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We extended these observations by assessing the impact of a range of intrinsic factors on serum IgG subclass antibodies to both commensal and pathogenic oral bacteria that would contribute to variations in immune protection or disease susceptibility in periodontitis have not been described.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Subjects (<jats:italic>n<\/jats:italic>\u00a0=\u00a0278) were classified as healthy, gingivitis, or periodontitis and categorized as mild, moderate, and severe periodontitis. Demographic stratification included sex, age, race\/ethnicity, smoking, and obesity. Whole formalin\u2010fixed bacteria were used as antigens to detect serum immunoglobulin (Ig)G subclass antibody levels using an ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The greatest differences in variations in IgG subclasses occurred in periodontitis versus health or gingivitis to bacteria considered oral pathogens (eg, <jats:italic>Aggregatibacter actinomycetemcomitans<\/jats:italic>, <jats:italic>Porphyromonas gingivalis<\/jats:italic>, and <jats:italic>Treponema denticola<\/jats:italic>) with IgG1, IgG2, and IgG4 increased by three\u2010 to sevenfold with <jats:italic>Pg<\/jats:italic>. Differences in subclass levels and distribution were also observed related to disease severity, particularly related to individual subclass responses to <jats:italic>Pg<\/jats:italic>. Examination of the overall population showed that females had elevated antibody, reflected by elevated IgG2 amounts\/proportions. The older group of subjects demonstrated elevated antibody to multiple oral bacteria, lacking any particular subclass pattern. IgG2 antibody to <jats:italic>Aa<\/jats:italic> and <jats:italic>Pg<\/jats:italic> was increased in smokers. Multiple IgG subclass antibody levels to oral pathogens were significantly decreased in the obese subset within this population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This investigation identified patterns of IgG subclass antibody responses to oral bacteria and demonstrated substantial effects of disease impacting the level and subclass distribution of antibody to an array of oral bacteria. Altered subclass antibody profiles most often in IgG2 levels and for antibody to <jats:italic>P<\/jats:italic>. <jats:italic>gingivalis<\/jats:italic> were found related to sex, age, disease severity, race\/ethnicity, smoking, and obesity to both pathogens and commensal bacteria.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12882","type":"journal-article","created":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T13:22:21Z","timestamp":1617801741000},"page":"863-876","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Variations in IgG antibody subclass responses to oral bacteria: Effects of periodontal disease and modifying factors"],"prefix":"10.1111","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9743-6585","authenticated-orcid":false,"given":"Jeffrey L.","family":"Ebersole","sequence":"first","affiliation":[{"name":"Department of Biomedical Science School of Dental Medicine University of Nevada 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Dentistry University of Kentucky Lexington Kentucky USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"III","given":"Dolph","family":"Dawson","sequence":"additional","affiliation":[{"name":"Center for Oral Health Research College of Dentistry University of Kentucky Lexington Kentucky USA"},{"name":"Division of Periodontology College of Dentistry University of Kentucky Lexington Kentucky 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