Effects of weak/non-complement-binding HLA antibodies on C1q-binding
Hönger G, Amico P, Spriewald BM, Schaub S, Arnold M (2017)
Publication Type: Journal article
Publication year: 2017
Journal
Book Volume: 90
Pages Range: 88-94
Journal Issue: 2
DOI: 10.1111/tan.13062
Abstract
It is unknown under what conditions and to what extent weak/non-complement (C)-binding IgG subclasses (IgG2/IgG4) can block C1q-binding triggered by C-binding IgG subclasses (IgG1/IgG3). Therefore, we investigated in vitro C1q-binding induced by IgG subclass mixtures targeting the same HLA epitope. Various mixtures of HLA class II specific monoclonal antibodies of different IgG subclasses but identical V-region were incubated with HLA DRB1*07:01 beads and monitored for C1q-binding. The lowest concentration to achieve maximum C1q-binding was measured for IgG3, followed by IgG1, while IgG2 and IgG4 did not show appreciable C1q-binding. C1q-binding occurred only after a critical amount of IgG1/3 has bound and sharply increased thereafter. When both, C-binding and weak/non-C-binding IgG subclasses were mixed, C1q-binding was diminished proportionally to the fraction of IgG2/4. A 2- to 4-fold excess of IgG2/4 inhibited C1q-binding by 50%. Very high levels (10-fold excess) almost completely abrogated C1q-binding even in the presence of significant IgG1/3 levels that would usually lead to strong C1q-binding. In sensitized renal allograft recipients, IgG subclass constellations with >= 2-fold excess of IgG2/4 over IgG1/3 were present in 23/66 patients (34.8%) and overall revealed slightly decreased C1q signals. However, spiking of patient sera with IgG2 targeting a different epitope than the patient's IgG1/3 synergistically increased C1q-binding. In conclusion, if targeting the same epitope, an excess of IgG2/4 is repressing the extent of IgG1/3 triggered C1q-binding in vitro. Such IgG subclass constellations are present in about a third of sensitized patients and their net effect on C1q-binding is slightly inhibitory.
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APA:
Hönger, G., Amico, P., Spriewald, B.M., Schaub, S., & Arnold, M. (2017). Effects of weak/non-complement-binding HLA antibodies on C1q-binding. HLA, 90(2), 88-94. https://dx.doi.org/10.1111/tan.13062
MLA:
Hönger, G., et al. "Effects of weak/non-complement-binding HLA antibodies on C1q-binding." HLA 90.2 (2017): 88-94.
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