Site-Specific Analysis of Inflammatory Markers in Discoid Lupus Erythematosus Skin

Thorpe, Ryan; Gray, A. M. H.; Kumar, K. Shiva; Susa, Joseph; Chong, Benjamin F.

doi:10.1155/2014/925805

Cited by 17 publications

(11 citation statements)

References 37 publications

(48 reference statements)

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“…Primary sclerosing cholangitis is characterized by chronic bile duct destruction and inflammation and has been consistently associated with other liver and biliary tract cancers . Mechanisms for the associations with ankylosing spondylitis, aplastic anemia, celiac disease, discoid lupus erythematosus and vitiligo may include immunological, genetic and inflammatory pathways . For example, celiac disease, which causes inflammation in the small intestine, could potentially lead to carcinogenic changes in the ampulla of Vater, located in the duodenal wall.…”

Section: Discussionmentioning

confidence: 99%

Associations between autoimmune conditions and hepatobiliary cancer risk among elderly US adults

McGee

Castro

Engels

et al. 2018

Intl Journal of Cancer

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Growing evidence suggests that people with autoimmune conditions may be at increased risk of hepatobiliary tumors. In the present study, we evaluated associations between autoimmune conditions and hepatobiliary cancers among adults aged ≥66 in the United States. We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data (1992-2013) to conduct a population-based, case-control study. Cases (n = 32,443) had primary hepatobiliary cancer. Controls (n = 200,000) were randomly selected, cancer-free adults frequency-matched to cases by sex, age and year of selection. Using multivariable logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for associations with 39 autoimmune conditions identified via Medicare claims. We also conducted separate analyses for diagnoses obtained via inpatient versus outpatient claims. Sixteen conditions were associated with at least one hepatobiliary cancer. The strongest risk estimates were for primary biliary cholangitis with hepatocellular carcinoma (OR: 31.33 [95% CI: 23.63-41.56]) and primary sclerosing cholangitis with intrahepatic cholangiocarcinoma (7.53 [5.73-10.57]), extrahepatic cholangiocarcinoma (5.59 [4.03-7.75]), gallbladder cancer (2.06 [1.27-3.33]) and ampulla of Vater cancer (6.29 [4.29-9.22]). Associations with hepatobiliary-related conditions as a group were observed across nearly all cancer sites (ORs ranging from 4.53 [95% CI: 3.30-6.21] for extrahepatic cholangiocarcinoma to 7.18 [5.94-8.67] for hepatocellular carcinoma). Restricting to autoimmune conditions diagnosed via inpatient claims, 6 conditions remained associated with at least one hepatobiliary cancer, and several risk estimates increased. In the outpatient restricted analysis, 12 conditions remained associated. Multiple autoimmune conditions are associated with hepatobiliary cancer risk in the US Medicare population, supporting a shared immuno-inflammatory etiology to these cancers.

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Section: Discussionmentioning

confidence: 99%

Associations between autoimmune conditions and hepatobiliary cancer risk among elderly US adults

McGee

Castro

Engels

et al. 2018

Intl Journal of Cancer

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“…Further studies examining their interactions and impact on evolution of DLE will be planned. As DLE skin is enriched with multiple types of immune cells [ 13 , 46 ], our qRT-PCR data demonstrated that DLE skin upregulates cell surface markers expressed by dendritic cells (CD86) and monocytes (CD14), which can also express M1 macrophage-related proteins (e.g., CXCL10 [ 47 , 48 ] and ISG15 [ 49 ]).…”

