Inflammation-based biomarkers for the prediction of nephritis in systemic lupus erythematosus

Inflammation-based biomarkers in renal lupus

Authors

Keywords:

lupus nephritis, inflammation, systemic lupus erythematosus

Abstract

Background/Aim: Inflammation is a crucial component in the pathophysiology of systemic lupus erythematosus (SLE) nephritis. Immune-based scores, such as the neutrophil-lymphocyte and the platelet-lymphocyte ratios (NLR and PLR, respectively) have been suggested as predictors of inflammation and prognosis in SLE. This study aimed to investigate the value of the systemic immune-inflammation index (SII), inflammatory prognostic index (IPI), and systemic inflammatory response index (SIRI) in SLE and lupus nephritis (LN).

Methods: This case-control study consisted of 108 newly diagnosed SLE patients (separated into two subgroups, which included 34 patients with biopsy-proven LN and 74 without nephritis) and 108 age- and gender-matched healthy controls who presented to our outpatient clinic between October 2015 and June 2020. Patients with malignancy, lymphoproliferative and hematologic disorders, active infection, and autoimmune diseases other than SLE were excluded. Inflammation-based biomarkers were calculated at the first presentation of the disease and before any medication was administered. SII was calculated as Neutrophil/Lymphocyte x Platelet, SIRI as Neutrophil x Monocyte/Lymphocyte, and IPI as CRP x NLR/serum albumin. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) was used to measure disease activity. The capability of SII, SIRI, NLR, PLR, and IPI to distinguish between SLE patients with or without nephritis was assessed using receiver operating characteristic (ROC) curves. Correlations of inflammation-based scores (SII, SIRI, IPI, NLR) with disease activity and laboratory data of SLE patients were analyzed.

Results: SII, SIRI, and IPI were significantly higher in SLE patients than in healthy controls (P=0.003, P=0.019, and P<0.001, respectively) and also significantly higher in patients with nephritis than in those without (P<0.001, P=0.009, and P=0.007, respectively). The area under the curve (AUC) for SII, SIRI, and IPI in terms of differentiating SLE patients with or without nephritis was 0.748, 0.690, and 0.663, respectively. The cut-off value of SII, SIRI, and IPI to predict LN was 552.25 (sensitivity: 64.7%; specificity: 64.9%; P<0.001), 1.08 (sensitivity: 61.8%; specificity: 62.2%; P=0.002), and 4.48 (sensitivity: 61.8%; specificity, 62.2%; P=0.007), respectively.

Conclusion: SII, SIRI, and IPI may be valuable and promising inflammation-based biomarkers in SLE and for the presence of nephritis in SLE patients. SII was found to be the most reliable predictor of SLE among the inflammation-based biomarkers in our study.

Downloads

Download data is not yet available.

References

D'Cruz DP. Systemic lupus erythematosus. BMJ. 2006;332(7546):890-4. doi: 10.1136/bmj.332.7546.890. DOI: https://doi.org/10.1136/bmj.332.7546.890

Gottschalk TA, Tsantikos E, Hibbs ML. Pathogenic Inflammation and Its Therapeutic Targeting in Systemic Lupus Erythematosus. Front Immunol. 2015;6:550. doi: 10.3389/fimmu.2015.00550. DOI: https://doi.org/10.3389/fimmu.2015.00550

Davidson A. What is damaging kidney in lupus nephritis? Nat Rev Rheumatol. 2016;12(3):143-53. doi: 10.1038/nrrheum.2015.159. DOI: https://doi.org/10.1038/nrrheum.2015.159

Liu CC, Ahearn JM. The search for lupus biomarkers. Best Pract Res Clin Rheumatol. 2009;23(4):507–23. doi: 10.1016/j.berh.2009.01.008. DOI: https://doi.org/10.1016/j.berh.2009.01.008

