During the last decades, there has been an increased interest in the discovery and validation of biomarkers that reliably reflect specific aspects of lupus. Although many biomarkers have been developed, few of them have been validated and used in clinical practice, but with unsatisfactory performances. Thus, there is still a need to rigorously validate many of these novel promising biomarkers in large-scale longitudinal studies and also identify better biomarkers not only for lupus diagnosis but also for monitoring and predicting upcoming flares and response to treatment. Besides serological biomarkers, urinary and cerebrospinal fluid biomarkers have emerged for assessing both renal and central nervous system involvement in systemic lupus erythematosus, respectively. Also, novel omics techniques help us to understand the molecular basis of the disease and also allow the identification of novel biomarkers which may be potentially useful for guiding new therapeutic targets.
IlleiGGTackeyELaptevaLLipskyPE.Biomarkers in systemic lupus erythematosus. I. General overview of biomarkers and their applicability. Arthritis Rheum2004;
50: 1709–1720.
2.
SchiffenbauerJHahnBWeismanMHSimonLS.Biomarkers, surrogate markers, and design of clinical trials of new therapies for systemic lupus erythematosus. Arthritis Rheum2004;
50: 2415–2422.
3.
Biomarkers Definitions Working Group.
Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther2001;
69: 89–95.
4.
AhearnJMLiuCManziS.Lupus biomarker discovery, validation, approval, and impact on clinical trials. Curr Treat Options in Rheum2015;
1: 1–9.
5.
AhearnJMLiuCCKaoAHManziS.Biomarkers for systemic lupus erythematosus. Transl Res2012;
159: 326–342.
6.
MokCC.Biomarkers for lupus nephritis: a critical appraisal. J Biomed Biotechnol2010;
2010: 638413.
7.
LiuCCAhearnJM.The search for lupus biomarkers. Best Pract Res Clin Rheumatol2009;
23: 507–523.
8.
WuHZengJYinJPengQZhaoMLuQ.Organ-specific biomarkers in lupus. Autoimmun Rev2017;
16: 391–397.
9.
LiuCCKaoAHManziSAhearnJM.Biomarkers in systemic lupus erythematosus: challenges and prospects for the future. Ther Adv Musculoskelet Dis2013;
5: 210–233.
10.
FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools) Resource [Internet]. Silver Spring (MD): Food and Drug Administration (US), 2016. https://www.ncbi.nlm.nih.gov/books/NBK326791/Co-published. Bethesda: National Institutes of Health (US).
11.
MiglioriniPBaldiniCRocchiVBombardieriS.Anti-Sm and anti-RNP antibodies. Autoimmunity2005;
38: 47–54.
12.
MoroniGTrendelenburgMDel PapaN, et al.
Anti-C1q antibodies may help in diagnosing a renal flare in lupus nephritis. Am J Kidney Dis2001;
37: 490–498.
13.
SinicoRARadiceAIkehataM, et al.
Anti-C1q autoantibodies in lupus nephritis: prevalence and clinical significance. Ann N Y Acad Sci2005;
1050: 193–200.
14.
StohlWHilbertDM.The discovery and development of belimumab: the anti-BLyS-lupus connection. Nat Biotechnol2012;
30: 69–77.
15.
RellingMVGardnerEESandbornWJ, et al.; Clinical Pharmacogenetics Implementation Consortium.
Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clin Pharmacol Ther2011;
89: 387–391.
16.
AvihingsanonYPhumesinPBenjachatT, et al.
Measurement of urinary chemokine and growth factor messenger RNAs: a noninvasive monitoring in lupus nephritis. Kidney Int2006;
69: 747–753.
17.
SmithTJBohlkeKLymanGH, et al.; American Society of Clinical Oncology.
Recommendations for the use of WBC growth factors: American society of clinical oncology clinical practice guideline update. J Clin Oncol2015;
33: 3199–3212.
18.
NiuZZhangPTongY.Value of HLA-DR genotype in systemic lupus erythematosus and lupus nephritis: a meta-analysis. Int J Rheum Dis2015;
18: 17–28.
19.
TruedssonLBengtssonAASturfeltG.Complement deficiencies and systemic lupus erythematosus. Autoimmunity2007;
40: 560–566.
20.
HochbergMC.Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum1997;
40: 1725.
21.
PetriMOrbaiAMAlarcónGS, et al.
Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum2012;
64: 2677–2686.
22.
AringerMCostenbaderKDaikhD, et al.
2019 European league against rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis2019;
78: 1151–1159.
23.
ArbuckleMRMcClainMTRubertoneMV, et al.
Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med2003;
349: 1526–1533.
24.
KavanaughATomarRReveilleJSolomonDHHomburgerHA.Guidelines for clinical use of the antinuclear antibody test and tests for specific autoantibodies to nuclear antigens. American college of pathologists. Arch Pathol Lab Med2000;
124: 71–81.
25.
Amezcua-GuerraLMHiguera-OrtizVArteaga-GarcíaUGallegos-NavaSHübbe-TenaC.Performance of the 2012 systemic lupus international collaborating clinics and the 1997 American College of Rheumatology classification criteria for systemic lupus erythematosus in a Real-Life scenario. Arthritis Care Res (Hoboken)2015;
67: 437–441.
26.
LarosaMIaccarinoLGattoMPunziLDoriaA.Advances in the diagnosis and classification of systemic lupus erythematosus. Expert Rev Clin Immunol2016;
12: 1309–1320.
27.
ReveilleJD.Predictive value of autoantibodies for activity of systemic lupus erythematosus. Lupus2004;
13: 290–297.
