title: Localization of propionibacterium acnes in granulomas supports a possible etiologic link between sarcoidosis and the bacterium.
abstract: Sarcoidosis likely results from the exposure of a genetically susceptible subject to an environmental agent, possibly an infectious one. Mycobacterial and propionibacterial organisms are the most commonly implicated potential etiologic agents. Propionibacterium acnes is the only microorganism, however, found in sarcoid lesions by bacterial culture. To evaluate the pathogenic role of this indigenous bacterium, we screened for the bacterium in sarcoid and non-sarcoid tissues using immunohistochemical methods with novel P. acnes-specific monoclonal antibodies that react with cell-membrane-bound lipoteichoic acid (PAB antibody) and ribosome-bound trigger-factor protein (TIG antibody). We examined formalin-fixed and paraffin-embedded samples of lungs and lymph nodes from 196 patients with sarcoidosis, and corresponding control samples from 275 patients with non-sarcoidosis diseases. The samples were mostly from Japanese patients, with 64 lymph node samples from German patients. Immunohistochemistry with PAB antibody revealed small round bodies within sarcoid granulomas in 20/27 (74%) video-assisted thoracic surgery lung samples, 24/50 (48%) transbronchial lung biopsy samples, 71/81 (88%) Japanese lymph node samples, and 34/38 (89%) German lymph node samples. PAB antibody did not react with non-sarcoid granulomas in any of the 45 tuberculosis samples or the 34 samples with sarcoid reaction. In nongranulomatous areas, small round bodies detected by PAB antibody were found in alveolar macrophages of lungs and paracortical macrophages of lymph nodes from many sarcoid and some non-sarcoid patients. Large-spheroidal acid-fast bodies, Hamazaki-Wesenberg bodies, which were found in 50% of sarcoid and 15% of non-sarcoid lymph node samples, reacted with both PAB and TIG antibodies. Electron microscopy revealed that these Hamazaki-Wesenberg bodies had a single bacterial structure and lacked a cell wall with occasional protrusions from the body. The high frequency and specificity of P. acnes, detected by PAB antibody within sarcoid granulomas, indicates that this indigenous bacterium might be the cause of granuloma formation in many sarcoid patients.
authors.affiliation: Department of Human Pathology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Negi
authors.forename: Tamiko
authors.initials: T
authors.lastname: Takemura
authors.forename: Josune
authors.initials: J
authors.lastname: Guzman
authors.forename: Keisuke
authors.initials: K
authors.lastname: Uchida
authors.forename: Asuka
authors.initials: A
authors.lastname: Furukawa
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Tadatsune
authors.initials: T
authors.lastname: Iida
authors.forename: Ikuo
authors.initials: I
authors.lastname: Ishige
authors.forename: Junko
authors.initials: J
authors.lastname: Minami
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yamada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawachi
authors.forename: Ulrich
authors.initials: U
authors.lastname: Costabel
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Eishi
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000096:biosynthesis; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology* / Q000473:pathology / Q000601:surgery; D006099:Granuloma / Q000382:microbiology* / Q000473:pathology / Q000601:surgery; D006801:Humans; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008198:Lymph Nodes / Q000382:microbiology* / Q000473:pathology; D010860:Pigments, Biological / Q000032:analysis; D011425:Propionibacterium acnes / Q000302:isolation & purification*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017565:Sarcoidosis, Pulmonary / Q000382:microbiology* / Q000473:pathology / Q000601:surgery
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D010860:Pigments, Biological