Littlejohn E, Marder W, Lewis E, Francis S, Jackish J, McCune WJ, et al. The ratio of erythrocyte sedimentation rate to C-reactive protein is useful in distinguishing infection from flare in systemic lupus erythematosus patients presenting with fever. Lupus. 2018;27(7):1123–9. doi: 10.1177/0961203318763732. DOI: https://doi.org/10.1177/0961203318763732

Lo MS, Zurakowski D, Son MB, Sundel RP. Hypergammaglobulinemia in the pediatric population as a marker for underlying autoimmune disease: a retrospective cohort study. Pediatr Rheumatol. 2013;11:42. doi: 10.1186/1546-0096-11-42. DOI: https://doi.org/10.1186/1546-0096-11-42

Hao X, Li D, Wu D, Zhang N. The Relationship between Hematological Indices and Autoimmune Rheumatic Diseases (ARDs), a Meta-Analysis. Sci Rep. 2017;7:10833. doi: 10.1038/s41598-017-11398-4. DOI: https://doi.org/10.1038/s41598-017-11398-4

Zhang Y, Lu JJ, Du YP, Feng CX, Wang LQ, Chen MB. Prognostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in gastric cancer. Medicine (Baltimore). 2018;97(12): e0144. doi: 10.1097/MD.0000000000010144. DOI: https://doi.org/10.1097/MD.0000000000010144

Hu B, Yang XR, Xu Y, Sun YF, Sun C, Guo W, et al. Systemic Immune-Inflammation Index Predicts Prognosis of Patients after Curative Resection for Hepatocellular Carcinoma. Clin Cancer Res. 2014;20(23):6212-22. doi: 10.1158/1078-0432.CCR-14-0442. DOI: https://doi.org/10.1158/1078-0432.CCR-14-0442

Zhong JH, Huang, DH, Chen ZY. Prognostic role of systemic immune-inflammation index in solid tumors: a systematic review and meta-analysis. Oncotarget. 2017;8(43):75381–8. doi: 10.18632/oncotarget.18856. DOI: https://doi.org/10.18632/oncotarget.18856

Dirican N, Dirican A, Anar C, Atalay S, Ozturk O, Bircan A, et al. A New Inflammatory Prognostic Index, Based on C-reactive Protein, the Neutrophil to Lymphocyte Ratio and Serum Albumin is Useful for Predicting Prognosis in Non-Small Cell Lung Cancer Cases. Asian Pac J Cancer Prev 2016;17(12):5101–5106. doi: 10.22034/APJCP.2016.17.12.5101

Gu L, Ma X, Wang L, Li H, Chen L, Li X, et al. Prognostic value of a systemic inflammatory response index in metastatic renal cell carcinoma and construction of a predictive model. 2016;8(32):52094-103. doi: 10.18632/oncotarget.10626 DOI: https://doi.org/10.18632/oncotarget.10626

Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677-86. doi:10.1002/art.34473. DOI: https://doi.org/10.1002/art.34473

Gladman DD, Ibañez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 2002;29(2):288–91.

Wu Y, Chen Y, Yang X, Chen L, Yang Y. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were associated with disease activity in patients with systemic lupus erythematosus. Int Immunopharmacol. 2016;36:94–9. doi: 10.1016/j.intimp.2016.04.006. DOI: https://doi.org/10.1016/j.intimp.2016.04.006

Lema GP, Maier H, Nieto E, Vielhauer V, Luckow B, Mampaso F, et al. Chemokine expression precedes inflammatory cell infiltration and chemokine receptor and cytokine expression during the initiation of murine lupus nephritis. JASN. 2001;12(7):1369–82. doi: 10.1681/ASN.V1271369. DOI: https://doi.org/10.1681/ASN.V1271369

Elkon KB, Stone VV. Type I interferon and systemic lupus erythematosus. J Interferon Cytokine Res. 2001;31(11):803–12. doi: 10.1089/jir.2011.0045. DOI: https://doi.org/10.1089/jir.2011.0045

Zahorec R. Ratio of neutrophil to lymphocyte counts rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy. 2001;102(1): 5-14.

