IgM Antibodies Offer Protection Against Staph Infections

One of the main sources of community- and hospital-acquired infections is Staphylococcus aureus, well known for its antibiotic-resistant variation Methicillin-resistant Staphylococcus aureus (MRSA). The most recent data indicates that approximately 120,000 people worldwide died from MRSA in 2022, and many more were killed by S. aureus strains that are sensitive to antibiotics.

However, all efforts to create a vaccine that protects against S. aureus have failed thus far. Researchers from Amsterdam UMC have identified a critical immunological component that protects against infection, pointing to a new avenue for research in conjunction with UMC Utrecht, Leiden University, and the University of California, San Diego. Cell Reports Medicine published these findings.

Our findings directly challenge the current way of thinking about staphylococcal infections. It is generally assumed that the recognition of S. aureus by IgG antibodies, which help immune cells to kill Staph, is key to offering protection. In this study, we propose that this might not be the answer. We show that not IgG, but IgM antibodies are required for clearance of S. aureus during an infection.”

Nina van Sorge, Professor, Translational Microbiology, University of California San Diego

The research team investigated the existence of S. aureus-recognizing antibodies in the blood of healthy people under the direction of Professor van Sorge and Dr. Astrid Hendriks, a postdoc in her lab.

They concentrate on certain sugars that surround the bacterium like a sugar coat. It was shown that nearly every healthy person has both IgG and IgM antibodies that were capable of identifying these sugar coatings.

We all have high antibody levels against the S. aureus sugar coat, since we are exposed to this bacterium multiple times throughout our lives without getting ill. Yet we do not know which antibodies are in fact preventing us from getting ill.”

Dr. Astrid Hendriks, University of California San Diego

IgM antibodies greatly outperformed IgG antibodies in the lab at killing the bacteria.

IgG antibodies offer protection against bacterial pathogens in general and are actually critical for the protective effect of vaccines against for example pneumococcal and meningococcal infections. But for S. aureus, it is more complex. This clever bacterium has developed ways to circumvent our defense system, and in particular IgG antibodies, which is part of the reason that it still causes so many problems.”

Nina van Sorge, Professor, Translational Microbiology, University of California San Diego

S. aureus, the researchers discovered, did not mitigate the effects of IgM.

Ultimately, they found that compared to healthy people, patients with potentially fatal S. aureus bloodstream infections had significantly lower blood levels of IgM antibodies specific to the sugar coat.

Notably, the individuals with the lowest levels of IgM antibodies were those who did not survive the infection. The researchers speculate that low levels of IgM antibodies specific to sugars raise the risk of fatal staphylococcal infections and other serious diseases.

These results offer significant new insights that could influence the development of vaccines and other immune-boosting treatments in the future, even if further study is required to confirm this theory.