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In this study, we investigated the humoral response against specific antigenic peptides derived from HERV-H, HERV-K, and HERV-W in the plasma of patients across different asthma phenotypes, including non-severe and severe cases, compared to healthy controls (HCs). Our results show that antibody levels against HERV-W were significantly low in the asthmatic population, showing a progressive downregulation that was more pronounced in severe cases. Conversely, a distinct and robust upregulation was uniquely observed for HERV-H in severe asthma cases, reaching a 100% positivity rate. Furthermore, HERV-K antibody levels were significantly lower in the non-severe asthmatic subtype compared to HCs. Interestingly, Spearman analysis revealed significant positive correlations among all tested HERV peptides within the Asthmatic cohort, a co-regulatory trend that became substantially reinforced within the Severe Asthma subgroup. These findings highlight a specific immune dysregulation pattern where a synchronized HERV expression tightly correlates with disease severity and phenotypical classification. The HERV epitopes identified in this exploratory study appear to be key targets of the humoral response in asthmatic patients, suggesting that circulating antibody levels against these retroviral elements could serve as potential tools for exploratory disease stratification and refractory phenotype characterization.<\/jats:p>","DOI":"10.1007\/s12026-026-09855-2","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:12:20Z","timestamp":1791443540000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Human endogenous retroviruses antibody signatures in severe asthma phenotypes"],"prefix":"10.1007","volume":"74","author":[{"given":"Milena","family":"Fais","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachele","family":"Campus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena Rita","family":"Simula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carmina","family":"Pau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Piras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Pirina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo A.","family":"Sechi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"9855_CR1","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/S0140-6736(17)33311-1","volume":"391","author":"A Papi","year":"2018","unstructured":"Papi A, Brightling C, Pedersen SE, Reddel HK. 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