Dataset Information

Immunohistochemical Detection of Propionibacterium acnes in the Retinal Granulomas in Patients with Ocular Sarcoidosis.

ABSTRACT: The etiology of sarcoidosis is still obscure; however, Mycobacteria and Propionibacterium acnes are considered the most implicated etiological agent for sarcoidosis. To investigate whether P. acnes is an etiological agent for sarcoid uveitis, we analyzed the frequency of P. acnes detected within the biopsied retinas from patients with ocular sarcoidosis by immunohistochemistry with a P. acnes-specific monoclonal antibody (PAB antibody). Eleven patients (12 eyes) with sarcoid uveitis were enrolled in this study. Eight patients with rhegmatogenous retinal detachment, two patients with non-sarcoid uveitis, and two patients with vitreoretinal lymphoma were enrolled as controls. In the sarcoidosis group, granulomas were mainly observed in the inner retinal layer filled with CD4+ cells and CD68+ cells, indicating the Th1 immune response. P. acnes, identified as round bodies that reacted with the PAB antibody, were present in 10/12 samples (83%) from 9/11 patients (82%) with sarcoidosis. These round bodies were scattered within the retinal granulomas mainly in the inner retinal layer. In the control group, no round bodies were detected. Our results suggested that P. acnes could be associated with sarcoid uveitis. We hypothesize that sarcoid granulomas may be formed by a Th1 immune response to P. acnes hematogenously transmitted to the retina.

SUBMITTER: Nagata K

PROVIDER: S-EPMC5680245 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Immunohistochemical Detection of Propionibacterium acnes in the Retinal Granulomas in Patients with Ocular Sarcoidosis.

Nagata Kenji K Eishi Yoshinobu Y Uchida Keisuke K Yoneda Kazuhito K Hatanaka Hiroki H Yasuhara Toru T Nagata Maho M Sotozono Chie C Kinoshita Shigeru S

Scientific reports 20171109 1

The etiology of sarcoidosis is still obscure; however, Mycobacteria and Propionibacterium acnes are considered the most implicated etiological agent for sarcoidosis. To investigate whether P. acnes is an etiological agent for sarcoid uveitis, we analyzed the frequency of P. acnes detected within the biopsied retinas from patients with ocular sarcoidosis by immunohistochemistry with a P. acnes-specific monoclonal antibody (PAB antibody). Eleven patients (12 eyes) with sarcoid uveitis were enrolle ...[more]

PMID: 29123243

Similar Datasets

Project description: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.

Project description:Propionibacterium acnes is thought to be a causative agent of sarcoidosis. Patients with sarcoidosis have circulating immune complexes. We attempted to detect P. acnes-derived immune complexes in sarcoid lesions.We evaluated formalin-fixed and paraffin-embedded lymph node samples from 38 sarcoidosis patients and 90 non-sarcoidosis patients (27 patients with necrotizing lymphadenitis, 28 patients with reactive lymphadenitis, 16 patients with colon cancer, 19 patients with gastric cancer) by immunohistochemistry using anti-human immunoglobulins (IgG, IgA, and IgM) and complement (C1q and C3c) antibodies, and a P. acnes-specific monoclonal antibody (PAB antibody) that reacts with the membrane-bound lipoteichoic acid of P. acnes.Small round bodies (SRBs) bound to IgA, IgM, or IgG were detected in sinus macrophages, in 32 (84%), 32 (84%), or 11 (29%) sarcoid samples, respectively, and in 19 (21%), 26 (29%), or no (0%) control samples, respectively. Some of these insoluble immune complexes (IICs) also bound to C1q and C3c. We developed a microwave treatment followed by brief trypsin digestion (MT treatment) to detect PAB-reactive SRBs bound to immunoglobulins (IIC-forming P. acnes). MT treatment revealed abundant IIC-forming P. acnes in most (89%) of the sarcoid samples and sparse distribution in some (20%) of the control samples with lymphadenitis, but no IIC-forming P. acnes was detected in control samples without inflammation. IIC-forming P. acnes were mostly bound to both IgA and IgM. The PAB-reactive antigen and immunoglobulins were both located at the peripheral rim of the IIC-forming P. acnes. Conventional electron microscopy identified many SRBs (0.5-2.0 ?m diameter) in sinus macrophages of sarcoid lymph nodes with many IIC-forming P. acnes, some of which were in phagolysosomes with a degraded and lamellar appearance.P. acnes-derived IICs in sinus macrophages were frequent and abundant in sarcoid lymph nodes, suggesting a potential etiologic link between sarcoidosis and this commensal bacterium.

Project description:The anaerobic gram-positive bacterium Propionibacterium acnes is a human skin commensal that is occasionally associated with inflammatory diseases. Recent work has indicated that evolutionary distinct lineages of P. acnes play etiologic roles in disease while others are associated with maintenance of skin homeostasis. To shed light on the molecular basis for differential strain properties, we carried out genomic and transcriptomic analysis of distinct P. acnes strains. We sequenced the genome of the P. acnes strain 266, a type I-1a strain. Comparative genome analysis of strain 266 and four other P. acnes strains revealed that overall genome plasticity is relatively low; however, a number of island-like genomic regions, encoding a variety of putative virulence-associated and fitness traits differ between phylotypes, as judged from PCR analysis of a collection of P. acnes strains. Comparative transcriptome analysis of strains KPA171202 (type I-2) and 266 during exponential growth revealed inter-strain differences in gene expression of transport systems and metabolic pathways. In addition, transcript levels of genes encoding possible virulence factors such as dermatan-sulphate adhesin, polyunsaturated fatty acid isomerase, iron acquisition protein HtaA and lipase GehA were upregulated in strain 266. We investigated differential gene expression during exponential and stationary growth phases. Genes encoding components of the energy-conserving respiratory chain as well as secreted and virulence-associated factors were transcribed during the exponential phase, while the stationary growth phase was characterized by upregulation of genes involved in stress responses and amino acid metabolism. Our data highlight the genomic basis for strain diversity and identify, for the first time, the actively transcribed part of the genome, underlining the important role growth status plays in the inflammation-inducing activity of P. acnes. We argue that the disease-causing potential of different P. acnes strains is not only determined by the phylotype-specific genome content but also by variable gene expression.

Dataset Information

Immunohistochemical Detection of Propionibacterium acnes in the Retinal Granulomas in Patients with Ocular Sarcoidosis.

Publications

Immunohistochemical Detection of Propionibacterium acnes in the Retinal Granulomas in Patients with Ocular Sarcoidosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets