Perigranuloma Localization and Abnormal Maturation of B Cells

Kamphuis, Lieke; Zelm, Menno C. van; Lam, King H.; Rimmelzwaan, Guus F.; Baarsma, G.S.; Dik, Willem A.; Thio, Hok Bing; Daele, Paul La van; Velthoven, Mirjam E. van; Batstra, Manou R.; Hagen, P. Martin van; Laar, Jan A M van

doi:10.1164/rccm.201206-1024oc

Cited by 71 publications

(76 citation statements)

References 41 publications

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“…Typically, CD4-expressing Th cells are detected in and around the granulomas, whereas CD20-expressing B cells are found to accumulate around the granulomas. 118, 130 …”

Section: Figurementioning

confidence: 99%

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Immunopathogenesis of granulomas in chronic autoinflammatory diseases

et al. 2016

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Granulomas are clusters of immune cells. These structures can be formed in reaction to infection and display signs of necrosis, such as in tuberculosis. Alternatively, in several immune disorders, such as sarcoidosis, Crohn's disease and common variable immunodeficiency, non-caseating granulomas are formed without an obvious infectious trigger. Despite advances in our understanding of the human immune system, the pathogenesis underlying these non-caseating granulomas in chronic inflammatory diseases is still poorly understood. Here, we review the current knowledge about the immunopathogenesis of granulomas, and we discuss how the involved immune cells can be targeted with novel therapeutics.

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“…Typically, CD4-expressing Th cells are detected in and around the granulomas, whereas CD20-expressing B cells are found to accumulate around the granulomas. 118, 130 …”

Section: Figurementioning

confidence: 99%

“…B cells are rarely seen in granulomatous structures; however, they are abundantly present around granulomas. 118, 130 …”

Section: Figurementioning

confidence: 99%

Immunopathogenesis of granulomas in chronic autoinflammatory diseases

et al. 2016

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“…Processes underlying Th17 cell induction in sarcoidosis remain obscure, but the presence of these cells can suggest a role for autoimmune responses in sarcoidosis. B lymphocytes and plasma cells are found surrounding sarcoid granulomas (100). Additionally, active sarcoidosis patients have increased serum levels of B-cell-activating factor (BAFF) (101).…”

Section: Granuloma Formationmentioning

confidence: 99%

Granuloma Formation in Pulmonary Sarcoidosis

et al. 2013

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Sarcoidosis is a granulomatous disorder of unknown cause, affecting multiple organs, but mainly the lungs. The exact order of immunological events remains obscure. Reviewing current literature, combined with careful clinical observations, we propose a model for granuloma formation in pulmonary sarcoidosis. A tight collaboration between macrophages, dendritic cells, and lymphocyte subsets, initiates the first steps toward granuloma formation, orchestrated by cytokines and chemokines. In a substantial part of pulmonary sarcoidosis patients, granuloma formation becomes an on-going process, leading to debilitating disease, and sometimes death. The immunological response, determining granuloma sustainment is not well understood. An impaired immunosuppressive function of regulatory T cells has been suggested to contribute to the exaggerated response. Interestingly, therapeutical agents commonly used in sarcoidosis, such as glucocorticosteroids and anti-TNF agents, interfere with granuloma integrity and restore the immune homeostasis in autoimmune disorders. Increasing insight into their mechanisms of action may contribute to the search for new therapeutical targets in pulmonary sarcoidosis.

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“…Recent histological studies have discovered B-cell localization in the periphery of tissues of saroidosis patients [51,53,54]. Furthermore, increased naive and transitional systemic B cells in patients with active sarcoidosis have been observed compared with patients with inactive disease and healthy controls.…”

Section: New Discoveries and Potential Treatmentsmentioning

confidence: 99%

“…It is also notable that these same patients showed increased levels of IL-10 producing systemic B cells, as well as regulatory B cells involved in downregulating inflammation. Additionally, high levels of B-cell activating factor (BAFF), a phenotype typically associated with auto-immune diseases, was found in the serum of patients with active chronic sarcoidosis [51,54,55]. Not only is BAFF important for providing survival and maturation signals for B cells, but it has recently been shown to also participate in T-cell costimulation [56].…”

Section: New Discoveries and Potential Treatmentsmentioning

confidence: 99%

Targeting CD4 ⁺ T Cells for the Treatment of Sarcoidosis: a Promising Strategy?

Celada

Drake

2015

Immunotherapy

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Sarcoidois is an inflammatory disease of unknown origin characterized by the abnormal accumulation of noncaseating granulomas at sites of disease activity in multiple organs throughout the body with a predilection for the lungs. Because the exact trigger that leads to disease activity is still under investigation, current treatment options are contingent on the organ or organs affected. Corticosteroids are the therapy of choice, but antimalarials and TNF-α antagonists are also commonly prescribed. Recent findings provide evidence for the use of CD20 B-cell-depleting therapy as an alternative method of choice. However, because sarcoidosis is predominantly a T-helper cell-driven disorder, an overwhelming amount of compelling evidence exists for the use of CD4+ T-cell targeted therapy.

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Perigranuloma Localization and Abnormal Maturation of B Cells

Cited by 71 publications

References 41 publications

Immunopathogenesis of granulomas in chronic autoinflammatory diseases

Immunopathogenesis of granulomas in chronic autoinflammatory diseases

Granuloma Formation in Pulmonary Sarcoidosis

Targeting CD4 ⁺ T Cells for the Treatment of Sarcoidosis: a Promising Strategy?

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Perigranuloma Localization and Abnormal Maturation of B Cells

Cited by 71 publications

References 41 publications

Immunopathogenesis of granulomas in chronic autoinflammatory diseases

Immunopathogenesis of granulomas in chronic autoinflammatory diseases

Granuloma Formation in Pulmonary Sarcoidosis

Targeting CD4 + T Cells for the Treatment of Sarcoidosis: a Promising Strategy?

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Product

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Targeting CD4 ⁺ T Cells for the Treatment of Sarcoidosis: a Promising Strategy?