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Immune complex handling in transplantation: central roles for complement factor H, animal models, and translational implications.

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Τίτλος: Immune complex handling in transplantation: central roles for complement factor H, animal models, and translational implications.
Συγγραφείς: Quigg RJ; Department of Medicine, SUNY University at Buffalo, Jacobs School of Medicine & Biomedical Sciences, Buffalo, NY, United States., Alexander JJ; Department of Medicine, SUNY University at Buffalo, Jacobs School of Medicine & Biomedical Sciences, Buffalo, NY, United States.
Πηγή: Frontiers in immunology [Front Immunol] 2026 Jun 15; Vol. 17, pp. 1830799. Date of Electronic Publication: 2026 Jun 15 (Print Publication: 2026).
Τύπος έκδοσης: Journal Article; Review
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE
Imprint Name(s): Original Publication: [Lausanne : Frontiers Research Foundation]
Ιατρικοί όροι (MeSH): Complement Factor H*/immunology , Complement Factor H*/metabolism , Organ Transplantation*/adverse effects , Antigen-Antibody Complex*/immunology , Antigen-Antibody Complex*/metabolism , Graft Rejection*/immunology, Complement Activation/immunology ; Animals ; Humans ; Translational Research, Biomedical
Περίληψη: Immune complexes (ICs) are increasingly recognized as dynamic regulators of graft injury in solid organ transplantation. Beyond their formation, the biological impact of ICs is determined by how they are handled, trafficked, and cleared. Complement plays a central role in this process, functioning not only as an effector system but as a context-dependent regulator of IC fate. Classical pathway activation initiates complement deposition on ICs, while the alternative pathway amplifies these signals, with regulatory proteins constraining excessive activation. Complement factor H (CFH), the principal regulator of the alternative pathway, emerges as a key determinant of IC handling by modulating complement amplification and directing ICs toward non-inflammatory clearance pathways. This review integrates mechanistic insights into IC biology with clinical observations across kidney, heart, and lung transplantation. We highlight species-specific differences in IC clearance, examine how complement-targeted therapies intersect with IC biology, and address ongoing controversies regarding complement as a marker versus driver of injury. Collectively, these concepts position IC handling, not merely for IC formation, but as a central determinant of transplant outcomes.
(Copyright © 2026 Quigg and Alexander.)
Competing Interests: The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author JA declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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Contributed Indexing: Keywords: complement; factor H; immune complex; mouse model; transplant
Substance Nomenclature: 80295-65-4 (Complement Factor H)
0 (Antigen-Antibody Complex)
Entry Date(s): Date Created: 20260630 Date Completed: 20260630 Latest Revision: 20260813
Update Code: 20260814
PubMed Central ID: PMC13310762
DOI: 10.3389/fimmu.2026.1830799
PMID: 42375381
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1664-3224
DOI:10.3389/fimmu.2026.1830799