/>\n<meta name=\"twitter:site\" content=\"@thermofisher\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Behind The Bench Staff\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"6 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/www.thermofisher.com\\\/blog\\\/behindthebench\\\/discovery-mutation-severe-lopus-new-treatment\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.thermofisher.com\\\/blog\\\/behindthebench\\\/discovery-mutation-severe-lopus-new-treatment\\\/\"},\"author\":{\"name\":\"Behind The Bench Staff\",\"@id\":\"https:\\\/\\\/admin.acceleratingscience.com\\\/behindthebench\\\/#\\\/schema\\\/person\\\/9bbb2d67616274d3d4a21a584f7f4a0c\"},\"headline\":\"How the discovery of a mutation in a young Spanish girl with severe lupus is forging the path for new treatments\",\"datePublished\":\"2024-02-15T00:56:58+00:00\",\"dateModified\":\"2024-02-15T00:59:13+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/www.thermofisher.com\\\/blog\\\/behindthebench\\\/discovery-mutation-severe-lopus-new-treatment\\\/\"},\"wordCount\":1254,\"commentCount\":0,\"image\":{\"@id\":\"https:\\\/\\\/www.thermofisher.com\\\/blog\\\/behindthebench\\\/discovery-mutation-severe-lopus-new-treatment\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/admin.acceleratingscience.com\\\/behindthebench\\\/wp-content\\\/uploads\\\/sites\\\/9\\\/2024\\\/02\\\/lupus_shutterstock_19139989601200x675.jpg\",\"keywords\":[\"applied\",\"Applied Biosystems\",\"autoimmune\"],\"articleSection\":[\"Inherited Diseases\"],\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"CommentAction\",\"name\":\"Comment\",\"target\":[\"https:\\\/\\\/www.thermofisher.com\\\/blog\\\/behindthebench\\\/discovery-mutation-severe-lopus-new-treatment\\\/#respond\"]}]},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.thermofisher.com\\\/blog\\\/behindthebench\\\/discovery-mutation-severe-lopus-new-treatment\\\/\",\"url\":\"https:\\\/\\\/www.thermofisher.com\\\/blog\\\/behindthebench\\\/discovery-mutation-severe-lopus-new-treatment\\\/\",\"name\":\"How the discovery of a mutation in a young Spanish girl with severe lupus is forging the path for new treatments - Behind the Bench\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/admin.acceleratingscience.com\\\/behindthebench\\\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\\\/\\\/www.thermofisher.com\\\/blog\\\/behindthebench\\\/discovery-mutation-severe-lopus-new-treatment\\\/#primaryimage\"},\"image\":{\"@id\":\"https:\\\/\\\/www.thermofisher.com\\\/blog\\\/behindthebench\\\/discovery-mutation-severe-lopus-new-treatment\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/admin.acceleratingscience.com\\\/behindthebench\\\/wp-content\\\/uploads\\\/sites\\\/9\\\/2024\\\/02\\\/lupus_shutterstock_19139989601200x675.jpg\",\"datePublished\":\"2024-02-15T00:56:58+00:00\",\"dateModified\":\"2024-02-15T00:59:13+00:00\",\"author\":{\"@id\":\"https:\\\/\\\/admin.acceleratingscience.com\\\/behindthebench\\\/#\\\/schema\\\/person\\\/9bbb2d67616274d3d4a21a584f7f4a0c\"},\"description\":\"A team of scientists from different parts of the world came together to investigate the cause of an unusually severe case of lupus in a seven-year-old Spanish girl.\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/www.thermofisher.com\\\/blog\\\/behindthebench\\\/discovery-mutation-severe-lopus-new-treatment\\\/#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/www.thermofisher.com\\\/blog\\\/behindthebench\\\/discovery-mutation-severe-lopus-new-treatment\\\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\\\/\\\/www.thermofisher.com\\\/blog\\\/behindthebench\\\/discovery-mutation-severe-lopus-new-treatment\\\/#primaryimage\",\"url\":\"https:\\\/\\\/admin.acceleratingscience.com\\\/behindthebench\\\/wp-content\\\/uploads\\\/sites\\\/9\\\/2024\\\/02\\\/lupus_shutterstock_19139989601200x675.jpg\",\"contentUrl\":\"https:\\\/\\\/admin.acceleratingscience.com\\\/behindthebench\\\/wp-content\\\/uploads\\\/sites\\\/9\\\/2024\\\/02\\\/lupus_shutterstock_19139989601200x675.jpg\",\"width\":1200,\"height\":675},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/www.thermofisher.com\\\/blog\\\/behindthebench\\\/discovery-mutation-severe-lopus-new-treatment\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/admin.acceleratingscience.com\\\/behindthebench\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"How