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Archives of Pathology & Laboratory... Jan 2022Because granulomas are represented in almost every disease category, the number of clinically and pathologically important granulomatous pulmonary diseases is large.... (Review)
Review
CONTEXT.—
Because granulomas are represented in almost every disease category, the number of clinically and pathologically important granulomatous pulmonary diseases is large. Their diagnosis by pathologists is particularly challenging because of their nonspecificity. A specific diagnosis can be achieved only when a granuloma-inciting agent(s) (eg, acid-fast bacilli, fungi, foreign bodies, etc) are identified microscopically or by culture; this does not occur in most cases. Furthermore, a specific diagnosis cannot be reached in a high percentage of cases. Although sarcoidosis and infectious diseases account for approximately half of pulmonary granulomatous diseases worldwide, there is significant geographic variation in their prevalence.
OBJECTIVES.—
To present updated information to serve as a guide to pathologic diagnosis of pulmonary granulomatous diseases, to address some commonly held misconceptions and to stress the importance of multidisciplinary coordination. Presentation of basic aspects of granulomas is followed by discussion of specific disease entities, such as tuberculous and nontuberculous Mycobacterial infections, fungal, bacterial, and parasitic infections, sarcoidosis, necrotizing sarcoid granulomatosis, berylliosis, hypersensitivity pneumonitis, hot tub lung, rheumatoid nodule, bronchocentric granulomatosis, aspirated, inhaled, and embolized foreign bodies, drug-induced granulomas, chronic granulomatous disease, common variable immunodeficiency, and granulomatous lesions associated with various types of cancer.
DATA SOURCES.—
Review of pertinent medical literature using the PubMed search engine and the author's practical experience.
CONCLUSIONS.—
Although the diagnosis of granulomatous lung diseases continues to present significant challenges to pathologists, the information presented in this review can be helpful in overcoming them. The importance of multidisciplinary coordination in cases where morphologic diagnosis is not possible cannot be overstated.
Topics: Alveolitis, Extrinsic Allergic; Granuloma; Humans; Lung; Lung Diseases; Sarcoidosis
PubMed: 33905479
DOI: 10.5858/arpa.2020-0543-RA -
CMAJ : Canadian Medical Association... Feb 2024
Topics: Humans; Middle Aged; Berylliosis; Metal Workers
PubMed: 38346777
DOI: 10.1503/cmaj.221680-f -
Annals of the American Thoracic Society Apr 2018Metal-induced hypersensitivity is driven by T-cell sensitization to metal ions. Although numerous metals are associated with the development of diffuse parenchymal lung... (Review)
Review
Metal-induced hypersensitivity is driven by T-cell sensitization to metal ions. Although numerous metals are associated with the development of diffuse parenchymal lung disease, beryllium-induced hypersensitivity is the best-studied to date. This review focuses on the interaction between innate and adaptive immunity that leads to the development of chronic beryllium disease. After beryllium exposure, activation of the innate immune system occurs through the engagement of pattern-recognition receptors. This activation leads to cell death, release of alarmins, and activation and migration of dendritic cells to lung-draining lymph nodes. These events culminate in the development of an adaptive immune response that is characterized by beryllium-specific, T-helper type 1-polarized, CD4 T-cells and granuloma formation in the lung. The unique ability of beryllium to bind to human leukocyte antigen-DP molecules that express a glutamic acid at position 69 of the β-chain alters the charge and conformation of the human leukocyte antigen-DP-peptide complex. These changes induce post-translational modifications that are recognized as non-self. In essence, the ability of beryllium to create neoantigens underlies the genesis of chronic beryllium disease, and demonstrates the similarity between beryllium-induced hypersensitivity and autoimmunity.