28.
HeinlenLDMcClainMTMerrillJ, et al.
Clinical criteria for systemic lupus erythematosus precede diagnosis, and associated autoantibodies are present before clinical symptoms. Arthritis Rheum2007;
56: 2344–2351.
29.
KavanaughAFSolomonDH; American College of Rheumatology Ad Hoc Committee on Immunologic Testing Guidelines.
Guidelines for immunologic laboratory testing in the rheumatic diseases: anti-DNA antibody tests. Arthritis Rheum2002;
47: 546–555.
30.
HaugbroKNossentJCWinklerTFigenschauYRekvigOP.Anti-dsDNA antibodies and disease classification in antinuclear antibody positive patients: the role of analytical diversity. Ann Rheum Dis2004;
63: 386–394.
31.
OlsenNJKarpDR.Autoantibodies and SLE: the threshold for disease. Nat Rev Rheumatol2014;
10: 181–186.
32.
ChoiMYFitzPatrickRDBuhlerKMahlerMFritzlerMJ.A review and meta-analysis of anti-ribosomal P autoantibodies in systemic lupus erythematosus. Autoimmun Rev2020;
19: 102463.
33.
PasotoSGVianaVSBonfaE.The clinical utility of anti-ribosomal P autoantibodies in systemic lupus erythematosus. Expert Rev Clin Immunol2014;
10: 1493–1503.
34.
MahlerMKessenbrockKSzmyrkaM, et al.
International multicenter evaluation of autoantibodies to ribosomal P proteins. Cvi2006;
13: 77–83.
35.
HaddoukSMarzoukSJallouliM, et al.
Clinical and diagnostic value of ribosomal P autoantibodies in systemic lupus erythematosus. Rheumatology (Oxford)2009;
48: 953–957.
36.
HanlyJGUrowitzMBSiannisF, et al.; Systemic Lupus International Collaborating Clinics.
Autoantibodies and neuropsychiatric events at the time of systemic lupus erythematosus diagnosis: results from an international inception cohort study. Arthritis Rheum2008;
58: 843–853.
37.
ReichlinMBroylesTFHubscherO, et al.
Prevalence of autoantibodies to ribosomal P proteins in juvenile-onset systemic lupus erythematosus compared with the adult disease. Arthritis Rheum1999;
42: 69–75.
38.
PisoniCNMuñozSACarrizoC, et al.
Multicentric prevalence study of anti P ribosomal autoantibodies in juvenile onset systemic lupus erythematosus compared with adult onset systemic lupus erythematosus. Reumatol Clin2015;
11: 73–77.
39.
LiHLinSYangSChenLZhengX.Diagnostic value of serum complement C3 and C4 levels in Chinese patients with systemic lupus erythematosus. Clin Rheumatol2015;
34: 471–477.
AhearnJMLiuCCManziS.Cell-bound complement activation products as lupus biomarkers: diagnosis, monitoring and stratification. Expert Rev Clin Immunol2017;
13: 1133–1142.
42.
ManziSNavratilJSRuffingMJ, et al.
Measurement of erythrocyte C4d and complement receptor 1 in systemic lupus erythematosus. Arthritis Rheum2004;
50: 3596–3604.
43.
NavratilJSManziSKaoAH, et al.
Platelet C4d is highly specific for systemic lupus erythematosus. Arthritis Rheum2006;
54: 670–674.
44.
LiuCCKaoAHHawkinsDM, et al.
Lymphocyte-bound complement activation products as biomarkers for diagnosis of systemic lupus erythematosus. Clin Transl Sci2009;
2: 300–308.
45.
LoodCErikssonSGullstrandB, et al.
Increased C1q, C4 and C3 deposition on platelets in patients with systemic lupus erythematosus–a possible link to venous thrombosis?Lupus2012;
21: 1423–1432.
46.
KalunianKCChathamWWMassarottiEM, et al.
Measurement of cell-bound complement activation products enhances diagnostic performance in systemic lupus erythematosus. Arthritis Rheum2012;
64: 4040–4047.
47.
PuttermanCFurieRRamsey-GoldmanR, et al.
Cell-bound complement activation products in systemic lupus erythematosus: comparison with anti-double-stranded DNA and standard complement measurements. Lupus Sci Med2014;
1: e000056.
48.
WallaceDJSilvermanSLConklinJBarkenDDervieuxT.Systemic lupus erythematosus and primary fibromyalgia can be distinguished by testing for cell-bound complement activation products. Lupus Sci Med2016;
3: e000127.
49.
MossellJGoldmanJABarkenDAlexanderRV.The avise lupus test and cell-bound complement activation products aid the diagnosis of systemic lupus erythematosus. Open Rheumatol J2016;
10: 71–80.
50.
WallaceDJAlexanderRVO'MalleyT, et al.
Randomised prospective trial to assess the clinical utility of multianalyte assay panel with complement activation products for the diagnosis of SLE. Lupus Sci Med2019;
6: e000349.
51.
Ramsey-GoldmanRAlexanderRVMassarottiEM, et al.
Complement activation in patients with probable systemic lupus erythematosus and ability to predict progression to American College of Rheumatology-classified systemic lupus erythematosus. Arthritis Rheumatol2020;
72: 78–88.
52.
Hui-YuenJSGartshteynYMaM, et al.
Cell-bound complement activation products (CB-CAPs) have high sensitivity and specificity in pediatric-onset systemic lupus erythematosus and correlate with disease activity. Lupus2018;
27: 2262–2268.