the discovery of a mutation in a young Spanish girl with severe lupus is forging the path for new treatments\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/admin.acceleratingscience.com\\\/behindthebench\\\/#website\",\"url\":\"https:\\\/\\\/admin.acceleratingscience.com\\\/behindthebench\\\/\",\"name\":\"Behind the Bench\",\"description\":\"\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/admin.acceleratingscience.com\\\/behindthebench\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"en-US\"},{\"@type\":\"Person\",\"@id\":\"https:\\\/\\\/admin.acceleratingscience.com\\\/behindthebench\\\/#\\\/schema\\\/person\\\/9bbb2d67616274d3d4a21a584f7f4a0c\",\"name\":\"Behind The Bench Staff\",\"image\":{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\\\/\\\/secure.gravatar.com\\\/avatar\\\/52d5c16ece4bd1c0a49a63521c2b6a25c54a3f0c33f7afed215ba7e0cdff69e3?s=96&d=mm&r=g\",\"url\":\"https:\\\/\\\/secure.gravatar.com\\\/avatar\\\/52d5c16ece4bd1c0a49a63521c2b6a25c54a3f0c33f7afed215ba7e0cdff69e3?s=96&d=mm&r=g\",\"contentUrl\":\"https:\\\/\\\/secure.gravatar.com\\\/avatar\\\/52d5c16ece4bd1c0a49a63521c2b6a25c54a3f0c33f7afed215ba7e0cdff69e3?s=96&d=mm&r=g\",\"caption\":\"Behind The Bench Staff\"},\"url\":\"https:\\\/\\\/admin.acceleratingscience.com\\\/author\\\/behind-the-bench-staff\\\/\"}]}<\/script>\n<!-- \/ Yoast SEO Premium plugin. -->","yoast_head_json":{"title":"How the discovery of a mutation in a young Spanish girl with severe lupus is forging the path for new treatments - Behind the Bench","description":"A team of scientists from different parts of the world came together to investigate the cause of an unusually severe case of lupus in a seven-year-old Spanish girl.","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/discovery-mutation-severe-lopus-new-treatment\/","og_locale":"en_US","og_type":"article","og_title":"How the discovery of a mutation in a young Spanish girl with severe lupus is forging the path for new treatments","og_description":"A team of scientists from different parts of the world came together to investigate the cause of an unusually severe case of lupus in a seven-year-old Spanish girl.","og_url":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/discovery-mutation-severe-lopus-new-treatment\/","og_site_name":"Behind the Bench","article_publisher":"https:\/\/www.facebook.com\/thermofisher","article_published_time":"2024-02-15T00:56:58+00:00","article_modified_time":"2024-02-15T00:59:13+00:00","og_image":[{"width":1200,"height":675,"url":"http:\/\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2024\/02\/lupus_shutterstock_19139989601200x675.jpg","type":"image\/jpeg"}],"author":"Behind The Bench Staff","twitter_card":"summary_large_image","twitter_creator":"@thermofisher","twitter_site":"@thermofisher","twitter_misc":{"Written by":"Behind The Bench Staff","Est. reading time":"6 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/discovery-mutation-severe-lopus-new-treatment\/#article","isPartOf":{"@id":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/discovery-mutation-severe-lopus-new-treatment\/"},"author":{"name":"Behind The Bench Staff","@id":"https:\/\/admin.acceleratingscience.com\/behindthebench\/#\/schema\/person\/9bbb2d67616274d3d4a21a584f7f4a0c"},"headline":"How the discovery of a mutation in a young