Neonatal Fc receptors may have ‘dual effect’ for mothers, infants in autoimmune disease
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SCOTTSDALE, Ariz. — A novel therapeutic approach targeting the neonatal fragment crystallizable receptor may have implications across a number of rheumatology disease states, according to a speaker.
“FcRn receptors are being tested in a large number of human diseases, including a lot of our diseases in rheumatology,” R. John Looney, MD, of the allergy, immunology and rheumatology division at the University of Rochester, told attendees at the Basic and Clinical Immunology for the Busy Clinician symposium.
The molecule may aid in maintaining concentrations of all IgG molecules in the peripheral blood and drive down various autoantibody levels, including anti-TT, anti-VZV, anti-Ro, anti-La and others, he added.
According to Looney, the FcRn agent efgartigimod (Vyvgart, Argenx) has gained FDA approval for myasthenia gravis, while trials for immune thrombocytopenia purpura have been completed. Meanwhile, patients are being recruited for trials of this agent in bullous pemphigoid and idiopathic inflammatory myopathy.
Another FcRn agent, rozanolixizumab (Rystiggo, UCB), has been granted FDA approval for myasthenia gravis, although trials for immune thrombocytopenia purpura were terminated. Patients are being recruited for a trial for myelin oligodendrocyte glycoprotein antibody disease.
Patients are also currently being enrolled in trials for nipocalimab (Johnson & Johnson), another FcRn agent, in myasthenia gravis and hemolytic disease of the fetus and newborn (HDFN).
“Interestingly there is a trial of these agents in fibromyalgia, which may raise a few eyebrows in our audience,” Looney said.
However, perhaps the most encouraging potential uses for the FcRn approach are in neonatal autoimmune diseases, including neonatal lupus, he added. According to Looney, these additionally include anti-Ro and anti-La antibody positivity, along with immune thrombocytopenic purpura and HDFN, which in turn includes anti-Rh and anti-Kell antibody positivity. In addition, the FcRn approach could be effective in targeting the anti-AChR antibodies implicated in Myasthenia gravis includes, he said.
“The message seems to be that this could work for a lot of neonatal autoimmune diseases,” Looney said.
However, he noted that many of the diseases are transient, indicating that therapeutics may not be necessary or warranted for all of them.
According to Looney, the key to the FcRn approach is that some of these agents can block maternal circulation of the pathogenic antibodies and prevent transfer to fetus.
“There is really a dual effect here,” he said.
Despite these encouraging findings, there is considerable work to be done, Looney added.
“There is a lot we do not know yet about these neonatal Fc receptors,” he said.
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Looney RJ. FcRN Inhibitors – A New Age in Immune-Based Therapeutics. Presented at Basic and Clinical Immunology for the Busy Clinician, Feb. 17-18, 2024; Scottsdale, Arizona (hybrid meeting).
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