53.
BuyonJPTameriusJBelmontHMAbramsonSB.Assessment of disease activity and impending flare in patients with systemic lupus erythematosus. Comparison of the use of complement split products and conventional measurements of complement. Arthritis Rheum1992;
35: 1028–1037.
DervieuxTConklinJLigayonJA, et al.
Validation of a multi-analyte panel with cell-bound complement activation products for systemic lupus erythematosus. J Immunol Methods2017;
446: 54–59.
56.
BizzaroNVillaltaDGiavarinaDTozzoliR.Are anti-nucleosome antibodies a better diagnostic marker than anti-dsDNA antibodies for systemic lupus erythematosus? a systematic review and a study of metanalysis. Autoimmun Rev2012;
12: 97–106.
57.
MehraSFritzlerMJ.The spectrum of anti-chromatin/nucleosome autoantibodies: independent and interdependent biomarkers of disease. J Immunol Res2014;
2014: 368274.
58.
MinDJKimSJParkSH, et al.
Anti-nucleosome antibody: significance in lupus patients lacking anti-double-stranded DNA antibody. Clin Exp Rheumatol2002;
20: 13–18.
59.
RekvigOPvan der VlagJSeredkinaN.Review: antinucleosome antibodies: a critical reflection on their specificities and diagnostic impact. Arthritis Rheumatol2014;
66: 1061–1069.
60.
BombardierCGladmanDDUrowitzMBCaronDChangCH.Derivation of the SLEDAI. A disease activity index for lupus patients. The committee on prognosis studies in SLE. Arthritis Rheum1992;
35: 630–640.
61.
LiangMHSocherSALarsonMGSchurPH.Reliability and validity of six systems for the clinical assessment of disease activity in systemic lupus erythematosus. Arthritis Rheum1989;
32: 1107–1118.
62.
HayEMBaconPAGordonC, et al.
The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus. Q J Med1993;
86: 447–458.
DavisPPercyJSRussellAS.Correlation between levels of DNA antibodies and clinical disease activity in SLE. Ann Rheum Dis1977;
36: 157–159.
65.
MerrillJTPetriMABuyonJ, et al.
Erythrocyte-bound C4d in combination with complement and autoantibody status for the monitoring of SLE. Lupus Sci Med2018;
5: e000263.
66.
AlarcónGSCalvo-AlenJMcGwinGJr, et al.; for the LUMINA Study Group.
Systemic lupus erythematosus in a multiethnic cohort: LUMINA XXXV. Predictive factors of high disease activity over time. Ann Rheum Dis2006;
65: 1168–1174.
BastianHMRosemanJMMcGwinGJr, et al.; Lumina Study Group.
Systemic lupus erythematosus in three ethnic groups. XII. Risk factors for lupus nephritis after diagnosis. Lupus2002;
11: 152–160.
69.
MitjavilaFPacVMogaI, et al.
Clinicopathological correlations and prognostic factors in lupus nephritis. Clin Exp Rheumatol1997;
15: 625– 631.
70.
SchurPHSandsonJ.Immunologic factors and clinical activity in systemic lupus erythematosus. N Engl J Med1968;
278: 533–538.
71.
IsenbergDAGartonMReichlinMWReichlinM.Long-term Follow-Up of autoantibody profiles in black female lupus patients and clinical comparison with Caucasian and Asian patients. Br J Rheumatol1997;
36: 229–233.
72.
Cortés-HernándezJOrdi-RosJLabradorM, et al.
Antihistone and anti-double-stranded deoxyribonucleic acid antibodies are associated with renal disease in systemic lupus erythematosus. Am J Med2004;
116: 165–173.
73.
BastianHMAlarcónGSRosemanJM, et al.; for the LUMINA Study Group.
Systemic lupus erythematosus in a multiethnic US cohort (LUMINA) XL II: factors predictive of new or worsening proteinuria. Rheumatology (Oxford2006;
46: 683–689.
74.
RavirajanCTRowseLMacGowanJRIsenbergDA.An analysis of clinical disease activity and nephritis-associated serum autoantibody profiles in patients with systemic lupus erythematosus: a cross-sectional study. Rheumatology (Oxford)2001;
40: 1405–1412.
75.
PetriMAvan VollenhovenRFBuyonJ, BLISS-52 and BLISS-76 Study Groupset al.
Baseline predictors of systemic lupus erythematosus flares: data from the combined placebo groups in the phase III belimumab trials. Arthritis Rheum2013;
65: 2143–2153.
76.
ter BorgEJHorstGHummelEJLimburgPCKallenbergCG.Measurement of increases in anti-double-stranded DNA antibody levels as a predictor of disease exacerbation in systemic lupus erythematosus. A long-term, prospective study. Arthritis Rheum1990;
33: 634–643.
77.
SwaakAJGroenwoldJBronsveldW.Predictive value of complement profiles and anti-dsDNA in systemic lupus erythematosus. Ann Rheum Dis1986;
45: 359–366.
78.
StohlWHiepeFLatinisKM, et al.; BLISS-76 Study Group.
Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus. Arthritis Rheum2012;
64: 2328–2337.
79.
TsengCEBuyonJPKimM, et al.
The effect of moderate-dose corticosteroids in preventing severe flares in patients with serologically active, but clinically stable, systemic lupus erythematosus: findings of a prospective, randomized, double-blind, placebo-controlled trial. Arthritis Rheum2006;
54: 3623–3632.
80.
RovinBHFurieRLatinisK, et al.; LUNAR Investigator Group.
Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the lupus nephritis assessment with rituximab study. Arthritis Rheum2012;
64: 1215–1226.
81.
PisetskyDS.Anti-DNA antibodies–quintessential biomarkers of SLE. Nat Rev Rheumatol2016;
12: 102–110.
82.
SteimanAJUrowitzMBIbañezDLiTTGladmanDDWitherJ.Anti-dsDNA and antichromatin antibody isotypes in serologically active clinically quiescent systemic lupus erythematosus. J Rheumatol2015;
42: 810–816.
83.
de LeeuwKBungenerLRoozendaalCBootsmaHStegemanCA.Auto-antibodies to double-stranded DNA as biomarker in systemic lupus erythematosus: comparison of different assays during quiescent and active disease. Rheumatology (Oxford)2017;
56: 698–703.
84.
LefflerJBengtssonAABlomAM.The complement system in systemic lupus erythematosus: an update. Ann Rheum Dis2014;
73: 1601–1606.
85.
HoABarrSGMagderLSPetriM.A decrease in complement is associated with increased renal and hematologic activity in patients with systemic lupus erythematosus. Arthritis Rheum2001;
44: 2350–2357.
86.
SchejbelLSkattumLHagelbergS, et al.
Molecular basis of hereditary C1q deficiency–revisited: identification of several novel disease-causing mutations. Genes Immun2011;
12: 626–634.
87.
OrbaiAMTruedssonLSturfeltG, et al.
Anti-C1q antibodies in systemic lupus erythematosus. Lupus2015;
24: 42–49.
88.
StojanGPetriM.Anti-C1q in systemic lupus erythematosus. Lupus2016;
25: 873–877.
SinicoRARimoldiLRadiceABianchiLGallelliBMoroniG.Anti-C1q autoantibodies in lupus nephritis. Ann N Y Acad Sci2009;
1173: 47–51.
91.
MartoNBertolacciniMLCalabuigEHughesGRKhamashtaMA.Anti-C1q antibodies in nephritis: correlation between titres and renal disease activity and positive predictive value in systemic lupus erythematosus. Ann Rheum Dis2004;
64: 444–448.
92.
TrendelenburgMMarfurtJGerberITyndallASchifferliJA.Lack of occurrence of severe lupus nephritis among anti-C1q autoantibody-negative patients. Arthritis Rheum1999;
42: 187–188.
93.
TrendelenburgMLopez-TrascasaM,PotlukovaE, et al.
High prevalence of anti-C1q antibodies in biopsy proven active lupus nephritis. Nephrol Dial Transplant2006;
21: 3115–3121.
94.
MoroniGRadiceAGiammarresiG, et al.
Are laboratory tests useful for monitoring the activity of lupus nephritis? A six-year prospective study in a cohort of 228 lupus nephritis patients. Ann Rheum Dis2009;
68: 234–237.
95.
MatratAVeysseyre-BalterCTrollietP, et al.
Simultaneous detection of anti-C1q and anti-double stranded DNA autoantibodies in lupus nephritis: predictive value for renal flares. Lupus2011;
20: 28–34.
96.
DimaAOprisDJurcutCBaicusC.Is there still a place for erythrocyte sedimentation rate and C-reactive protein in systemic lupus erythematosus?Lupus2016;
25: 1173–1179.
97.
ViláLMAlarcónGSMcGwinGJrBastianHMFesslerBJReveilleJD.Systemic lupus erythematosus in a multiethnic cohort (LUMINA): XXIX. Elevation of erythrocyte sedimentation rate is associated with disease activity and damage accrual. J Rheumatol2005;
32: 2150–2155.
98.
StojanGFangHMagderLPetriM.Erythrocyte sedimentation rate is a predictor of renal and overall SLE disease activity. Lupus2013;
22: 827–834.
99.
BertoliAMViláLMReveilleJDAlarcónGS.Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): LXI. Value of C-reactive protein as a marker of disease activity and damage. J Rheumatol2008;
35: 2355–2358.
100.
EudyAMVinesAIDooleyMACooperGSParksCG.Elevated C-reactive protein and self-reported disease activity in systemic lupus erythematosus. Lupus2014;
23: 1460–1467.
101.
Jackish JG, Somers E and McCune J. Comparison of ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein) in lupus patients presenting with fever [Abstract]. In: American College of Rheumatology, Annual Scientific Meeting, Washington, DC, USA, 2006, L22. University of Michigan-Ann Arbor, Ann Arbor.
102.
LiuCCManziSKaoAHNavratilJSRuffingMJAhearnJM.Reticulocytes bearing C4d as biomarkers of disease activity for systemic lupus erythematosus. Arthritis Rheum2005;
52: 3087–3099.
103.
KaoAHNavratilJSRuffingMJ, et al.
Erythrocyte C3d and C4d for monitoring disease activity in systemic lupus erythematosus. Arthritis Rheum2010;
62: 837–844.
104.
YangDHChangDMLaiJHLinFHChenCH.Usefulness of erythrocyte-bound C4d as a biomarker to predict disease activity in patients with systemic lupus erythematosus. Rheumatology (Oxford)2009;
48: 1083–1087.
105.
BuyonJFurieRPuttermanC, et al.
Reduction in erythrocyte-bound complement activation products and titres of anti-C1q antibodies associate with clinical improvement in systemic lupus erythematosus. Lupus Sci Med2016;
3: e000165.
106.
HooksJJMoutsopoulosHMGeisSAStahlNIDeckerJLNotkinsAL.Immune interferon in the circulation of patients with autoimmune disease. N Engl J Med1979;
301: 5–8.