Spanish girl with severe lupus is forging the path for new treatments","datePublished":"2024-02-15T00:56:58+00:00","dateModified":"2024-02-15T00:59:13+00:00","mainEntityOfPage":{"@id":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/discovery-mutation-severe-lopus-new-treatment\/"},"wordCount":1254,"commentCount":0,"image":{"@id":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/discovery-mutation-severe-lopus-new-treatment\/#primaryimage"},"thumbnailUrl":"https:\/\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2024\/02\/lupus_shutterstock_19139989601200x675.jpg","keywords":["applied","Applied Biosystems","autoimmune"],"articleSection":["Inherited Diseases"],"inLanguage":"en-US","potentialAction":[{"@type":"CommentAction","name":"Comment","target":["https:\/\/www.thermofisher.com\/blog\/behindthebench\/discovery-mutation-severe-lopus-new-treatment\/#respond"]}]},{"@type":"WebPage","@id":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/discovery-mutation-severe-lopus-new-treatment\/","url":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/discovery-mutation-severe-lopus-new-treatment\/","name":"How the discovery of a mutation in a young Spanish girl with severe lupus is forging the path for new treatments - Behind the Bench","isPartOf":{"@id":"https:\/\/admin.acceleratingscience.com\/behindthebench\/#website"},"primaryImageOfPage":{"@id":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/discovery-mutation-severe-lopus-new-treatment\/#primaryimage"},"image":{"@id":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/discovery-mutation-severe-lopus-new-treatment\/#primaryimage"},"thumbnailUrl":"https:\/\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2024\/02\/lupus_shutterstock_19139989601200x675.jpg","datePublished":"2024-02-15T00:56:58+00:00","dateModified":"2024-02-15T00:59:13+00:00","author":{"@id":"https:\/\/admin.acceleratingscience.com\/behindthebench\/#\/schema\/person\/9bbb2d67616274d3d4a21a584f7f4a0c"},"description":"A team of scientists from different parts of the world came together to investigate the cause of an unusually severe case of lupus in a seven-year-old Spanish girl.","breadcrumb":{"@id":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/discovery-mutation-severe-lopus-new-treatment\/#breadcrumb"},"inLanguage":"en-US","potentialAction":[{"@type":"ReadAction","target":["https:\/\/www.thermofisher.com\/blog\/behindthebench\/discovery-mutation-severe-lopus-new-treatment\/"]}]},{"@type":"ImageObject","inLanguage":"en-US","@id":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/discovery-mutation-severe-lopus-new-treatment\/#primaryimage","url":"https:\/\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2024\/02\/lupus_shutterstock_19139989601200x675.jpg","contentUrl":"https:\/\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2024\/02\/lupus_shutterstock_19139989601200x675.jpg","width":1200,"height":675},{"@type":"BreadcrumbList","@id":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/discovery-mutation-severe-lopus-new-treatment\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/admin.acceleratingscience.com\/behindthebench\/"},{"@type":"ListItem","position":2,"name":"How the discovery of a mutation in a young Spanish girl with severe lupus is forging the path for new treatments"}]},{"@type":"WebSite","@id":"https:\/\/admin.acceleratingscience.com\/behindthebench\/#website","url":"https:\/\/admin.acceleratingscience.com\/behindthebench\/","name":"Behind the Bench","description":"","potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/admin.acceleratingscience.com\/behindthebench\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"en-US"},{"@type":"Person","@id":"https:\/\/admin.acceleratingscience.com\/behindthebench\/#\/schema\/person\/9bbb2d67616274d3d4a21a584f7f4a0c","name":"Behind The Bench