A new study demonstrated that naturally occurring antibodies targeting transthyretin (TTR) are present in the serum of both healthy individuals and patients with transthyretin amyloid cardiomyopathy (ATTR-CM). However, in patients with ATTR-CM, levels of naturally occurring antibodies against TTR were significantly altered compared with those of healthy controls.
The research, recently published in the journal Amyloid, analyzed antibody levels in blood samples from a diverse group, including healthy adults, newborns and patients with ATTR-CM who were either untreated or receiving the stabilizer medication tafamidis.
Naturally occurring antibodies have two main subtypes: IgG and IgM. Compared to healthy individuals, untreated patients with ATTR-CM had higher IgG levels and lower IgM levels. However, these trends changed in patients who took tafamidis.
Patients who took tafamidis for a year showed increases in both IgM and IgG antibody levels compared with before treatment. This increase was independent of the rise in total TTR levels, suggesting that the treatment affects antibodies independently, rather than simply being tied to the amount of protein circulating in the body.
The authors also found that IgM antibodies were present in the umbilical cord blood of newborns. Because IgM antibodies cannot pass from a mother to her baby during pregnancy, their presence at birth proves that they are a natural part of our innate immune system.
In the study, the antibodies against TTR demonstrated strong binding capabilities to both healthy TTR and the misfolded form seen in ATTR-CM. This binding occurred with high affinity, meaning the antibodies attach firmly to the TTR protein.
Further testing in a laboratory setting showed that these antibodies directly inhibit fibril formation. In patients with ATTR-CM, TTR proteins misfold and form into long, needle-like fibrils. By binding to unstable TTR proteins, the antibodies act as a barrier that prevents TTR from stacking into harmful deposits.
Although recent research into potential therapies has focused on “disease-reversing” mechanisms, in which synthetic antibodies stimulate the immune system to clear existing deposits, this study found that naturally occurring antibodies work differently.
While natural antibodies prevent new fibrils from forming, they showed no effect on the body’s ability to clear deposits. This suggests their primary role is protection and prevention rather than the active removal of existing deposits.
“These findings reveal an unrecognized immune mechanism with potential relevance for ATTR-CM pathogenesis and treatment,” researchers concluded. However, further research is needed to fully understand how these natural antibodies help maintain a healthy balance of TTR in the body and how they help prevent heart damage caused by protein clumping.
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