title: Association of natural anti-platelet factor 4/heparin antibodies with periodontal disease.
abstract: Platelet factor 4 (PF4) and heparin (H) form PF4/H complexes, the target of the immune reaction in heparin-induced thrombocytopenia (HIT). HIT seems to be a secondary immune response as anti-PF4/H-IgG antibodies occur as early as day 4 of heparin treatment. This study investigated whether prevalent infections such as periodontitis may induce the PF4/H immune response as: (1) natural anti-PF4/H Abs are present in the normal population; (2) PF4 bound to bacteria exposes the same antigen(s) as PF4/H complexes; and (3) sepsis induces PF4/H Abs in mice. We found PF4 bound to periodontal pathogens (Aggregatibacter actinomycetemcomitans; Porphyromonas gingivalis) enabling subsequent binding of human anti-PF4/H Abs. The association of natural PF4/H Abs and periodontitis was assessed in a case-control study, enrolling individuals with natural anti-PF4/H Abs (n = 40 matched pairs), and in the cross-sectional population-based Study of Health in Pomerania (SHIP; n = 3500). Both studies showed a robust association between periodontitis and presence of anti-PF4/H Abs independent of inflammation markers (case-control study: lowest vs highest tertile, odds ratio, 7.12 [95% confidence interval, 1.73-46.13; P = .005]; SHIP study, p(trend) ≤ 0.001). Thus, preimmunization to PF4/bacteria complexes by prevalent infections, for example, periodontitis, likely explains the presence of natural anti-PF4/heparin Abs and the early occurrence of anti-PF4/H-IgG in HIT.
authors.affiliation: Institut für Immunologie und Transfusionsmedizin, Ernst-Moritz-Arndt-Universität, Greifswald, Germany. greinach@uni-greifswald.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Greinacher
authors.forename: Birte
authors.initials: B
authors.lastname: Holtfreter
authors.forename: Krystin
authors.initials: K
authors.lastname: Krauel
authors.forename: Daniela
authors.initials: D
authors.lastname: Gätke
authors.forename: Claudia
authors.initials: C
authors.lastname: Weber
authors.forename: Till
authors.initials: T
authors.lastname: Ittermann
authors.forename: Sven
authors.initials: S
authors.lastname: Hammerschmidt
authors.forename: Thomas
authors.initials: T
authors.lastname: Kocher
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000906:Antibodies / Q000009:adverse effects* / Q000097:blood; D001327:Autoimmune Diseases / Q000097:blood / Q000453:epidemiology / Q000209:etiology / Q000276:immunology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005858:Germany / Q000453:epidemiology; D006493:Heparin / Q000276:immunology*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D010510:Periodontal Diseases / Q000097:blood / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D010978:Platelet Factor 4 / Q000276:immunology*; D016036:Seroepidemiologic Studies; D055815:Young Adult
chemical_list: D000906:Antibodies; D010978:Platelet Factor 4; D006493:Heparin