Staff","image":{"@type":"ImageObject","inLanguage":"en-US","@id":"https:\/\/secure.gravatar.com\/avatar\/52d5c16ece4bd1c0a49a63521c2b6a25c54a3f0c33f7afed215ba7e0cdff69e3?s=96&d=mm&r=g","url":"https:\/\/secure.gravatar.com\/avatar\/52d5c16ece4bd1c0a49a63521c2b6a25c54a3f0c33f7afed215ba7e0cdff69e3?s=96&d=mm&r=g","contentUrl":"https:\/\/secure.gravatar.com\/avatar\/52d5c16ece4bd1c0a49a63521c2b6a25c54a3f0c33f7afed215ba7e0cdff69e3?s=96&d=mm&r=g","caption":"Behind The Bench Staff"},"url":"https:\/\/admin.acceleratingscience.com\/author\/behind-the-bench-staff\/"}]}},"taxonomy_info":{"category":[{"value":181,"label":"Inherited Diseases"}],"post_tag":[{"value":2380,"label":"applied"},{"value":17,"label":"Applied Biosystems"},{"value":2379,"label":"autoimmune"}]},"featured_image_src_large":["https:\/\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2024\/02\/lupus_shutterstock_19139989601200x675-1024x576.jpg",760,428,true],"author_info":{"display_name":"Behind The Bench Staff","author_link":"https:\/\/admin.acceleratingscience.com\/author\/behind-the-bench-staff\/"},"comment_info":42,"category_info":[{"term_id":181,"name":"Inherited Diseases","slug":"inherited-diseases","term_group":0,"term_taxonomy_id":181,"taxonomy":"category","description":"","parent":0,"count":26,"filter":"raw","meta":[],"cat_ID":181,"category_count":26,"category_description":"","cat_name":"Inherited Diseases","category_nicename":"inherited-diseases","category_parent":0}],"tag_info":[{"term_id":2380,"name":"applied","slug":"applied","term_group":0,"term_taxonomy_id":2380,"taxonomy":"post_tag","description":"","parent":0,"count":1,"filter":"raw","meta":[]},{"term_id":17,"name":"Applied Biosystems","slug":"applied-biosystems","term_group":0,"term_taxonomy_id":17,"taxonomy":"post_tag","description":"","parent":0,"count":193,"filter":"raw","meta":[]},{"term_id":2379,"name":"autoimmune","slug":"autoimmune","term_group":0,"term_taxonomy_id":2379,"taxonomy":"post_tag","description":"","parent":0,"count":1,"filter":"raw","meta":[]}],"jetpack-related-posts":[{"id":19168,"url":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/understanding-dna-melting-analysis-using-uv-visible-spectroscopy\/","url_meta":{"origin":18293,"position":0},"title":"Understanding DNA Melting Analysis Using UV-Visible Spectroscopy","author":"Marlene Gasdia-Cochrane","date":"October 14, 2025","format":false,"excerpt":"DNA melting analysis is a vital molecular biology technique used to study the stability and properties of DNA by monitoring its transition from double-stranded to single-stranded form with increasing temperature. UV-visible spectroscopy measures changes in DNA absorbance during this process, providing insights into DNA stability, sequence composition, and molecular interactions.\u2026","rel":"","context":"In "Pharma & Biotech Manufacturing"","block_context":{"text":"Pharma & Biotech Manufacturing","link":"https:\/\/admin.acceleratingscience.com\/behindthebench\/pharmamfg\/"},"img":{"alt_text":"Close-up Of Dna Molecule On Blue Background","src":"https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2025\/10\/iStock-2200215349.jpg?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2025\/10\/iStock-2200215349.jpg?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2025\/10\/iStock-2200215349.jpg?resize=525%2C300&ssl=1 1.5x, https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2025\/10\/iStock-2200215349.jpg?resize=700%2C400&ssl=1 2x, https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2025\/10\/iStock-2200215349.jpg?resize=1050%2C600&ssl=1 3x, https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2025\/10\/iStock-2200215349.jpg?resize=1400%2C800&ssl=1 4x"},"classes":[]},{"id":19579,"url":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/liquid-biopsy-cancer-research-ngs-pcr\/","url_meta":{"origin":18293,"position":1},"title":"From Discovery