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Such disease\u2010associated PTMs are formed under conditions of metabolic stress, renal failure, smoking, or pollutants. Importantly, several of these PTMs have recently been shown to have the capacity to activate the complement system directly. These PTMs recruit C1q or Ficolin\u20103, thereby initiating complement activation. This induces on the one hand opsonins for clearance of (cellular) debris and on the other hand the production of inflammatory mediators. In many autoimmune diseases, patients develop a variety of autoantibodies against PTMs, further amplifying complement activation on PTM\u2010proteins. Notably, anti\u2010PTM antibodies are also present, albeit in lower concentrations, in diseases that are not characterized as typical autoimmune diseases. We therefore hypothesize that PTM\u2010driven complement activation is an underlying factor for chronic low\u2010level inflammation, thereby predisposing individuals to cardiovascular and metabolic diseases. In addition, the presence of complement activation fragments on PTM\u2010proteins may facilitate the breakdown of immune tolerance towards PTM\u2010proteins, further facilitating the production of anti\u2010PTM autoantibodies. Finally, several interventions are discussed that either decrease the PTM\u2010proteins or provide targeted complement inhibition specifically on PTM\u2010proteins. Altogether, complement activation by PTM\u2010proteins may represent an underestimated contributor to chronic inflammation.<\/jats:p>","DOI":"10.1111\/imr.70166","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T12:18:28Z","timestamp":1789561108000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Complement Activation by Post\u2010Translationally Modified Proteins: Links to Chronic Inflammation and Autoimmunity"],"prefix":"10.1111","volume":"342","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2989-1631","authenticated-orcid":false,"given":"Marleen M. 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