{"id":218553,"date":"2025-09-11T16:05:11","date_gmt":"2025-09-11T16:05:11","guid":{"rendered":"https:\/\/www.europesays.com\/us\/218553\/"},"modified":"2025-09-11T16:05:11","modified_gmt":"2025-09-11T16:05:11","slug":"clues-for-inborn-errors-of-immunity","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/us\/218553\/","title":{"rendered":"Clues for Inborn Errors of Immunity"},"content":{"rendered":"

Behind every unexplained medical condition is a patient hoping for clarity and understanding. For people with suspected inborn errors of immunity (IEIs), genetic testing can facilitate individually tailored and effective diagnostics and treatments. However, it can also add a layer of complexity. Instead of simple answers, patients may be informed of gene variants of uncertain significance (VUS) \u2013 DNA changes that scientists can detect but, at this time, lack enough evidence to classify as harmful or harmless. A new paper from Yale School of Medicine (YSM) researchers, published in Clinical Immunology<\/a>, reframes these findings, suggesting that VUS may offer important clinical insights that deserve closer attention.<\/p>\n

According to the study\u2019s senior author, Junghee Jenny Shin, MD, PhD<\/a>, assistant professor of medicine (rheumatology, allergy and immunology) at YSM and director of Yale Medicine\u2019s Primary Immunodeficiency Program, about 80% of patients undergoing genetic testing for IEIs obtain a VUS, a result that can be frustrating for patients. Individuals with IEIs are born with impaired or dysregulated immune systems, often suffering from recurrent or severe infections, autoimmune disease, autoinflammatory conditions, certain cancers, and other complications. <\/p>\n

<\/p>\n

\u201cTraditional guidelines say you should not treat patients based on a VUS, so most of the time we set these findings aside,\u201d says Shin. \u201cYet we often notice that these variants seem to align with patients\u2019 clinical pictures. We began to wonder if there was a better way to classify them that could be more useful for clinicians and patients.\u201d <\/p>\n

In the study, the researchers identified more than 200 VUS in patients with suspected IEIs and organized them into clusters based on gene function. They found that these clusters correlated with specific clinical features in the patients, supporting the idea that VUS may have meaningful patterns rather than being incidental findings. <\/p>\n

The strongest associations emerged in the VUS clusters linked to the adaptive immune system \u2014 those involving B cells, which help make antibodies, and T cells, which help regulate and direct immune responses. \u201cVUS in the B-cell group appeared more often in patients with recurrent respiratory infections and those who needed treatments like antibody (Immunoglobulin G) replacement therapy,\u201d says Shin. \u201cIn the T-cell group, we saw more evidence of overactive immune responses and autoimmune problems, which fits with what we know about T-cell biology.\u201d <\/p>\n

According to Shin, this is the first study to cluster VUS within IEI patients and look for their associations with clinical features. In contrast, most prior studies in this field have focused on functional experiments, in which a candidate gene is directly edited in the laboratory to understand the effect of a specific variant.<\/p>\n

\u201cFunctional studies are still the gold standard, but they\u2019re difficult to carry out in everyday clinical practice,\u201d says Shin. \u201cOur study doesn\u2019t replace them or define the significance of individual variants, but it shows that by looking at VUS together, we may start to uncover patterns that are worth further investigation. and bring us closer to better treatments for our patients.\u201d <\/p>\n

Notably, this study brought together a broad team across YSM, reflecting a shared effort to provide answers for patients with IEIs. \u201cThis was truly a group effort, with trainees and faculty from across the department working together,\u201d says Shin. \u201cBy collaborating across disciplines, especially among the members of the clinical allergy and immunology team, we were able to turn questions from the clinic into insights that bring us closer to understanding our patients.\u201d <\/p>\n

Other Yale authors of the study include Samantha Novotny<\/a>, Noelle Yoo, Jiaye Chen, Michael Granoth, Anita Kohli-Pamnani<\/a>, Florence Ida Hsu<\/a>, Mario Rodenas<\/a>, Ryan Steele<\/a>, Kelsey Kaman<\/a>, Gary Soffer<\/a>, Christina Price<\/a>, John Kuster<\/a>, Insoo Kang<\/a>, and Lais Osmani<\/a>. <\/p>\n

Rheumatology, Allergy and Immunology, one of 10 sections in the Yale Department of Internal Medicine, is dedicated to providing care for patients with rheumatic, allergic and immunologic disorders; educating future generations of thought leaders in the field; and researching fundamental questions of autoimmunity and immunology. To learn more, visit Rheumatology, Allergy and Immunology.<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"Behind every unexplained medical condition is a patient hoping for clarity and understanding. For people with suspected inborn…\n","protected":false},"author":3,"featured_media":218554,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[26],"tags":[815,159,67,132,68],"class_list":{"0":"post-218553","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-genetics","8":"tag-genetics","9":"tag-science","10":"tag-united-states","11":"tag-unitedstates","12":"tag-us"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@us\/115186520864643325","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts\/218553","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/comments?post=218553"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts\/218553\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/media\/218554"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/media?parent=218553"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/categories?post=218553"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/tags?post=218553"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}