to Monitoring: How Sequencing and PCR Work Together in Oncology Research","author":"Behind The Bench Staff","date":"March 24, 2026","format":false,"excerpt":"Scientific, joins the Absolute Gene-ius podcast to discuss how molecular technologies are advancing precision oncology research. With experience spanning clinical laboratory research, digital PCR research applications, and next-generation sequencing (NGS), Dr. Sollweck shares how scientists are addressing critical unmet needs in cancer research. From liquid biopsy research strategies to minimal\u2026","rel":"","context":"In "Cancer Research"","block_context":{"text":"Cancer Research","link":"https:\/\/admin.acceleratingscience.com\/behindthebench\/cancer-research\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2026\/03\/Sollweck-headshot-200x250_Jordan-Ruggieri.jpeg?resize=350%2C200&ssl=1","width":350,"height":200},"classes":[]},{"id":19345,"url":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/precision-oncology-diagnostics\/","url_meta":{"origin":18293,"position":2},"title":"The Expanding Role of Molecular Diagnostics in Precision Oncology","author":"Behind The Bench Staff","date":"January 13, 2026","format":false,"excerpt":"https:\/\/www.youtube.com\/watch?v=F6FfHIizJBY For Dr. Harald Bartsch, a clinical pathologist in southern Bavaria, molecular diagnostic tools have become an indispensable part of his arsenal. \u201cI believe molecular diagnostics play a crucial role in modern oncology, and I see this as the direction everything is headed,\u201d says Dr. Bartsch. While immunohistochemistry remains central\u2026","rel":"","context":"In "Cancer Research"","block_context":{"text":"Cancer Research","link":"https:\/\/admin.acceleratingscience.com\/behindthebench\/cancer-research\/"},"img":{"alt_text":"Clinical Pathologist in a Molecular Diagnostics Laboratory","src":"https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2026\/01\/Bartsch-1.jpg?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2026\/01\/Bartsch-1.jpg?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2026\/01\/Bartsch-1.jpg?resize=525%2C300&ssl=1 1.5x, https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2026\/01\/Bartsch-1.jpg?resize=700%2C400&ssl=1 2x"},"classes":[]},{"id":19447,"url":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/philadelphia-chromosome-like-all-digital-pcr\/","url_meta":{"origin":18293,"position":3},"title":"Unlocking Cancer\u2019s Genetic Secrets with Digital PCR","author":"Behind The Bench Staff","date":"February 27, 2026","format":false,"excerpt":"In this episode of Absolute Gene-ius, we explore how digital PCR (dPCR) is transforming leukemia research with Valeria Rangel, a PhD candidate at the University of California, Irvine. Her work focuses on Philadelphia chromosome-like (Ph-like) B-cell acute lymphoblastic leukemia (ALL), a rare, aggressive subtype that disproportionately affects Hispanic populations. By\u2026","rel":"","context":"In "Cancer Research"","block_context":{"text":"Cancer Research","link":"https:\/\/admin.acceleratingscience.com\/behindthebench\/cancer-research\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2025\/11\/RANGEL-headshot-1.jpg?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2025\/11\/RANGEL-headshot-1.jpg?