107.
BaechlerECBatliwallaFMKarypisG, et al.Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A2003;
100: 2610–2615.
108.
KirouKALeeCGeorgeSLoucaKPetersonMGECrowMK.Of the interferon-α pathway identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease. Arthritis Rheum2005;
52: 1491–1503.
109.
FengXWuHGrossmanJM, et al.
Association of increased interferon-inducible gene expression with disease activity and lupus nephritis in patients with systemic lupus erythematosus. Arthritis Rheum2006;
54: 2951–2962.
110.
BauerJWBaechlerECPetriM, et al.
Elevated serum levels of interferon-regulated chemokines are biomarkers for active human systemic lupus erythematosus. PLoS Med2006;
3: e491.
111.
BauerJWPetriMBatliwallaFM, et al.
Interferon-regulated chemokines as biomarkers of systemic lupus erythematosus disease activity: a validation study. Arthritis Rheum2009;
60: 3098–3107.
112.
NikpourMDempseyAAUrowitzMBGladmanDD andBarnesDA.Association of a gene expression profile from whole blood with disease activity in systemic lupus erythaematosus. Ann Rheum Dis2008;
67: 1069–1075.
113.
RoseTGrützkauAHirselandH, et al.
IFNα and its response proteins, IP-10 and SIGLEC-1, are biomarkers of disease activity in systemic lupus erythematosus. Ann Rheum Dis2013;
72: 1639–1645.
114.
Landolt-MarticorenaCBonventiGLubovichA, et al.
Lack of association between the interferon-alpha signature and longitudinal changes in disease activity in systemic lupus erythematosus. Ann Rheum Dis2009;
68: 1440–1446.
115.
PetriMSinghSTesfasyoneH, et al.
Longitudinal expression of type I interferon responsive genes in systemic lupus erythematosus. Lupus2009;
18: 980–989.
116.
PetriMFuWRangerA, et al.
Association between changes in gene signatures expression and disease activity among patients with systemic lupus erythematosus. BMC Med Genomics2019;
12: 4.
117.
ChicheLJourde-ChicheNWhalenE, et al.
Modular transcriptional repertoire analyses of adults with systemic lupus erythematosus reveal distinct type I and type II interferon signatures. Arthritis Rheumatol2014;
66: 1583–1595.
118.
RoseTGrützkauAKlotscheJ, et al.
Are interferon-related biomarkers advantageous for monitoring disease activity in systemic lupus erythematosus? A longitudinal benchmark study. Rheumatology (Oxford)2017;
56: 1618–1626.
119.
MackayFSchneiderP.Cracking the BAFF code. Nat Rev Immunol2009;
9: 491–502.
120.
VincentFBNorthcottMHoiAMackayFMorandEF.Association of serum B cell activating factor from the tumour necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) with Central nervous system and renal disease in systemic lupus erythematosus. Lupus2013;
22: 873–884.
121.
PetriMStohlWChathamW, et al.
Association of plasma B lymphocyte stimulator levels and disease activity in systemic lupus erythematosus. Arthritis Rheum2008;
58: 2453–2459.
122.
HegazyMDarwishHDarweeshHEl-ShehabyAEmadY.Raised serum level of APRIL in patients with systemic lupus erythematosus: correlations with disease activity indices. Clin Immunol2010;
135: 118–124.
123.
StohlWMetyasSTanSM, et al.
Inverse association between circulating APRIL levels and serological and clinical disease activity in patients with systemic lupus erythematosus. Ann Rheum Dis2004;
63: 1096–1103.
124.
Becker-MerokANikolaisenCNossentHC.B-lymphocyte activating factor in systemic lupus erythematosus and rheumatoid arthritis in relation to autoantibody levels, disease measures and time. Lupus2006;
15: 570–576.
125.
ZhaoLDLiYSmithMF, et al.
Expressions of BAFF/BAFF receptors and their correlation with disease activity in Chinese SLE patients. Lupus2010;
19: 1534–1549.
126.
Salazar-CamarenaDCOrtiz-LazarenoPCCruzA, et al.
Association of BAFF, APRIL serum levels, BAFF-R, TACI and BCMA expression on peripheral B-cell subsets with clinical manifestations in systemic lupus erythematosus. Lupus2016;
25: 582–592.
127.
CarterLMIsenbergDAEhrensteinMR.Elevated serum BAFF levels are associated with rising anti-double-stranded DNA antibody levels and disease flare following B cell depletion therapy in systemic lupus erythematosus. Arthritis Rheum2013;
65: 2672–2679.
128.
RitterhouseLLCroweSRNiewoldTB, et al.
B lymphocyte stimulator levels in systemic lupus erythematosus: higher circulating levels in African American patients and increased production after influenza vaccination in patients with low baseline levels. Arthritis Rheum2011;
63: 3931–3941.
129.
MorelJRoubilleCPlanellesL, et al.
Serum levels of tumour necrosis factor family members a proliferation-inducing ligand (APRIL) and B lymphocyte stimulator (BLyS) are inversely correlated in systemic lupus erythematosus. Ann Rheum Dis2009;
68: 997–1002.
130.
CollinsCEGavinALMigoneTSHilbertDMNemazeeDStohlW.B lymphocyte stimulator (BLyS) isoforms in systemic lupus erythematosus: disease activity correlates better with blood leukocyte BLyS mRNA levels than with plasma BLyS protein levels. Arthritis Res Ther2006;
8: R6.
