{"title":"Can sarcoidosis be cured?","authors":"Paolo Spagnolo, Marc A Judson","doi":"10.1016/j.coi.2025.102637","DOIUrl":"10.1016/j.coi.2025.102637","url":null,"abstract":"<p><p>Sarcoidosis is a systemic granulomatous disease of unknown cause that affects the lungs almost invariably. The clinical course and outcomes of pulmonary sarcoidosis are highly variable, ranging from mild and self-limiting to organ-threatening or life-threatening disease. Often, sarcoidosis remits permanently (spontaneously or following treatment), although disease resolution rates vary depending on demographic factors, mode of presentation, organs involved, and disease duration. Corticosteroids are the initial drugs of choice for the treatment of sarcoidosis. However, corticosteroid toxicity is common and causes significant morbidity and mortality; therefore, their use should be minimized. Certain phenotypes of sarcoidosis are more likely to undergo disease termination than others. In addition, certain pharmacologic maneuvers may be useful in terminating the disease, but these remain exploratory at this time. Future clinical and basic research of such phenotypes may lead to the discovery of immunopathogenic mechanisms involved in sarcoidosis disease termination.</p>","PeriodicalId":93967,"journal":{"name":"Current opinion in immunology","volume":"96 ","pages":"102637"},"PeriodicalIF":5.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Eliciting or silencing complement activation: strategies for optimizing monoclonal antibodies functions.","authors":"Axelle Amen, Nicole Thielens, Chantal Dumestre-Pérard, Giovanna Clavarino","doi":"10.1016/j.coi.2025.102638","DOIUrl":"10.1016/j.coi.2025.102638","url":null,"abstract":"<p><p>Tuning complement activity is essential to maximize therapeutic efficacy while minimizing off-target effects in monoclonal antibody (mAb) design. Complement-enhancing strategies are primarily applied to mAbs targeting pathogens, infected cells, tumors, or immunosuppressive cells within the tumor microenvironment. In contrast, complement-silencing strategies are more appropriate for mAbs used in autoimmune or inflammatory diseases, as well as in transplantation settings. This review highlights the symmetrical approaches available to either enhance or suppress complement activation: isotype or subtype selection, fragment crystallizable (Fc) region mutations, glycosylation engineering, and bispecific antibody design. These latter can either recruit C1q or block complement inhibitors to enhance activation or co-localize complement inhibitors. Additionally, Fc-deficient formats provide a straightforward way to eliminate complement-activating functions. As understanding of complement biology deepens and mAb engineering advances, especially with artificial intelligence-driven design, tailored modulation of complement activity will be central to next-generation mAb therapeutics.</p>","PeriodicalId":93967,"journal":{"name":"Current opinion in immunology","volume":"96 ","pages":"102638"},"PeriodicalIF":5.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144805439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}