Salivary IgA from the sublingual compartment as a novel noninvasive proxy for intestinal immune induction.
Whole-saliva IgA appears like an attractive noninvasive readout for intestinal immune induction after enteric infection or vaccination, but has failed to show consistent correlation with established invasive markers and IgA in feces or intestinal lavage. For reference, we measured antibodies in samples from 30 healthy volunteers who were orally infected with wild-type enterotoxigenic Escherichia coli. The response against these bacteria in serum, lavage, and lymphocyte supernatants (antibody-in-lymphocyte-supernatant, ALS) was compared with that in targeted parotid and sublingual/submandibular secretions. Strong correlation occurred between IgA antibody levels against the challenge bacteria in sublingual/submandibular secretions and in lavage (r=0.69, P<0.0001) and ALS (r=0.70, P<0.0001). In sublingual/submandibular secretions, 93% responded with more than a twofold increase in IgA antibodies against the challenge strain, whereas the corresponding response in parotid secretions was only 67% (P=0.039). With >twofold ALS as a reference, the sensitivity of a >twofold response for IgA in sublingual/submandibular secretion was 96%, whereas it was only 67% in the parotid fluid. To exclude that flow rate variations influenced the results, we used albumin as a marker. Our data suggested that IgA in sublingual/submandibular secretions, rather than whole saliva with its variable content of parotid fluid, is a preferential noninvasive proxy for intestinal immune induction.
Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway.
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Aase
Center for Intervention Science in Maternal and Child Health and Centre for International health, Centre for International Health, University of Bergen, Bergen, Norway.|Department of International Public Health, Norwegian Institute of Public Health, Oslo, Norway.
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Sommerfelt
Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway.
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Petersen
Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway.
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Bolstad
Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Research and Development, Haukeland University Hospital, Bergen, Norway.
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Cox
Department of Clinical Science, University of Bergen, Bergen, Norway.|Division for Infectious Disease, Department of Medicine, Haukeland University Hospital, Bergen, Norway.
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Langeland
Department of Anesthesia and Intensive Care, Haukeland University Hospital, Bergen, Norway.|Department of Clinical Medicine, University of Bergen, Bergen, Norway.
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Guttormsen
Center for Intervention Science in Maternal and Child Health and Centre for International health, Centre for International Health, University of Bergen, Bergen, Norway.|Department of Biomedicine, University of Bergen, Bergen, Norway.
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Steinsland
Department of Clinical Science, University of Bergen, Bergen, Norway.|Division for Infectious Disease, Department of Medicine, Haukeland University Hospital, Bergen, Norway.
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Skrede
LIIPAT, Centre for Immune Regulation, University of Oslo, Oslo, Norway.|Department of Pathology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
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Brandtzaeg
D000907:Antibodies, Bacterial / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D054307:Enterotoxigenic Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000175:diagnosis / Q000276:immunology*; D005243:Feces; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000378:metabolism*; D007422:Intestines / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D010306:Parotid Gland / Q000378:metabolism*; D012463:Saliva / Q000378:metabolism*; D012680:Sensitivity and Specificity
D000907:Antibodies, Bacterial; D015415:Biomarkers; D017077:Culture Media, Conditioned; D007070:Immunoglobulin A