Topics: Adaptive Immunity; Autoimmunity; Berylliosis; Beryllium; CD4-Positive T-Lymphocytes; Genetic Predisposition to Disease; HLA-DP beta-Chains; Humans; Hypersensitivity; Lung
PubMed: 29676647
DOI: 10.1513/AnnalsATS.201707-573MG -
Journal of Immunology (Baltimore, Md. :... Apr 2022Sarcoidosis and chronic beryllium disease are noninfectious lung diseases that are characterized by the presence of noncaseating granulomatous inflammation. Chronic... (Review)
Review
Sarcoidosis and chronic beryllium disease are noninfectious lung diseases that are characterized by the presence of noncaseating granulomatous inflammation. Chronic beryllium disease is caused by occupational exposure to beryllium containing particles, whereas the etiology of sarcoidosis is not known. Genetic susceptibility for both diseases is associated with particular MHC class II alleles, and CD4 T cells are implicated in their pathogenesis. The innate immune system plays a critical role in the initiation of pathogenic CD4 T cell responses as well as the transition to active lung disease and disease progression. In this review, we highlight recent insights into Ag recognition in chronic beryllium disease and sarcoidosis. In addition, we discuss the current understanding of the dynamic interactions between the innate and adaptive immune systems and their impact on disease pathogenesis.
Topics: Adaptive Immunity; Berylliosis; Beryllium; Chronic Disease; Granuloma; Humans; Lung Diseases; Sarcoidosis
PubMed: 35418504
DOI: 10.4049/jimmunol.2101159 -
Industrial Health 2016
Topics: Berylliosis; Construction Industry; Humans; Japan; Lead Poisoning; Lung Neoplasms; Metallurgy; Occupational Diseases; Occupational Exposure; Printing; Toluidines; Urinary Bladder Neoplasms
PubMed: 27020917
DOI: 10.2486/indhealth.54_201 -
Journal of Immunology (Baltimore, Md. :... Jan 2016Chronic beryllium (Be) disease is a granulomatous lung disorder that results from Be exposure in a genetically susceptible host. The disease is characterized by the... (Review)
Review
Chronic beryllium (Be) disease is a granulomatous lung disorder that results from Be exposure in a genetically susceptible host. The disease is characterized by the accumulation of Be-responsive CD4(+) T cells in the lung, and genetic susceptibility is primarily linked to HLA-DPB1 alleles possessing a glutamic acid at position 69 of the β-chain. Recent structural analysis of a Be-specific TCR interacting with a Be-loaded HLA-DP2-peptide complex revealed that Be is coordinated by amino acid residues derived from the HLA-DP2 β-chain and peptide and showed that the TCR does not directly interact with the Be(2+) cation. Rather, the TCR recognizes a modified HLA-DP2-peptide complex with charge and conformational changes. Collectively, these findings provide a structural basis for the development of this occupational lung disease through the ability of Be to induce posttranslational modifications in preexisting HLA-DP2-peptide complexes, resulting in the creation of neoantigens.
Topics: Berylliosis; Beryllium; CD4-Positive T-Lymphocytes; Genetic Predisposition to Disease; HLA-DP beta-Chains; Humans; Hypersensitivity; Lung; Protein Processing, Post-Translational; Receptors, Antigen, T-Cell
PubMed: 26685315
DOI: 10.4049/jimmunol.1502011 -
International Journal of Molecular... Nov 2022Cathepsin K (CatK) is a part of the family of cysteine proteases involved in many important processes, including the degradation activity of collagen 1 and elastin in... (Review)
Review
Cathepsin K (CatK) is a part of the family of cysteine proteases involved in many important processes, including the degradation activity of collagen 1 and elastin in bone resorption. Changes in levels of CatK are associated with various pathological conditions, primarily related to bone and cartilage degradation, such as pycnodysostosis (associated with CatK deficiency), osteoporosis, and osteoarthritis (associated with CatK overexpression). Recently, the increased secretion of CatK is being highly correlated to vascular inflammation, hypersensitivity pneumonitis, Wegener granulomatosis, berylliosis, tuberculosis, as well as with tumor progression. Due to the wide spectrum of diseases in which CatK is involved, the design and validation of active site-specific inhibitors has been a subject of keen interest in pharmaceutical companies in recent decades. In this review, we summarized the molecular background of CatK and its involvement in various diseases, as well as its clinical significance for diagnosis and therapy.
Topics: Cathepsin K; Collagen Type I; Bone and Bones; Cysteine Proteases
PubMed: 36430239
DOI: 10.3390/ijms232213762