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001-es BibID:	BIBFORM103050
035-os BibID:	(WOS)000758481100007 (Scopus)85124266369
Első szerző:	Amendt, Timm
Cím:	Autoreactive antibodies control blood glucose by regulating insulin homeostasis / Timm Amendt, Gabriele Allies, Antonella Nicolo, Omar El Ayoubi, Marc Young, Tamás Röszer, Corinna S. Setz, Klaus Warnatz, Hassan Jumaa
Dátum:	2022
ISSN:	0027-8424 1091-6490
Megjegyzések:	Homeostasis of metabolism by hormone production is crucial for maintaining physiological integrity, as disbalance can cause severe metabolic disorders such as diabetes mellitus. Here, we show that antibody-deficient mice and immunodeficiency patients have sub-physiological blood glucose concentrations. Restoring blood glucose physiology required total IgG injections and insulin-specific IgG antibodies detected in total IgG preparations and in the serum of healthy individuals. In addition to the insulin-neutralizing antiinsulin IgG, we identified two fractions of anti-insulin IgM in the serum of healthy individuals. These autoreactive IgM fractions differ in their affinity to insulin. Interestingly, the low-affinity IgM fraction (anti-insulin IgMlow) neutralizes insulin and leads to increased blood glucose, whereas the high-affinity IgM fraction (anti-insulin IgMhigh) protects insulin from neutralization by anti-insulin IgG, thereby preventing blood glucose dysregulation. To demonstrate that anti-insulin IgMhigh acts as a protector of insulin and counteracts insulin neutralization by anti-insulin IgG, we expressed the variable regions of a high-affinity anti-insulin antibody as IgG and IgM. Remarkably, the recombinant anti-insulin IgMhigh normalized insulin function and prevented IgG-mediated insulin neutralization. These results suggest that autoreactive antibodies recognizing insulin are key regulators of blood glucose and metabolism, as they control the concentration of insulin in the blood. Moreover, our data suggest that preventing autoimmune damage and maintaining physiological homeostasis requires adaptive tolerance mechanisms generating high-affinity autoreactive IgM antibodies during memory responses.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk autoimmunity IgM IgG aging B cells
Megjelenés:	Proceedings Of The National Academy Of Sciences Of The United States Of America. - 119 : 6 (2022), p. 1-10. -
További szerzők:	Allies, Gabriele Nicolo, Antonella El Ayoubi, Omar Young, Marc Röszer Tamás (1979-) (orvos, biológus) Setz, Corinna Warnatz, Klaus Jumaa, Hassan
Pályázati támogatás:	German Research Foundation (DFG) TRR130 Egyéb German Research Foundation (DFG) SFB1074 Egyéb German Research Foundation (DFG) SFB 1279 Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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