{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T20:46:44Z","timestamp":1793825204485,"version":"4.6.1"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>C-reactive protein (CRP) plays a critical role in the innate immune system and serves as a biomarker for various inflammatory conditions. CRP is a dynamic protein undergoing conformational changes between pentameric (pCRP) and monomeric (mCRP) conformations. pCRP is the well-established systemic marker of inflammation, while mCRP is associated with localized tissue inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study aimed to evaluate systemic levels of pCRP, mCRP, interleukin-6 (IL-6), and interleukin-1\u03b2 (IL-1\u03b2) in patients with a variety of intraocular inflammatory conditions, including diabetic macular edema (DME) and non-infectious uveitis such as Beh\u00e7et\u2019s disease (BD), Birdshot retinochoroidopathy (BSRC), HLA-B27-associated uveitis, and undifferentiated uveitis (UU).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 77 subjects were included. mCRP levels were significantly elevated in BD, DME, and UU compared to controls (p = 0.014, p = 0.036, and p = 0.031, respectively). The mCRP\/pCRP ratio was also significantly higher in DME and UU (p = 0.035 and p = 0.011, respectively). In addition, a strong positive correlation was observed between IL-6 and IL-1\u03b2 (\u03c1 = 0.638, p &amp;lt;0.0001). No significant differences in serum levels of pCRP, IL-6, or IL-1\u03b2 were observed among the groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings suggest that mCRP, rather than pCRP, may be a more specific systemic biomarker for certain intraocular inflammatory conditions. The involvement of the CRP axis and the strong correlation between IL-6 and IL-1\u03b2 underscore the interaction of these key inflammatory mediators, providing further insight into the targeting of CRP axis for therapeutic purposes.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1601145","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T04:13:24Z","timestamp":1747023204000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["C-reactive protein conformations and their association with the IL-1\u03b2\/IL-6 pathway in ocular inflammatory conditions"],"prefix":"10.3389","volume":"16","author":[{"given":"Mercedes S.","family":"Nabaes Jodar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor","family":"Lloren\u00e7","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Figueras-Roca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maite","family":"Sainz de-la-Maza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Ad\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanca","family":"Molins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200003233421202","article-title":"C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women","volume":"342","author":"Ridker","year":"2000","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-59815-9_24","article-title":"Systemic lupus erythematosus and cytokine storm","volume":"1448","author":"Caricchio","year":"2024","journal-title":"Adv Exp Med Biol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2020.595835","article-title":"C-reactive protein and cancer-diagnostic and therapeutic insights","volume":"11","author":"Hart","year":"2020","journal-title":"Front Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"4708","DOI":"10.1038\/S41598-025-89306-4","article-title":"Severe COVID-19 disease is associated with genetic factors affecting plasma ACE2 receptor and CRP concentrations","volume":"15","author":"Vogi","year":"2025","journal-title":"Sci Rep"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R400025200","article-title":"C-reactive protein","volume":"279","author":"Black","year":"2004","journal-title":"J Biol Chem"},{"key":"B6","doi-asserted-by":"publisher","first-page":"14188","DOI":"10.1038\/ncomms14188","article-title":"Transitional changes in the CRP structure lead to the exposure of proinflammatory binding sites","volume":"8","author":"Braig","year":"2017","journal-title":"Nat Commun"},{"key":"B7","doi-asserted-by":"publisher","first-page":"22889","DOI":"10.1038\/srep22889","article-title":"Complement factor H binding of monomeric C-reactive protein downregulates proinflammatory activity and is impaired with at risk polymorphic CFH variants","volume":"6","author":"Molins","year":"2016","journal-title":"Sci Rep"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.174359","article-title":"C-reactive protein isoforms differ in their effects on thrombus growth","volume":"28","author":"Molins","year":"2008","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1161\/CIRCULATIONAHA.113.007124","article-title":"Dissociation of pentameric to monomeric C-reactive protein localizes and aggravates inflammation: In vivo proof of a powerful proinflammatory mechanism and a new anti-inflammatory strategy","volume":"130","author":"Thiele","year":"2014","journal-title":"Circulation"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01351","article-title":"Dissociation of C-reactive protein localizes and amplifies inflammation: Evidence for a direct biological role of C-reactive protein and its conformational changes","volume":"9","author":"McFadyen","year":"2018","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00057.2016","article-title":"C-reactive protein isoforms differentially affect outer blood-retinal barrier integrity and function","volume":"312","author":"Molins","year":"2017","journal-title":"Am J Physiol - 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