131.
StohlWMetyasSTanSM, et al.
B lymphocyte stimulator overexpression in patients with systemic lupus erythematosus: longitudinal observations. Arthritis Rheum2003;
48: 3475–3486.
132.
VincentFBMorandEFSchneiderPMackayF.The BAFF/APRIL system in SLE pathogenesis. Nat Rev Rheumatol2014;
10: 365–373.
133.
CasterDJMerchantMLKleinJBPowellDW.Precision medicine in lupus nephritis: can biomarkers get us there?Transl Res2018;
201: 26–39.
134.
AragónCCTafúrRASuárez-AvellanedaAMartínezMTSalasALTobónGJ.Urinary biomarkers in lupus nephritis. J Transl Autoimmun2020;
3: 100042.
IwanoMDohiKHirataE, et al.
Urinary levels of IL-6 in patients with active lupus nephritis. Clin Nephrol1993;
40: 16–21.
137.
SusiantiHIrianeVMDharmanataS, et al.
Analysis of urinary TGF-β1, MCP-1, NGAL, and IL-17 as biomarkers for lupus nephritis. Pathophysiology2015;
22: 65–71.
138.
Abdel GalilSMEzzeldinNEl-BoshyME.The role of serum IL-17 and IL-6 as biomarkers of disease activity and predictors of remission in patients with lupus nephritis. Cytokine2015;
76: 280–287.
139.
SchwartzNSuLBurklyLC, et al.
Urinary TWEAK and the activity of lupus nephritis. J Autoimmun2006;
27: 242–250.
140.
SchwartzNRubinsteinTBurklyLC, et al.
Urinary TWEAK as a biomarker of lupus nephritis: a multicenter cohort study. Arthritis Res Ther2009;
11: R143.
141.
MiriogluSCinarSYaziciH, et al.
Serum and urine TNF-like weak inducer of apoptosis, monocyte chemoattractant protein-1 and neutrophil gelatinase-associated lipocalin as biomarkers of disease activity in patients with systemic lupus erythematosus. Lupus2020;
29: 379–388.
142.
RovinBHSongH.Chemokine induction by the adipocyte-derived cytokine. Clin Immunol2006;
120: 99–105.
143.
RovinBHSongHHebertLA, et al.
Plasma, urine, and renal expression of adiponectin in human systemic lupus erythematosus. Kidney Int2005;
68: 1825–1833.
144.
Gómez-PuertaJAOrtiz-ReyesBUrregoT, et al.
Urinary neutrophil gelatinase-associated lipocalin and monocyte chemoattractant protein 1 as biomarkers for lupus nephritis in Colombian SLE patients. Lupus2018;
27: 637–646.
145.
KianiANJohnsonKChenC, et al.
Urine osteoprotegerin and monocyte chemoattractant protein-1 in lupus nephritis. J Rheumatol2009;
36: 2224–2230.
146.
RovinBHSongHBirminghamDJHebertLAYuCYNagarajaHN.Urine chemokines as biomarkers of human systemic lupus erythematosus activity. J Am Soc Nephrol2005;
16: 467–473.
147.
GuptaRYadavAAggarwalA.Longitudinal assessment of monocyte chemoattractant protein-1 in lupus nephritis as a biomarker of disease activity. Clin Rheumatol2016;
35: 2707–2714.
148.
AbujamBCheekatlaSAggarwalA.Urinary CXCL-10/IP-10 and MCP-1 as markers to assess activity of lupus nephritis. Lupus2013;
22: 614–623.
149.
XiaYRLiQRWangJP, et al.
Diagnostic value of urinary monocyte chemoattractant protein-1 in evaluating the activity of lupus nephritis: a meta-analysis. Lupus2020;
29: 599–606.
150.
MarieMAAbu KhalilREHabibHM.Urinary CXCL10: a marker of nephritis in lupus patients. Reumatismo2014;
65: 292–297.
151.
WuTXieCWangHW, et al.
Elevated urinary VCAM-1, P-Selectin, soluble TNF receptor-1, and CXC chemokine ligand 16 in multiple murine lupus strains and human lupus nephritis. J Immunol2007;
179: 7166–7175.
152.
TianSLiJWangL, et al.
Urinary levels of RANTES and M-CSF are predictors of lupus nephritis flare. Inflamm Res2007;
56: 304–310.
153.
HassanAMFarghalNMAHegabDSMohamedWSAbd-ElnabiHH.Serum-soluble CXCL16 in juvenile systemic lupus erythematosus: a promising predictor of disease severity and lupus nephritis. Clin Rheumatol2018;
37: 3025–3032.
154.
GasparinAAPamplona Bueno de AndradeNHaxVTresGLVeroneseFVMonticieloOA.Urinary biomarkers for lupus nephritis: the role of the vascular cell adhesion molecule-1. Lupus2019;
28: 265–272.
155.
HoweHSKongKOThongBY, et al.
Urine sVCAM-1 and sICAM-1 levels are elevated in lupus nephritis. Int J Rheum Dis2012;
15: 13–16.
156.
WuCYangMZhouZ, et al.
Urinary soluble intercellular adhesion molecule-1 and vascular cellular adhesion molecule-1: potential biomarkers of active lupus nephritis. Nan Fang Yi Ke Da Xue Xue Bao2015;
35: 1272–1276.
157.
Abd-ElkareemMIAl TamimyHMKhamisOAAbdellatifSSHusseinMRA.Increased urinary levels of the leukocyte adhesion molecules ICAM-1 and VCAM-1 in human lupus nephritis with advanced renal histological changes: preliminary findings. Clin Exp Nephrol2010;
14: 548–557.