Semple JW, Italiano JE Jr, Freedman J. Platelets and the immune continuum. Nat Rev Immunol. 2011;11(4):264–74. doi: 10.1038/nri2956. DOI: https://doi.org/10.1038/nri2956

Linge P, Fortin PR, Lood C, et al. The non-haemostatic role of platelets in systemic lupus erythematosus. Nat Rev Rheumatol. 2018;14(4):195–213. DOI: https://doi.org/10.1038/nrrheum.2018.38

Uslu AU, Küçük A, Şahin A, Ugan Y, Yılmaz R, Güngör T, et al. Two new inflammatory markers associated with Disease Activity Score-28 in patients with rheumatoid arthritis: neutrophil-lymphocyte ratio and platelet-lymphocyte ratio. Int J Rheum Dis. 2015;18(7):731–5. doi: 10.1111/1756-185X.12582. DOI: https://doi.org/10.1111/1756-185X.12582

Qin B, Ma N, Tang Q, Wei T, Yang M, Fu H, et al. Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were useful markers in assessment of inflammatory response and disease activity in SLE patients. Mod Rheumatol. 2016;26(3):372-6. doi: 10.3109/14397595.2015.1091136. DOI: https://doi.org/10.3109/14397595.2015.1091136

Yu H, Jiang L, Yao L, Gan C, Han X, Liu R, et al. Predictive value of the neutrophil-to-lymphocyte ratio and hemoglobin in systemic lupus erythematosus. Exp Ther Med. 2018;16(2):1547–53. doi: 10.3892/etm.2018.6309. DOI: https://doi.org/10.3892/etm.2018.6309

Wang L, Wang C, Jia X, Yang M, Yu J. Relationship between Neutrophil-to-Lymphocyte Ratio and Systemic Lupus Erythematosus: A Meta-analysis. Clinics. 2020;75:e1450. doi: 10.6061/clinics/2020/e1450. DOI: https://doi.org/10.6061/clinics/2020/e1450

Castrejón I, Tani C, Jolly M, Huang A, Mosca M. Indices to assess patients with systemic lupus erythematosus in clinical trials, long-term observational studies, and clinical care. Clin Exp Rheumatol. 2014;32(5):85-95.

Johnson RJ, Alpers CE, Pritzl P, Schulze M, Baker P, Pruchno C, et al. Platelets mediate neutrophil-dependent immune complex nephritis in the rat. J Clin Invest. 1988;82(4):1225–35. doi: 10.1172/JCI113720. DOI: https://doi.org/10.1172/JCI113720

Li L, Xia Y, Chen C, Cheng P, Peng C. Neutrophil-lymphocyte ratio in systemic lupus erythematosus disease: a retrospective study. Int J Clin Exp Med. 2015;8(7):11026-31.

Ayna AB, Ermurat S, Coşkun BN, Harman H, Pehlivan Y. Neutrophil to Lymphocyte Ratio and Mean Platelet Volume as Inflammatory Indicators in Systemic Lupus Erythematosus Nephritis. Arch Rheumatol. 2016;32(1):21-5. doi: 10.5606/ArchRheumatol.2017.5886. DOI: https://doi.org/10.5606/ArchRheumatol.2017.5886

Ozdemir A, Baran E, Kutu M, Celik S, Yılmaz M. Could systemic immune inflammation index be a new parameter for diagnosis and disease activity assessment in systemic lupus erythematosus? Int Urol Nephrol. 2023;55(1):211-6. doi: 10.1007/s11255-022-03320-3. DOI: https://doi.org/10.1007/s11255-022-03320-3

Downloads

Published

2023-05-15

Issue

Section

Research Article

How to Cite

1.
Orucoglu N. Inflammation-based biomarkers for the prediction of nephritis in systemic lupus erythematosus : Inflammation-based biomarkers in renal lupus. J Surg Med [Internet]. 2023 May 15 [cited 2024 Mar. 28];7(5):314-8. Available from: https://jsurgmed.com/article/view/7674