Infliximab therapy modulates an antigen-specific immune response in chronic beryllium disease

Maier, Lisa A.; Barkes, Briana; Mroz, Margaret M.; Rossman, Milton D.; Barnard, Juliana; Gillespie, May; Martin, Allison K.; Mack, Douglas G.; Silveira, Lori; Sawyer, Richard T.; Newman, Lee S.; Fontenot, Andrew P.

doi:10.1016/j.rmed.2012.08.014

Cited by 15 publications

(11 citation statements)

References 29 publications

(28 reference statements)

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“…Treatment with infliximab has shown good responses in some patients with severe therapy-refractory sarcoidosis [[15], [16], [17]]. In CBD, infliximab treatment has shown effectiveness as well [18].…”

Section: Discussionmentioning

confidence: 99%

Sarcoidosis in a patient clinically diagnosed with silicosis; is silica associated sarcoidosis a new phenotype?

Beijer

Meek

Kromhout

et al. 2019

Respiratory Medicine Case Reports

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A diagnosis of silicosis is made on the basis of exposure and typical radiological findings, according to the ILO's International Classification of Radiographs of Pneumoconiosis. Radiological patterns of silicosis can, however, resemble sarcoidosis. Sarcoidosis is a multi-systemic disorder of unknown etiology, although a role for initiating inorganic triggers such as metals or silica has been suggested. In this case report, we illustrate a patient previously diagnosed with silicosis based on exposure and radiological features, progressive under immunosuppressive treatment. In view of these findings, an open lung biopsy was performed and revealed sarcoidosis. The patient was effectively treated with infliximab. Further analysis showed the presence of silica in the granulomas. Sensitization to silica was also demonstrated, suggesting an association between silica exposure and sarcoidosis in this patient.

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Section: Discussionmentioning

confidence: 99%

Sarcoidosis in a patient clinically diagnosed with silicosis; is silica associated sarcoidosis a new phenotype?

Beijer

Meek

Kromhout

et al. 2019

Respiratory Medicine Case Reports

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“…There has been one randomized clinical controlled trial of infliximab in CBD that was limited due to small numbers but demonstrated improvement in those with an abnormal DLCO at baseline. 141…”

Section: Treatmentmentioning

confidence: 99%

Sarcoidosis and Chronic Beryllium Disease: Similarities and Differences

Mayer

Hamzeh

Maier

2014

Semin Respir Crit Care Med

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Chronic beryllium disease (CBD) is a granulomatous lung disease that may be pathologically and clinically indistinguishable from pulmonary sarcoidosis, except through use of immunologic testing, such as the beryllium lymphocyte proliferation test (BeLPT). Similar to sarcoidosis, the pulmonary manifestations of CBD are variable and overlap with other respiratory diseases. Definitive diagnosis of CBD is established by evidence of immune sensitization to beryllium and diagnostic bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. However, the diagnosis of CBD can also be established on a medically probable basis in beryllium-exposed patients with consistent radiographic imaging and clinical course. Beryllium workers exposed too much higher levels of beryllium in the past demonstrated a much more fulminant disease than is usually seen today. Some extrapulmonary manifestations similar to sarcoidosis were noted in these historic cohorts, although with a narrower spectrum. Extrapulmonary manifestations of CBD are rare today. Since lung-predominant sarcoidosis can very closely resemble CBD, CBD is still misdiagnosed as sarcoidosis when current or past exposure to beryllium is not recognized and no BeLPT is obtained. This article describes the similarities and differences between CBD and sarcoidosis, including clinical and diagnostic features that can help physicians consider CBD in patients with apparent lung-predominant sarcoidosis.

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“…Once CBD CD4 + lung T-cells are activated, these cells clonally proliferate and secrete T-helper 1 (Th1)-type cytokines such as interleukin (IL)-2, interferon-γ and tumour necrosis factor (TNF)-α [6–8], which results in macrophage activation, accumulation, aggregation and the development of granulomatous inflammation [9]. Beryllium exposure stimulates a variety of cellular responses, including cell migration [10], cytokine regulation [11] and growth inhibition [12].…”

Section: Introductionmentioning

confidence: 99%

Beryllium-induced lung disease exhibits expression profiles similar to sarcoidosis

Silveira

Hamzeh

et al. 2016

Eur Respir J

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A subset of beryllium-exposed workers develop beryllium sensitisation (BeS) which precedes chronic beryllium disease (CBD). We conducted an in-depth analysis of differentially expressed candidate genes in CBD. We performed Affymetrix GeneChip 1.0 ST array analysis on peripheral blood mononuclear cells (PBMCs) from 10 CBD, 10 BeS and 10 beryllium-exposed, nondiseased controls stimulated with BeSO4 or medium. The differentially expressed genes were validated by high-throughput real-time PCR in this group and in an additional group of cases and nonexposed controls. The functional roles of the top candidate genes in CBD were assessed using a pharmacological inhibitor. CBD gene expression data were compared with whole blood and lung tissue in sarcoidosis from the Gene Expression Omnibus. We confirmed almost 450 genes that were significantly differentially expressed between CBD and controls. The top enrichment of genes was for JAK (Janus kinase)–STAT (signal transducer and activator of transcription) signalling. A JAK2 inhibitor significantly decreased tumour necrosis factor-α and interferon-γ production. Furthermore, we found 287 differentially expressed genes overlapped in CBD/sarcoidosis. The top shared pathways included cytokine–cytokine receptor interactions, and Toll-like receptor, chemokine and JAK–STAT signalling pathways. We show that PBMCs demonstrate differentially expressed gene profiles relevant to the immunnopathogenesis of CBD. CBD and sarcoidosis share similar differential expression of pathogenic genes and pathways.

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Infliximab therapy modulates an antigen-specific immune response in chronic beryllium disease

Cited by 15 publications

References 29 publications

Sarcoidosis in a patient clinically diagnosed with silicosis; is silica associated sarcoidosis a new phenotype?

Sarcoidosis in a patient clinically diagnosed with silicosis; is silica associated sarcoidosis a new phenotype?

Sarcoidosis and Chronic Beryllium Disease: Similarities and Differences

Beryllium-induced lung disease exhibits expression profiles similar to sarcoidosis

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