A new genetic risk factor has been discovered for premature birth, say scientists at the University of California, San Diego School of Medicine.
The risk factor is related to a gene that codes for a protein that helps immune cells identify and attack group B Streptococcus (GBS) bacteria.
"Pregnant women are universally screened for these bacteria during pregnancy and administered antibiotics intravenously during labor if they test positive to protect the infant from infection," says co-author Dr. Victor Nizet, professor of pediatrics and pharmacy at San Diego School of Medicine.
"Our research may explain why some women and their infants are at higher risk of acquiring severe GBS infections than others," he adds.
GBS is found in the vagina or lower gastrointestinal tract of 15-20% of healthy women. However, this bacteria can cause dangerous, life-threatening infections - such as sepsis or meningitis - in premature babies.
Dr. Nizet and colleagues investigated two proteins that bind to GBS. But while one of these proteins, Siglec-14, activates the attack on the pathogen, the other, Siglec-5, suppresses immune response to the pathogen.
"We have one protein that tells the body to attack the pathogen and another that tells the body not to attack it," explains Raza Ali, PhD, the study's lead author. "Identifying the dual role of these receptors and how they are regulated may provide insight for future treatments against GBS."
By directing antimicrobial response without excessive inflammation, the researchers think these proteins together balance the body's immune response to pathogens.
Missing Siglec-14 protein implicated in premature birth risk
The researchers found that the attack-signaling protein, Siglec-14, is missing in some people, and fetuses that do not have this protein are more at risk of premature birth. The scientists think the premature birth risk could be increased because the immune response to GBS is imbalanced in the fetuses.
Study co-author Dr. Ajit Varki says:
"We found this association in GBS-positive but not GBS-negative pregnancies, highlighting the importance of GBS-siglec crosstalk on placental membranes."
The authors think that further research into the two siglec proteins could be useful in developing therapies against not only GBS, but also antibiotic-resistant infections, chronic diseases, HIV and blood clotting.
Scientists think the premature birth risk could be increased in fetuses lacking Siglec-14 because the immune response to GBS is imbalanced.
An interesting anomaly of GBS is that it is not found in any other animal except humans, including chimpanzees with whom we share 99% of our protein sequences.
"The expression of the two siglec proteins on the fetal membranes is also unique to humans," says Dr. Varki. "Our study offers intriguing insights into why certain bacterial pathogens may produce uniquely human diseases."
A 2006 study conducted by the Virginia Commonwealth University School of Medicine identified a genetic variant that the researchers suggested accounts for the higher rates of premature birth experienced by black women in the US, compared with white women.
The Virginia team found that a change in a single nucleotide in the SERPINH1 gene reduced the amount of collagen produced in the membranes that surround the fetus. As collagen lends strength to these membranes, its absence makes them more prone to rupturing. This genetic variant was found to be more common among people with African ancestry.