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Interleukin (IL) 16: a candidate urinary biomarker for proliferative lupus nephritis

OBJECTIVE: Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE). The pathogenesis is incompletely understood and diagnostic biomarkers are scarce. We investigated interleukin (IL) 16 as a potential biomarker for LN in a well-characterised cohort of patients with SLE....

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Autores principales: Häyry, Aliisa, Faustini, Francesca, Zickert, Agneta, Larsson, Anders, Niewold, Timothy B, Svenungsson, Elisabet, Oke, Vilija, Gunnarsson, Iva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476119/
https://www.ncbi.nlm.nih.gov/pubmed/36104119
http://dx.doi.org/10.1136/lupus-2022-000744
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author Häyry, Aliisa
Faustini, Francesca
Zickert, Agneta
Larsson, Anders
Niewold, Timothy B
Svenungsson, Elisabet
Oke, Vilija
Gunnarsson, Iva
author_facet Häyry, Aliisa
Faustini, Francesca
Zickert, Agneta
Larsson, Anders
Niewold, Timothy B
Svenungsson, Elisabet
Oke, Vilija
Gunnarsson, Iva
author_sort Häyry, Aliisa
collection PubMed
description OBJECTIVE: Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE). The pathogenesis is incompletely understood and diagnostic biomarkers are scarce. We investigated interleukin (IL) 16 as a potential biomarker for LN in a well-characterised cohort of patients with SLE. METHODS: We measured urinary (u-) and plasma (p-) levels of IL-16 in predefined patient groups using ELISA: LN (n=84), active non-renal SLE (n=63), inactive non-renal SLE (n=73) and matched population controls (n=48). The LN group included patients with recent biopsy-confirmed proliferative (PLN, n=47), mesangioproliferative (MES, n=11) and membranous (MLN, n=26) LN. Renal expression of IL-16 was investigated by immunohistochemistry. Associations between IL-16 measurements and clinical parameters and the diagnostic value for LN were explored. RESULTS: p-IL-16 was detected in all investigated cases and high p-IL-16 levels were observed in patients with active SLE. u-IL-16 was detected (dt-u-IL-16) in 47.6% of patients with LN, while only up to 17.8% had dt-u-IL-16 in other groups. In the LN group, 68% of patients with PLN had dt-u-IL-16, while the proportions in the MLN and MES groups were lower (11.5% and 45.5%, respectively). The highest u-IL-16 levels were detected in the PLN group. In the regression model, u-IL-16 levels differentiated PLN from other LN patient subgroups (area under the curve 0.775–0.896, p<0.0001). dt-u-IL-16 had superior specificity but slightly lower sensitivity than elevated anti-double-stranded DNA and low complement C3 or C4 in diagnosing PLN. A high proportion of LN kidney infiltrating cells expressed IL-16. CONCLUSIONS: We demonstrate that detectable u-IL-16 can differentiate patients with PLN from those with less severe LN subtypes and active non-renal SLE. Our findings suggest that u-IL-16 could be used as a screening tool at suspicion of severe LN. Furthermore, the high IL-16 levels in plasma, urine and kidney tissue imply that IL-16 could be explored as a therapeutic target in SLE.
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spelling pubmed-94761192022-09-16 Interleukin (IL) 16: a candidate urinary biomarker for proliferative lupus nephritis Häyry, Aliisa Faustini, Francesca Zickert, Agneta Larsson, Anders Niewold, Timothy B Svenungsson, Elisabet Oke, Vilija Gunnarsson, Iva Lupus Sci Med Lupus Nephritis OBJECTIVE: Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE). The pathogenesis is incompletely understood and diagnostic biomarkers are scarce. We investigated interleukin (IL) 16 as a potential biomarker for LN in a well-characterised cohort of patients with SLE. METHODS: We measured urinary (u-) and plasma (p-) levels of IL-16 in predefined patient groups using ELISA: LN (n=84), active non-renal SLE (n=63), inactive non-renal SLE (n=73) and matched population controls (n=48). The LN group included patients with recent biopsy-confirmed proliferative (PLN, n=47), mesangioproliferative (MES, n=11) and membranous (MLN, n=26) LN. Renal expression of IL-16 was investigated by immunohistochemistry. Associations between IL-16 measurements and clinical parameters and the diagnostic value for LN were explored. RESULTS: p-IL-16 was detected in all investigated cases and high p-IL-16 levels were observed in patients with active SLE. u-IL-16 was detected (dt-u-IL-16) in 47.6% of patients with LN, while only up to 17.8% had dt-u-IL-16 in other groups. In the LN group, 68% of patients with PLN had dt-u-IL-16, while the proportions in the MLN and MES groups were lower (11.5% and 45.5%, respectively). The highest u-IL-16 levels were detected in the PLN group. In the regression model, u-IL-16 levels differentiated PLN from other LN patient subgroups (area under the curve 0.775–0.896, p<0.0001). dt-u-IL-16 had superior specificity but slightly lower sensitivity than elevated anti-double-stranded DNA and low complement C3 or C4 in diagnosing PLN. A high proportion of LN kidney infiltrating cells expressed IL-16. CONCLUSIONS: We demonstrate that detectable u-IL-16 can differentiate patients with PLN from those with less severe LN subtypes and active non-renal SLE. Our findings suggest that u-IL-16 could be used as a screening tool at suspicion of severe LN. Furthermore, the high IL-16 levels in plasma, urine and kidney tissue imply that IL-16 could be explored as a therapeutic target in SLE. BMJ Publishing Group 2022-09-14 /pmc/articles/PMC9476119/ /pubmed/36104119 http://dx.doi.org/10.1136/lupus-2022-000744 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Lupus Nephritis
Häyry, Aliisa
Faustini, Francesca
Zickert, Agneta
Larsson, Anders
Niewold, Timothy B
Svenungsson, Elisabet
Oke, Vilija
Gunnarsson, Iva
Interleukin (IL) 16: a candidate urinary biomarker for proliferative lupus nephritis
title Interleukin (IL) 16: a candidate urinary biomarker for proliferative lupus nephritis
title_full Interleukin (IL) 16: a candidate urinary biomarker for proliferative lupus nephritis
title_fullStr Interleukin (IL) 16: a candidate urinary biomarker for proliferative lupus nephritis
title_full_unstemmed Interleukin (IL) 16: a candidate urinary biomarker for proliferative lupus nephritis
title_short Interleukin (IL) 16: a candidate urinary biomarker for proliferative lupus nephritis
title_sort interleukin (il) 16: a candidate urinary biomarker for proliferative lupus nephritis
topic Lupus Nephritis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476119/
https://www.ncbi.nlm.nih.gov/pubmed/36104119
http://dx.doi.org/10.1136/lupus-2022-000744
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