Serum protein pattern associated with organ damage and lupus nephritis in systemic lupus erythematosus revealed by PEA immunoassay

Abstract Background Systemic lupus erythematosus (SLE) is a remarkably heterogeneous autoimmune disease. Despite tremendous efforts, our knowledge of serum protein patterns in severe SLE phenotypes is still limited. We investigated the serum protein pattern of SLE, with special emphasis on irreversi...

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Main Authors: Anna Petrackova, Andrea Smrzova, Petr Gajdos, Marketa Schubertova, Petra Schneiderova, Pavel Kromer, Vaclav Snasel, Martina Skacelova, Frantisek Mrazek, Josef Zadrazil, Pavel Horak, Eva Kriegova
Format: Article
Language:English
Published: BMC 2017-10-01
Series:Clinical Proteomics
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Online Access:http://link.springer.com/article/10.1186/s12014-017-9167-8
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author Anna Petrackova
Andrea Smrzova
Petr Gajdos
Marketa Schubertova
Petra Schneiderova
Pavel Kromer
Vaclav Snasel
Martina Skacelova
Frantisek Mrazek
Josef Zadrazil
Pavel Horak
Eva Kriegova
author_facet Anna Petrackova
Andrea Smrzova
Petr Gajdos
Marketa Schubertova
Petra Schneiderova
Pavel Kromer
Vaclav Snasel
Martina Skacelova
Frantisek Mrazek
Josef Zadrazil
Pavel Horak
Eva Kriegova
author_sort Anna Petrackova
collection DOAJ
description Abstract Background Systemic lupus erythematosus (SLE) is a remarkably heterogeneous autoimmune disease. Despite tremendous efforts, our knowledge of serum protein patterns in severe SLE phenotypes is still limited. We investigated the serum protein pattern of SLE, with special emphasis on irreversible organ damage and active lupus nephritis (LN) as assessed by renal Systemic Lupus Erythematosus Disease Activity Index. Methods We used proximity extension immunoassay (PEA, Proseek Multiplex, Olink) to assess the serum levels of ninety-two inflammation-related proteins in Czech patients with SLE (n = 75) and age-matched healthy control subjects (n = 23). Subgroup analysis was carried out on the basis of organ damage (with/without, 42/33) and biopsy-proven LN (with/without, 27/48; active LN, n = 13; inactive LN, n = 14). Results Of thirty deregulated proteins between SLE and the healthy controls (P corr  < 0.05), the top upregulated proteins in SLE were sirtuin 2, interleukin 18 (IL18), and caspase 8 (P corr  < 0.0006). Of these, sirtuin 2 and caspase 8 had not yet been reported with SLE. Elevated levels of IL8, CCL2/MCP1, CCL11, and MMP10 (P corr  < 0.05) were detected in patients with organ damage for which the serum levels of CCL11 and MMP10 were particularly informative in organ damage prediction. Comparing patients based on LN, elevated levels of CSF1, sIL15RA, sCD40, sCX3CL1, caspase 8, sIL18R1, bNGF, and GDNF (P corr  < 0.05) were detected in active LN. Except GDNF, all LN-associated markers showed usefulness in prediction of active renal disease. Conclusions This highly sensitive PEA analysis identified the serum pattern of SLE, organ damage, and active LN, with many novel candidate proteins detected. Their exact role and suitability as biomarkers in SLE deserve further investigation.
