Jens Christian Jensenius

The human natural anti-αGal antibody targets common pathogens by broad-spectrum polyreactivity

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DOI

  • Jens Magnus Bernth Jensen, Orthopaedic Research Unit, Aarhus University Hospital, Aarhus N, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark; Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus N, Denmark.
  • ,
  • Sune Skeldal
  • Mikkel Steen Petersen, Orthopaedic Research Unit, Aarhus University Hospital, Aarhus N, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark; Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus N, Denmark.
  • ,
  • Bjarne Kuno Møller
  • Steen Hoffmann, Bacteria, Parasites and Fungi Department, Statens Serum Institute, Copenhagen, Denmark.
  • ,
  • Jens Christian Jensenius
  • Uffe B Skov Sørensen
  • Steffen Thiel

Naturally occurring antibodies are abundant in human plasma, but their importance in the defense against bacterial pathogens is unclear. We studied the role of the most abundant of such antibodies, the antibody against terminal galactose-α-1,3-galactose (anti-αGal), in the protection against pneumococcal infections (Streptococcus pneumonia). All known pneumococcal capsular polysaccharides lack terminal galactose-α-1,3-galactose, yet highly purified human anti-αGal antibody of the IgG class reacted with 48 of 91 pneumococcal serotypes. Anti-αGal was found to contain multiple antibody subsets that possess distinct specificities beyond their general reactivity with terminal galactose-α-1,3-galactose. These subsets in concert targeted a wide range of microbial polysaccharides. We found that anti-αGal constituted up to 40% of the total antibody reactivity to pneumococci in normal human plasma, that anti-αGal drives phagocytosis of pneumococci by human neutrophils, and that the anti-αGal level was 2-fold lower in patients prone to pneumococcal infections compared to controls. Moreover, during a 48-year period in Denmark, the 48 anti-αGal-reactive serotypes caused fewer invasive pneumococcal infections (n = 10,927) than the 43 non-reactive serotypes (n = 18,107), supporting protection on the population level. Our findings explain the broad-spectrum pathogen reactivity of anti-αGal and support that these naturally occurring polyreactive antibodies contribute significantly to human protective immunity.

Original languageEnglish
JournalImmunology
ISSN0019-2805
DOIs
Publication statusE-pub ahead of print - 19 Dec 2020

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