Section: Discussionmentioning

confidence: 99%

A subset of CD163+ macrophages displays mixed polarizations in discoid lupus skin

et al. 2015

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IntroductionLesional skin of patients with discoid lupus erythematosus (DLE) contains macrophages, whose polarization has yet to be investigated. To test our hypothesis that M1 macrophages would be increased in DLE skin, we examined transcriptome alterations in immune cell gene expression and macrophage features in DLE and normal skin by using gene expression and histochemical approaches.MethodsGene expression of RNA from DLE lesional and normal control skin was compared by microarrays and quantitative real-time polymerase chain reaction (RT-PCR). Both skin groups were analyzed for CD163 expression by immunohistochemistry. Double immunofluorescence studies were performed to characterize protein expression of CD163+ macrophages.ResultsDLE skin had twice as many upregulated genes than downregulated genes compared with normal skin. Gene set enrichment analysis comparing differentially expressed genes in DLE and normal skin with previously published gene sets associated with M1 and M2 macrophages showed strong overlap between upregulated genes in DLE skin and M1 macrophages. Quantitative RT-PCR showed that several M1 macrophage-associated genes—e.g., chemokine (C-X-C motif) ligand 10 (CXCL10), chemokine (C-C motif) ligand 5 (CCL5), and signal transducer and activator of transcription 1 (STAT1)—had amplified mRNA levels in DLE skin. CD163+ macrophages were increased near the epidermal-dermal junction and perivascular areas in DLE skin compared with normal skin. However, double immunofluorescence studies of CD163+ macrophages revealed minor co-expression of M1 (CXCL10, tumor necrosis factor-alpha, and CD127) and M2 (CD209 and transforming growth factor-beta) macrophage-related proteins in DLE skin.ConclusionWhereas a subset of CD163+ macrophages displays mixed polarizations in DLE skin, other immune cells such as T cells can contribute to the expression of these macrophage-related genes.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0839-3) contains supplementary material, which is available to authorized users.

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“…Enhanced B cell infiltration appears to be accompanied by CD3 + , CD4 + , and CD8 + T cells (36). Moreover, B cells organize into aggregates, closely associated with CD3 + T cells (37). Nests of B cells and plasma cells in close proximity to T cells are also found in the lesional skin of patients with LE panniculitis (38) potential role of these lymphoid aggregates in cutaneous lupus has not been evaluated, and it is unknown if these structures produce antigen-specific B cells or pathogenic antibody (Figure 2).…”

Section: The Pathogenic Role Of Cutaneous B Cells In Human Diseasementioning

confidence: 98%

Human cutaneous B cells: what do we really know?

2021

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B cells play many critical roles in the systemic immune response, including antibody secretion, antigen presentation, T cell co-stimulation, and pro-and anti-inflammatory cytokine production. However, the contribution of B cells to the local immune response in many non-lymphoid tissues, such as the skin, is incompletely understood. Cutaneous B cells are scarce except in certain malignant and inflammatory conditions, and as such, have been poorly characterized until recently. Emerging evidence now suggests an important role for cutaneous B in both skin homeostasis and pathogenesis of skin disease. Herein, we discuss the potential mechanisms for cutaneous B cell recruitment, localized antibody production, and T cell interaction in human skin infections and primary skin malignancies (i.e., melanoma, squamous cell carcinoma). We further consider the likely contribution of cutaneous B cells to the pathogenesis of inflammatory skin diseases, including pemphigus vulgaris, lupus erythematosus, systemic sclerosis, hidradenitis suppurativa, and atopic dermatitis. Finally, we examine the feasibility of B cell targeted therapy in the dermatologic setting, emphasizing areas that are still open to investigation. Through this review, we hope to highlight what we really know about cutaneous B cells in human skin, which can sometimes be lost in reviews that more broadly incorporate extensive data from animal models.

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Site-Specific Analysis of Inflammatory Markers in Discoid Lupus Erythematosus Skin

Cited by 17 publications

References 37 publications

Associations between autoimmune conditions and hepatobiliary cancer risk among elderly US adults

Associations between autoimmune conditions and hepatobiliary cancer risk among elderly US adults

A subset of CD163+ macrophages displays mixed polarizations in discoid lupus skin

Human cutaneous B cells: what do we really know?

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