Exploiting the neonatal crystallizable fragment receptor to treat kidney disease

Dylewski, James F.; Haddad, George; Blaine, Judith

doi:10.1016/j.kint.2023.09.024

Cited by 4 publications

(1 citation statement)

References 97 publications

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“…Indeed, a significant number of clinical trials are currently underway for either optimizing FcRn-IgG interaction to reduce drug dosage and enhance treatment effectiveness or to block FcRn-autoantibody interactions. The various clinical trials are reviewed in [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Identification of Four Mouse FcRn Splice Variants and FcRn-Specific Vesicles

Haddad,

Blaine

2024

Cells

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Research into the neonatal Fc receptor (FcRn) has increased dramatically ever since Simister and Mostov first purified a rat version of the receptor. Over the years, FcRn has been shown to function not only as a receptor that transfers immunity from mother to fetus but also performs an array of different functions that include transport and recycling of immunoglobulins and albumin in the adult. Due to its important cellular roles, several clinical trials have been designed to either inhibit/enhance FcRn function or develop of non-invasive therapeutic delivery system such as fusion of drugs to IgG Fc or albumin to enhance delivery inside the cells. Here, we report the accidental identification of several FcRn alternatively spliced variants in both mouse and human cells. The four new mouse splice variants are capable of binding immunoglobulins’ Fc and Fab portions. In addition, we have identified FcRn-specific vesicles in which immunoglobulins and albumin can be stored and that are involved in the endosomal–lysosomal system. The complexity of FcRn functions offers significant potential to design and develop novel and targeted therapeutics.

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Section: Introductionmentioning

confidence: 99%

Identification of Four Mouse FcRn Splice Variants and FcRn-Specific Vesicles

Haddad,

Blaine

2024

Cells

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Current state and potential applications of neonatal Fc receptor (FcRn) inhibitors in hematologic conditions

Jacobs,

Booth,

Raza

et al. 2024

American J Hematol

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The neonatal fragment crystallizable (Fc) receptor (FcRn) transports IgG across mucosal surfaces and the placenta and protects IgG from degradation. Numerous clinical trials are investigating therapeutic FcRn inhibition for various immune‐mediated neuromuscular and rheumatologic conditions; however, FcRn inhibition also represents a potential therapy for IgG‐mediated hematologic conditions (e.g., immune thrombocytopenia, autoimmune hemolytic anemia, immune thrombotic thrombocytopenic purpura, acquired hemophilia, red blood cell/platelet alloimmunization). Current evidence derived from both in vitro and in vivo studies suggests that FcRn inhibitors effectively reduce total IgG levels without impacting its production or altering the levels of other immunoglobulin isotypes. Moreover, the risk of serious adverse events, including serious infections, appears to be lower than that seen with other commonly used immunomodulatory/immunosuppressive therapies, albeit in the setting of limited clinical trial data. Ultimately, additional clinical trials that include varied patient populations are required prior to incorporating these agents into standard treatment algorithms for most hematologic conditions. However, based on the pathophysiology of IgG‐mediated hematologic disorders and the mechanism of action of FcRn inhibitors, these agents may represent a future novel therapeutic strategy for patients with hematologic conditions caused by IgG antibodies.

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