Targeting the neonatal Fc receptor (FcRn) may be a promising avenue for treating numerous diseases, including fetal and neonatal alloimmune thrombocytopenia (FNAIT), according to a review recently published in the New England Journal of Medicine.
FNAIT arises when the maternal and fetal platelet antigens are incompatible, often due to the paternal platelet antigens inherited by the fetus. In response, the mother produces immunoglobulin G (IgG) antibodies and transports them across the placenta via FcRn. Once in the fetal circulation, these maternal IgG antibodies attack the fetal platelets, causing thrombocytopenia.
In addition to acting as a transporter, FcRn prevents the breakdown of IgG and plays a role in regulating immune responses. Given its wide range of functions, FcRn has been implicated in many diseases, including central nervous system disorders, skin conditions, rheumatologic diseases and more.
“Understanding the biologic features of FcRn has enabled the development of therapeutics that block FcRn–IgG interactions to disrupt placental transport of IgG, cause IgG degradation, and decrease activation of cellular immunity,” the study authors explained.
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Many strategies are being investigated to block FcRn-IgG interactions, including the development of drugs that bind to FcRn and thereby prevent IgG from binding. Researchers are also studying enzymes that break down IgG to inhibit the FcRn-IgG interaction.
Anti-FcRn drugs are considered to be relatively safe, the authors stated, with the most commonly reported adverse effect being headaches. Some individuals may also experience diminished albumin levels.
Several clinical trials are currently being conducted to evaluate the safety and efficacy of FcRn inhibition in diseases such as myasthenia gravis, immune thrombocytopenic purpura (ITP) and hemolytic disease of the fetus and newborn (HDFN). Although many of these trials have seen positive results, the authors noted that levels of patient response may vary between diseases, highlighting the need for further research.
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