Molecular signatures of intrarenal complement receptors C3AR1 and C5AR1 correlate with renal outcome in human lupus nephritis
Objective Lupus nephritis is one of the most common and serious complications of systemic lupus erythematosus (SLE). Lupus nephritis is a major cause of kidney failure in patients with SLE, attributed to increased morbidity and mortality. The in situ deposition of intrarenal immune complexes promote...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2022-09-01
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| Series: | Lupus Science and Medicine |
| Online Access: | https://lupus.bmj.com/content/9/1/e000831.full |
| _version_ | 1797787120965779456 |
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| author | Samy Hakroush Björn Tampe Desiree Tampe |
| author_facet | Samy Hakroush Björn Tampe Desiree Tampe |
| author_sort | Samy Hakroush |
| collection | DOAJ |
| description | Objective Lupus nephritis is one of the most common and serious complications of systemic lupus erythematosus (SLE). Lupus nephritis is a major cause of kidney failure in patients with SLE, attributed to increased morbidity and mortality. The in situ deposition of intrarenal immune complexes promotes the accumulation of inflammatory cells and causes kidney injury.Methods We here extracted transcriptome array datasets for expression of complement molecules in human lupus nephritis. Furthermore, we performed gene set enrichment analysis to identify molecular signatures associated with follow-up kidney function in lupus nephritis.Results Within the glomerular compartment, intrarenal mRNA expression levels of C3AR1 (p=0.0333) and C5AR1 (p=0.0167) correlated with treatment success reflected by kidney function recovery specifically in class III lupus nephritis, while no such association was observed in class II or class IV lupus nephritis. Interestingly, mRNA expression levels of either glomerular C3AR1 or C5AR1 resulted in identical gene set and signalling pathways enrichments in human lupus nephritis, including interferon signalling and signalling by interleukins. Direct comparison of C3AR1 and C5AR1 confirmed a strong association between glomerular mRNA expression levels of both complement receptors (r=0.8955, p<0.0001).Conclusions This study provides additional insights into signalling pathways associated with intrarenal synthesis of complement components in lupus nephritis that might be also affected by targeted therapy of the complement system. These results require confirmation but may contribute to a personalised treatment approach in distinct classes of human lupus nephritis. |
| first_indexed | 2024-03-13T01:17:32Z |
| format | Article |
| id | doaj.art-6ee99fafaa704d2c94dd5bda00b273f9 |
| institution | Directory Open Access Journal |
| issn | 2053-8790 |
| language | English |
| last_indexed | 2024-03-13T01:17:32Z |
| publishDate | 2022-09-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Lupus Science and Medicine |
| spelling | doaj.art-6ee99fafaa704d2c94dd5bda00b273f92023-07-05T08:30:06ZengBMJ Publishing GroupLupus Science and Medicine2053-87902022-09-019110.1136/lupus-2022-000831Molecular signatures of intrarenal complement receptors C3AR1 and C5AR1 correlate with renal outcome in human lupus nephritisSamy Hakroush0Björn Tampe1Desiree Tampe23 Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany4 Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany1 Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, GermanyObjective Lupus nephritis is one of the most common and serious complications of systemic lupus erythematosus (SLE). Lupus nephritis is a major cause of kidney failure in patients with SLE, attributed to increased morbidity and mortality. The in situ deposition of intrarenal immune complexes promotes the accumulation of inflammatory cells and causes kidney injury.Methods We here extracted transcriptome array datasets for expression of complement molecules in human lupus nephritis. Furthermore, we performed gene set enrichment analysis to identify molecular signatures associated with follow-up kidney function in lupus nephritis.Results Within the glomerular compartment, intrarenal mRNA expression levels of C3AR1 (p=0.0333) and C5AR1 (p=0.0167) correlated with treatment success reflected by kidney function recovery specifically in class III lupus nephritis, while no such association was observed in class II or class IV lupus nephritis. Interestingly, mRNA expression levels of either glomerular C3AR1 or C5AR1 resulted in identical gene set and signalling pathways enrichments in human lupus nephritis, including interferon signalling and signalling by interleukins. Direct comparison of C3AR1 and C5AR1 confirmed a strong association between glomerular mRNA expression levels of both complement receptors (r=0.8955, p<0.0001).Conclusions This study provides additional insights into signalling pathways associated with intrarenal synthesis of complement components in lupus nephritis that might be also affected by targeted therapy of the complement system. These results require confirmation but may contribute to a personalised treatment approach in distinct classes of human lupus nephritis.https://lupus.bmj.com/content/9/1/e000831.full |
| spellingShingle | Samy Hakroush Björn Tampe Desiree Tampe Molecular signatures of intrarenal complement receptors C3AR1 and C5AR1 correlate with renal outcome in human lupus nephritis Lupus Science and Medicine |
| title | Molecular signatures of intrarenal complement receptors C3AR1 and C5AR1 correlate with renal outcome in human lupus nephritis |
| title_full | Molecular signatures of intrarenal complement receptors C3AR1 and C5AR1 correlate with renal outcome in human lupus nephritis |
| title_fullStr | Molecular signatures of intrarenal complement receptors C3AR1 and C5AR1 correlate with renal outcome in human lupus nephritis |
| title_full_unstemmed | Molecular signatures of intrarenal complement receptors C3AR1 and C5AR1 correlate with renal outcome in human lupus nephritis |
| title_short | Molecular signatures of intrarenal complement receptors C3AR1 and C5AR1 correlate with renal outcome in human lupus nephritis |
| title_sort | molecular signatures of intrarenal complement receptors c3ar1 and c5ar1 correlate with renal outcome in human lupus nephritis |
| url | https://lupus.bmj.com/content/9/1/e000831.full |
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