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2025\/11\/RANGEL-headshot-1.jpg?resize=525%2C300&ssl=1 1.5x, https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2025\/11\/RANGEL-headshot-1.jpg?resize=700%2C400&ssl=1 2x"},"classes":[]},{"id":19232,"url":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/early-molecular-relapse-detection-dpcr\/","url_meta":{"origin":18293,"position":4},"title":"Following the Molecular Fingerprints of Cancer with Digital PCR","author":"Behind The Bench Staff","date":"November 11, 2025","format":false,"excerpt":"https:\/\/www.youtube.com\/watch?v=vbta1TG617s For clinical researchers and scientists, the value of a biomarker depends on its accurate measurement and trackability over time. Digital PCR (dPCR) delivers both. At Tata Medical Center, Dr. Mayur Parihar, Senior Consultant in Hematology and Cytogenetics and Clinical Research Scientist at the Tata Translational Cancer Research Center, recognizes\u2026","rel":"","context":"In "Cancer Research"","block_context":{"text":"Cancer Research","link":"https:\/\/admin.acceleratingscience.com\/behindthebench\/cancer-research\/"},"img":{"alt_text":"Pathologist preparing a molecular diagnostic sample in a clinical laboratory to support precision oncology decision-making.","src":"https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2026\/01\/LC-Blog_Preferred-1.jpg?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2026\/01\/LC-Blog_Preferred-1.jpg?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2026\/01\/LC-Blog_Preferred-1.jpg?resize=525%2C300&ssl=1 1.5x, https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2026\/01\/LC-Blog_Preferred-1.jpg?resize=700%2C400&ssl=1 2x"},"classes":[]},{"id":19676,"url":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/avian-influenza-qpcr-assay-failure\/","url_meta":{"origin":18293,"position":5},"title":"Avian Influenza qPCR Testing: How Viral Evolution Contributes to Assay Failure\u2014and How Labs Can Stay Ahead","author":"Behind The Bench Staff","date":"May 1, 2026","format":false,"excerpt":"Molecular veterinary diagnostic laboratories rely on reverse transcriptase real-time PCR (RT qPCR) assays to detect avian influenza virus (AIV) quickly and accurately. These assays are central to surveillance programs, outbreak response, and disease control\u2014particularly for highly pathogenic avian influenza (HPAI) strains such as H5Nx. As Influenza A viruses continue to\u2026","rel":"","context":"In "Animal Health and AgriGenomics"","block_context":{"text":"Animal Health and AgriGenomics","link":"https:\/\/admin.acceleratingscience.com\/behindthebench\/animal-health-and-agrigenomics\/"},"img":{"alt_text":"Chickens in a flock on a farm representing poultry populations monitored for avian influenza surveillance.","src":"https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2026\/05\/Untitled-3.png?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2026\/05\/Untitled-3.png?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2026\/05\/Untitled-3.png?resize=525%2C300&ssl=1 1.5x, https:\/\/i0.wp.com\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2026\/05\/Untitled-3.png?resize=700%2C400&ssl=1 2x"},"classes":[]}],"jetpack_sharing_enabled":true,"jetpack_featured_media_url":"https:\/\/admin.acceleratingscience.com\/behindthebench\/wp-content\/uploads\/sites\/9\/2024\/02\/lupus_shutterstock_19139989601200x675.jpg","_links":{"self":[{"href":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/wp-json\/wp\/v2\/posts\/18293","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/wp-json\/wp\/v2\/users\/120"}],"replies":[{"embeddable":true,"href":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/wp-json\/wp\/v2\/comments?post=18293"}],"version-history":[{"count":0,"href":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/wp-json\/wp\/v2\/posts\/18293\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/wp-json\/wp\/v2\/media\/18296"}],"wp:attachment":[{"href":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/wp-json\/wp\/v2\/media?parent=18293"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/wp-json\/wp\/v2\/categories?post=18293"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/wp-json\/wp\/v2\/tags?post=18293"},{"taxonomy":"division","embeddable":true,"href":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/wp-json\/wp\/v2\/division?post=18293"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}