158.
SinghSWuTXieC, et al.
Urine VCAM-1 as a marker of renal pathology activity index in lupus nephritis. Arthritis Res Ther2012;
14: R164.
159.
Guo LiuRNChengQYZhouHYLiBZYeDQ.Elevated blood and urinary ICAM-1 is a biomarker for systemic lupus erythematosus: a systematic review and meta-analysis. Immunol Invest2020;
49: 15–31.
160.
SingerEMarkóLParagasN, et al.
Neutrophil gelatinase-associated lipocalin: pathophysiology and clinical applications. Acta Physiol (Oxf)2013;
207: 663–672.
161.
RubinsteinTPitashnyMPuttermanC.The novel role of neutrophil gelatinase-B associated lipocalin (NGAL)/lipocalin-2 as a biomarker for lupus nephritis. Autoimmun Rev2008;
7: 229–234.
162.
BrunnerHIMuellerMRutherfordC, et al.
Urinary neutrophil gelatinase-associated lipocalin as a biomarker of nephritis in childhood-onset systemic lupus erythematosus. Arthritis Rheum2006;
54: 2577–2584.
163.
YangCCHsiehSCLiKJ, et al.
Urinary neutrophil gelatinase-associated lipocalin is a potential biomarker for renal damage in patients with systemic lupus erythematosus. J Biomed Biotechnol2012;
2012: 759313.
164.
GaoYWangBCaoJFengSLiuB.Elevated urinary neutrophil gelatinase-associated lipocalin is a biomarker for lupus nephritis: a systematic review and meta-analysis. Biomed Res Int2020;
2020: 2768326.
165.
BurbanoCGómez-PuertaJAMuñoz-VahosC, et al.
HMGB1+ microparticles present in urine are hallmarks of nephritis in patients with systemic lupus erythematosus. Eur J Immunol2019;
49: 323–335.
166.
PhatakSChaurasiaSMishraSK, et al.
Urinary B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL): potential biomarkers of active lupus nephritis. Clin Exp Immunol2017;
187: 376–382.
167.
HanlyJGKozoraEBeyeaSDBirnbaumJ.Review: nervous system disease in systemic lupus erythematosus: current status and future directions. Arthritis Rheumatol2019;
71: 33–42.
168.
Magro-ChecaCSteup-BeekmanGMHuizingaTWvan BuchemMARonenI.Laboratory and neuroimaging biomarkers in neuropsychiatric systemic lupus erythematosus: where do we stand, where to go?Front Med (Lausanne)2018;
5: 340.
Zandman-GoddardGChapmanJShoenfeldY.Autoantibodies involved in neuropsychiatric SLE and antiphospholipid syndrome. Semin Arthritis Rheum2007;
36: 297–315.
171.
HoRCThiaghuCOngH, et al.
A Meta-analysis of serum and cerebrospinal fluid autoantibodies in neuropsychiatric systemic lupus erythematosus. Autoimmun Rev2016;
15: 124–138.
172.
KarassaFBAfeltraAAmbrozicA, et al.
Accuracy of anti-ribosomal P protein antibody testing for the diagnosis of neuropsychiatric systemic lupus erythematosus: an international meta-analysis. Arthritis Rheum2006;
54: 312–324.
173.
ArinumaYYanagidaTHirohataS.Association of cerebrospinal fluid anti-NR2 glutamate receptor antibodies with diffuse neuropsychiatric systemic lupus erythematosus. Arthritis Rheum2008;
58: 1130–1135.
174.
Fragoso-LoyoHCabiedesJOrozco-NarváezA, et al.
Serum and cerebrospinal fluid autoantibodies in patients with neuropsychiatric lupus erythematosus. Implications for diagnosis and pathogenesis. PLoS One2008;
3: e3347.
175.
TaySHFairhurstAMMakA.Clinical utility of circulating anti-N-methyl-d-aspartate receptor subunits NR2A/B antibody for the diagnosis of neuropsychiatric syndromes in systemic lupus erythematosus and sjögren's syndrome: an updated meta-analysis. Autoimmun Rev2017;
16: 114–122.
176.
Fragoso-LoyoHRichaud-PatinYOrozco-NarváezA, et al.
Interleukin-6 and chemokines in the neuropsychiatric manifestations of systemic lupus erythematosus. Arthritis Rheum2007;
56: 1242–1250.
177.
George-ChandyATrysbergEErikssonK.Raised intrathecal levels of APRIL and BAFF in patients with systemic lupus erythematosus: relationship to neuropsychiatric symptoms. Arthritis Res Ther2008;
10: R97.
178.
BertsiasGKIoannidisJPAringerM, et al.
EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs. Ann Rheum Dis2010;
69: 2074–2082.
179.
SarbuNToledanoPCalvoA, et al.
Advanced MRI techniques: biomarkers in neuropsychiatric lupus. Lupus2017;
26: 510–516.
180.
SongWTangDChenD, et al.
Advances in applying of multi-omics approaches in the research of systemic lupus erythematosus. Int Rev Immunol2020;
39: 163–173.
181.
TeruelMChamberlainCAlarcón-RiquelmeME.Omics studies: their use in diagnosis and reclassification of SLE and other systemic autoimmune diseases. Rheumatology (Oxford)2017;
56: i78–i87.
182.
OparinaNMartínez-BuenoMAlarcón-RiquelmeME.An update on the genetics of systemic lupus erythematosus. Curr Opin Rheumatol2019;
31: 659–668.
