Disturbed Homeostasis and Multiple Signaling Defects in the Peripheral Blood B-Cell Compartment of Patients with Severe Chronic Sarcoidosis

Lee, Nam-Sihk; Barber, Laura; Akula, Shaw M.; Sigounas, George; Kataria, Yash P.; Arce, Sergio

doi:10.1128/cvi.05118-11

Cited by 53 publications

(58 citation statements)

References 65 publications

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“…In fact, some overlap with known loci for psoriasis and inflammatory bowel disease (7-9), findings consistent with the finding of multiple aberrations in adaptive immunity in patients with sarcoidosis (10)(11)(12). Others have previously demonstrated the significance of reduced levels of nuclear factor-kB (NF-kB)/P65 to sarcoidosis disease severity (12), as well as dysregulation within IL-12 and IL-23 pathways within cutaneous sarcoidosis specimens, using microarray analysis (13).…”

supporting

confidence: 60%

Solving the Conundrum: Immunogenetics of Sarcoidosis

Kaminski

Drake²

2015

Am J Respir Crit Care Med

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conducted during very brief periods (only 2 h of respiratory electrodialysis), and that further complications may arise when performing the technique over clinically meaningful periods. Moreover, the technical setup is complex and will need to be as safe as possible before it can be deployed in human trials. ConclusionsDuring the last decades, we have learned that the iatrogenic effects of invasive mechanical ventilation may negatively influence outcomes. Minimally invasive extracorporeal lung assist devices markedly reducing the need for alveolar ventilation would or could play a pivotal role in mitigating these negative influences.The innovative approach of Zanella and colleagues opens the possibility of ensuring sufficient CO 2 removal with a less-invasive way of using positive pressure ventilation than the current standard, or by eliminating invasive mechanical ventilation altogether. Doubling the amount of extracorporeal CO 2 removal would allow a considerable decrease in invasiveness by enabling lower flow rates and vascular access with smaller cannulae. Moreover, it offers the opportunity to widely apply and evaluate the concept of ultraprotective ventilation to reduce VILI, as well as a potential alternative to invasive mechanical ventilation for the support of hypercapnic respiratory failure. If the technique of Zanella and colleagues could be successfully transferred to the clinical setting, it might mark a quantum jump in the treatment of respiratory failure of different etiologies. n

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supporting

confidence: 60%

Solving the Conundrum: Immunogenetics of Sarcoidosis

Kaminski

Drake²

2015

Am J Respir Crit Care Med

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“…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%

“…Lee et al also found decreased expression of the costimulatory receptors CD19, CD20, CD21 and CD4, in addition to elevated expression of the coinhibitory receptors CD22, CD32, CD35, CD85J and CD152 by sarcoidosis systmic B cells compared with control cells. The sarcoidosis patients also exhibited a 65% reduction in the levels of NF-κB in peripheral systemic B cells [55]. …”

Section: New Discoveries and Potential Treatmentsmentioning

confidence: 99%

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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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“…Despite being a T-cell-mediated disease, some evidence suggests that B-cells may play a role in the pathogenesis of sarcoidosis [32]. Rituximab, a monoclonal antibody targeting B-cells, was recently tested in sarcoidosis [33].…”

Section: Biological Agentsmentioning

confidence: 99%