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spelling doaj.art-f2cd299f5d83405981961bc58eafaf812022-12-22T03:01:03ZengBMCClinical Proteomics1542-64161559-02752017-10-0114111510.1186/s12014-017-9167-8Serum protein pattern associated with organ damage and lupus nephritis in systemic lupus erythematosus revealed by PEA immunoassayAnna Petrackova0Andrea Smrzova1Petr Gajdos2Marketa Schubertova3Petra Schneiderova4Pavel Kromer5Vaclav Snasel6Martina Skacelova7Frantisek Mrazek8Josef Zadrazil9Pavel Horak10Eva Kriegova11Department of Immunology, Faculty of Medicine and Dentistry, Palacky UniversityDepartment of Internal Medicine III - Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, University Hospital, Palacky UniversityDepartment of Computer Science, Faculty of Electrical Engineering and Computer Science, Technical University of OstravaDepartment of Internal Medicine III - Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, University Hospital, Palacky UniversityDepartment of Immunology, Faculty of Medicine and Dentistry, Palacky UniversityDepartment of Computer Science, Faculty of Electrical Engineering and Computer Science, Technical University of OstravaDepartment of Computer Science, Faculty of Electrical Engineering and Computer Science, Technical University of OstravaDepartment of Internal Medicine III - Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, University Hospital, Palacky UniversityDepartment of Immunology, Faculty of Medicine and Dentistry, Palacky UniversityDepartment of Internal Medicine III - Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, University Hospital, Palacky UniversityDepartment of Internal Medicine III - Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, University Hospital, Palacky UniversityDepartment of Immunology, Faculty of Medicine and Dentistry, Palacky UniversityAbstract Background Systemic lupus erythematosus (SLE) is a remarkably heterogeneous autoimmune disease. Despite tremendous efforts, our knowledge of serum protein patterns in severe SLE phenotypes is still limited. We investigated the serum protein pattern of SLE, with special emphasis on irreversible organ damage and active lupus nephritis (LN) as assessed by renal Systemic Lupus Erythematosus Disease Activity Index. Methods We used proximity extension immunoassay (PEA, Proseek Multiplex, Olink) to assess the serum levels of ninety-two inflammation-related proteins in Czech patients with SLE (n = 75) and age-matched healthy control subjects (n = 23). Subgroup analysis was carried out on the basis of organ damage (with/without, 42/33) and biopsy-proven LN (with/without, 27/48; active LN, n = 13; inactive LN, n = 14). Results Of thirty deregulated proteins between SLE and the healthy controls (P corr  < 0.05), the top upregulated proteins in SLE were sirtuin 2, interleukin 18 (IL18), and caspase 8 (P corr  < 0.0006). Of these, sirtuin 2 and caspase 8 had not yet been reported with SLE. Elevated levels of IL8, CCL2/MCP1, CCL11, and MMP10 (P corr  < 0.05) were detected in patients with organ damage for which the serum levels of CCL11 and MMP10 were particularly informative in organ damage prediction. Comparing patients based on LN, elevated levels of CSF1, sIL15RA, sCD40, sCX3CL1, caspase 8, sIL18R1, bNGF, and GDNF (P corr  < 0.05) were detected in active LN. Except GDNF, all LN-associated markers showed usefulness in prediction of active renal disease. Conclusions This highly sensitive PEA analysis identified the serum pattern of SLE, organ damage, and active LN, with many novel candidate proteins detected. Their exact role and suitability as biomarkers in SLE deserve further investigation.http://link.springer.com/article/10.1186/s12014-017-9167-8Serum patternSystemic lupus erythematosusProximity extension immunoassayOrgan damageLupus nephritis
spellingShingle Anna Petrackova
Andrea Smrzova
Petr Gajdos
Marketa Schubertova
Petra Schneiderova
Pavel Kromer
Vaclav Snasel
Martina Skacelova
Frantisek Mrazek
Josef Zadrazil
Pavel Horak
Eva Kriegova
Serum protein pattern associated with organ damage and lupus nephritis in systemic lupus erythematosus revealed by PEA immunoassay
Clinical Proteomics
Serum pattern
Systemic lupus erythematosus
Proximity extension immunoassay
Organ damage
Lupus nephritis
title Serum protein pattern associated with organ damage and lupus nephritis in systemic lupus erythematosus revealed by PEA immunoassay
title_full Serum protein pattern associated with organ damage and lupus nephritis in systemic lupus erythematosus revealed by PEA immunoassay
title_fullStr Serum protein pattern associated with organ damage and lupus nephritis in systemic lupus erythematosus revealed by PEA immunoassay
title_full_unstemmed Serum protein pattern associated with organ damage and lupus nephritis in systemic lupus erythematosus revealed by PEA immunoassay
title_short Serum protein pattern associated with organ damage and lupus nephritis in systemic lupus erythematosus revealed by PEA immunoassay
title_sort serum protein pattern associated with organ damage and lupus nephritis in systemic lupus erythematosus revealed by pea immunoassay
topic Serum pattern
Systemic lupus erythematosus
Proximity extension immunoassay
Organ damage
Lupus nephritis
url http://link.springer.com/article/10.1186/s12014-017-9167-8
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