183.
BreitbachMERamakerRCRobertsKKimberlyRPAbsherD.Population-specific patterns of epigenetic defects in the B cell lineage in patients with systemic lupus erythematosus. Arthritis Rheumatol2020;
72: 282–291.
184.
RichardsonB.Epigenetically altered T cells contribute to lupus flares. Cells2019;
8: 127.
185.
WardowskaA.The epigenetic face of lupus: focus on antigen-presenting cells. Int Immunopharmacol2020;
81: 106262.
186.
CoitPJeffriesMAltorokN, et al.
Genome-wide DNA methylation study suggests epigenetic accessibility and transcriptional poising of interferon-regulated genes in naive CD4+ T cells from lupus patients. J Autoimmun2013;
43: 78–84.
187.
AbsherDMLiXWaiteLL, et al.
Genome-wide DNA methylation analysis of systemic lupus erythematosus reveals persistent hypomethylation of interferon genes and compositional changes to CD4+ T-cell populations. PLoS Genet2013;
9: e1003678.
188.
JeffriesMADozmorovMTangYMerrillJTWrenJDSawalhaAH.Genome-wide DNA methylation patterns in CD4+ T cells from patients with systemic lupus erythematosus. Epigenetics2011;
6: 593–601.
189.
ChungSANitithamJElboudwarejE, et al.
Genome-Wide assessment of differential DNA methylation associated with autoantibody production in systemic lupus erythematosus. PLoS One2015;
10: e0129813.
190.
CoitPDozmorovMGMerrillJT, et al.
Epigenetic reprogramming in naive CD4+ T cells favoring T cell activation and non-Th1 effector T cell immune response as an early event in lupus flares. Arthritis Rheumatol2016;
68: 2200–2209.
191.
ZhaoMZhouYZhuB, et al.
IFI44L promoter methylation as a blood biomarker for systemic lupus erythematosus. Ann Rheum Dis2016;
75: 1998–2006.
192.
ZanHTatCCasaliP.MicroRNAs in lupus. Autoimmunity2014;
47: 272–285.
193.
WuHChangCLuQ.The epigenetics of lupus erythematosus. Adv Exp Med Biol2020;
1253: 185–207.
194.
TesserAde CarvalhoLMSandrin-GarciaP, et al.
Higher interferon score and normal complement levels may identify a distinct clinical subset in children with systemic lupus erythematosus. Arthritis Res Ther2020;
22: 91.
195.
HasniSGuptaSDavisM, et al.
Safety and tolerability of omalizumab: a randomized clinical trial of humanized anti-IgE monoclonal antibody in systemic lupus erythematosus. Arthritis Rheumatol2019;
71: 1135–1140.
196.
KalunianKCMerrillJTMaciucaR, et al.
A phase II study of the efficacy and safety of rontalizumab (rhuMAb interferon-alpha) in patients with systemic lupus erythematosus (ROSE). Ann Rheum Dis2016;
75: 196–202.
197.
MistryPNakaboSO'NeilL, et al.
Transcriptomic, epigenetic, and functional analyses implicate neutrophil diversity in the pathogenesis of systemic lupus erythematosus. Proc Natl Acad Sci U S A2019;
116: 25222–25228.
198.
GrigoriouMBanosAFiliaA, et al.
Transcriptome reprogramming and myeloid skewing in haematopoietic stem and progenitor cells in systemic lupus erythematosus. Ann Rheum Dis2020;
79: 242–253.
199.
Udhaya KumarSThirumal KumarDSivaR, et al.
Dysregulation of signaling pathways due to differentially expressed genes from the B-Cell transcriptomes of systemic lupus erythematosus patients—a bioinformatics approach. Front Bioeng Biotechnol2020;
8: 276.
LiYWuT.Proteomic approaches for novel systemic lupus erythematosus (SLE) drug discovery. Expert Opin Drug Discov2018;
13: 765–777.
202.
NicolaouOKousiosAHadjisavvasALauwerysBSokratousKKyriacouK.Biomarkers of systemic lupus erythematosus identified using mass spectrometry-based proteomics: a systematic review. J Cell Mol Med2017;
21: 993–1012.
203.
AljaberiNBennettMBrunnerHIDevarajanP.Proteomic profiling of urine: implications for lupus nephritis. Expert Rev Proteom2019;
16: 303–313.
204.
ChenCGengLXuX, et al.
Comparative proteomics analysis of plasma protein in patients with neuropsychiatric systemic lupus erythematosus. Ann Transl Med2020;
8: 579.
205.
GuptaLAhmedSJainAMisraR.Emerging role of metabolomics in rheumatology. Int J Rheum Dis2018;
21: 1468–1477.
206.
JacobMLopataALDasoukiMAbdel RahmanAM.Metabolomics toward personalized medicine. Mass Spectrom Rev2019;
38: 221–238.
207.
GuleriaAPhatakSDubeyD, et al.
NMR-Based serum metabolomics reveals reprogramming of lipid dysregulation following cyclophosphamide-based induction therapy in lupus nephritis. J Proteome Res2018;
17: 2440–2448.
208.
OuyangXDaiYWenJLWangLX.1H NMR-based metabolomic study of metabolic profiling for systemic lupus erythematosus. Lupus2011;
20: 1411–1420.
209.
ZhangZWangYShenZ, et al.
The neurochemical and microstructural changes in the brain of systemic lupus erythematosus patients: a multimodal MRI study. Sci Rep2016;
6: 19026.
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