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.

Induction of Pulmonary Granuloma Formation byPropionibacterium acnesIs Regulated by MyD88 and Nox2

“…These granulomas are composed of multinucleated giant cells, macrophages, and lymphoid cells, and although the exact cause of sarcoidosis is unknown, it is thought to result from the combination of genetic susceptibility and exposure to a specific antigen, either environmental or infectious (1). Propionibacterium acnes has been implicated in the development of sarcoidosis because frequently it can be cultured out of the lymph nodes of patients with sarcoidosis (2) and it has been localized within sarcoidosis granulomas (3). In addition, P. acnes has been indicated as driving differential cytokine responses in the peripheral blood mononuclear cells of patients with sarcoidosis (4).…”

“…The anaerobic gram-positive P. acnes is the strongest bacterial candidate for a causative agent of sarcoidosis (10) because it is the only bacterium to be cultured from sarcoidosis lesions (2) and it has been localized within sarcoidosis granulomas (3). Previous models of sarcoid-like granuloma formation have been developed using heat-killed P. acnes; however, the use of heat to kill bacteria may denature bacterial surface proteins and runs the risk of generating an artificial immune response (11).…”

“…An antibody specific to P. acnes (PAB) was developed and produced as described previously (3). Both naive mice and mice 9 days after P. acnes administration were killed, and the lungs were removed.…”

Age-related differences in chest radiographic staging of sarcoidosis in Japan

“…From the results of molecular biological, pathological and epidemiological studies, it has been presumed that the antigen enters via the lungs during the early stage of the disease [6,7] and affects the regional intrathoracic lymph nodes. Likely carriers of the triggering antigen are mycobacteria and propionibacteria that act as intracellular parasites causing respiratory infection [8,9]. Dendritic cells, with the apparent ability to change from and to macrophages, are presumed to digest the antigen, migrate to the lymph node and induce antigen-specific Th1 cell proliferation [8,10].…”

Biological and chemical hazards in water-mix metalworking fluids and mists

“…Until recently, sarcoidosis was not considered an occupationally acquired disease. However, studies have shown that sarcoidosis can also be a result of antigen exposure (Eishi, 2013;Mariko et al, 2012).…”