REVIEW

Threatening biomarkers in lupus pregnancy: Biochemistry and genetic challenges

  • Karim Mowla 1 ,
  • Elham Rajaei 1 ,
  • Mohammad Taha Jalali 2 ,
  • Zeinab Deris Zayeri , 1
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  • 1. Golestan Hospital Clinical Research Development Unit, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
  • 2. Hyperlipidemia Research Center, Diabetes Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Received date: 18 Oct 2017

Accepted date: 30 Nov 2017

Published date: 26 Mar 2018

Copyright

2017 Higher Education Press and Springer-Verlag GmbH Germany, part of Springer Nature

Abstract

OBJECTIVES: Using genetic markers and miRs work strongly beside other sensitive biomarkers in lupus management during sensitive period of pregnancy.

METHOD: PubMed and Google Scholar databases were searched from 2000 to 2017 using the terms “lupus,” “lupus pregnancy,” “biomarkers,” “micro-RNA,” “polymorphisms,” “anti-phospholipid antibodies,” and “cluster differentiation markers.”

DISCUSSION: Complement is a valuable biomarker in lupus pregnancy. However, the complement profile has ambiguous meaning because decreased levels of C3 and C4 reflect inflammation and because they are also prognostic biomarkers for abortion. Furthermore, increased C3 and C4 levels indicate hepatic protein synthesis in hepatocytes. Anti-phospholipid (APL) antibodies are present in 25% to 50% of lupus patients, and can lead to thrombotic and obstetric complications in some pregnancies and increase the risk of abortion, especially in a pregnant woman in the active phase of lupus. Several studies have associated APL with HELLP syndrome. However, other pregnancy complications have not been associated with APL. Autoantibodies against the major vault protein and anti-double strand DNA antibodies are valuable biomarkers in evaluating lupus activity. The expression pattern of micro-RNAs (miRs) differs in various diseases. Current studies have demonstrated the potential of miRs as diagnostic and prognostic biomarkers in various diseases; for example, the level of miR-126 is higher in lupus.

CONCLUSION: miR-223-3p and miR-451 are informative biomarkers in estimating disease activity. TWEAK, BAFF, and APOL1 genes, and their polymorphisms are informative in estimating disease activity, especially renal effects, and in monitoring higher-risk pregnant women. Further studies of these genes and their relevant polymorphisms are needed.

Cite this article

Karim Mowla , Elham Rajaei , Mohammad Taha Jalali , Zeinab Deris Zayeri . Threatening biomarkers in lupus pregnancy: Biochemistry and genetic challenges[J]. Frontiers in Biology, 2018 , 13(1) : 28 -35 . DOI: 10.1007/s11515-017-1477-8

Acknowledgements

We wish to thank all our colleagues in Golestan Hospital clinical research development unit, Ahvaz Jundishapur University of Medical Sciences.

Compliance with ethical standards

The authors declare no conflict of interest. This article does not contain any studies with human participants or animals performed by any of the authors.
1
Araki Y,Mimura T (2017). The histone modification code in the pathogenesis of autoimmune diseases. Mediators Inflamm, 2017:2608605

2
Badawi A I, El-Hamid A M A, Mohamed N K, Darwish E M M, Wassef M, Elfirgani H (2017). Serum tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and leptin as biomarkers of accelerated atherosclerosis in patients with systemic lupus erythematosus and antiphospholipid syndrome. Egyptian Rheumatologist, 39(2): 75–81

DOI

3
Balada E, Castro-Marrero J, Felip L, Ordi-Ros J, Vilardell-Tarrés M (2014). Clinical and serological findings associated with the expression of ITGAL, PRF1, and CD70 in systemic lupus erythematosus. Clin Exp Rheumatol, 32(1): 113–116

PMID

4
Ball E M, Gibson D S, Bell A L, Rooney M R (2014). Plasma IL-6 levels correlate with clinical and ultrasound measures of arthritis in patients with systemic lupus erythematosus. Lupus, 23(1): 46–56

DOI PMID

5
Blomjous B, Abheiden C, Kroese S, van Laar J, Derksen R, Bultink I, Voskuyl A, Lely A , de Boer M, de Vries J, Fritsch-Stork R(2017). OP0310 Pregnancy outcome in women with systemic lupus erythematosus, a multicenter cohort-study. Ann Rheum Dis, 76:184

6
Boh E E (2004). Neonatal lupus erythematosus. Clin Dermatol, 22(2): 125–128

DOI PMID

7
Bramham K, Hunt B J, Germain S, Calatayud I, Khamashta M, Bewley S, Nelson-Piercy C (2010). Pregnancy outcome in different clinical phenotypes of antiphospholipid syndrome. Lupus, 19(1): 58–64

DOI PMID

8
Brkic Z, Corneth O B, van Helden-Meeuwsen C G, Dolhain R J, Maria N I, Paulissen S M, Davelaar N, van Hamburg J P, van Daele P L, Dalm V A, van Hagen P M, Hazes J M, Versnel M A, Lubberts E (2014). T-helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus? Arthritis Res Ther, 16(2): R62

DOI PMID

9
Budde P, Zucht H D, Schulte-Pelkum J, Wirtz D, Rengers P, Vordenbäumen S, Schneider M, Schulz-Knappe P (2017). 267 Novel autoantibodies against the interferon-responsive major vault protein (mvp) in systemic lupus erythmatosus. Lupus Sci Med, 4: doi: 10.1136/lupus-2017-000215.267

10
Chakravarty E F, Colón I, Langen E S, Nix D A, El-Sayed Y Y, Genovese M C, Druzin M L (2005). Factors that predict prematurity and preeclampsia in pregnancies that are complicated by systemic lupus erythematosus. Am J Obstet Gynecol, 192(6): 1897–1904

DOI PMID

11
Chakravarty E F, Nelson L, Krishnan E (2006). Obstetric hospitalizations in the United States for women with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum, 54(3): 899–907

DOI PMID

12
Chamberlain C, Colman P J, Ranger A M, Burkly L C, Johnston G I, Otoul C, Stach C,Zamacona M, Dörner T, Urowitz M, Hiepe F (2017). Repeated administration of dapirolizumab pegol in a randomised phase I study is well tolerated and accompanied by improvements in several composite measures of systemic lupus erythematosus disease activity and changes in whole blood transcriptomic profiles. Ann Rheum Dis, 76(11):1837–1844

13
Clowse M E (2007). Lupus activity in pregnancy. Rheum Dis Clin North Am, 33(2): 237–252, v

DOI PMID

14
Clowse M E, Wallace D J, Weisman M, James A, Criscione-Schreiber L G, Pisetsky D S (2013). Predictors of preterm birth in patients with mild systemic lupus erythematosus. Ann Rheum Dis, 72(9):1536-1539

15
Clowse M E, Magder L S, Petri M (2011). The clinical utility of measuring complement and anti-dsDNA antibodies during pregnancy in patients with systemic lupus erythematosus. J Rheumatol, 38(6):1012–1016

DOI

16
Costa Reis A P, Russo P, Gallucci S, Sullivan K E (2014). A150: Control of Cell Proliferation in Lupus Nephritis: The Role of miRNAs and HER2. Arthritis Rheumatol, 66(S3): S194

DOI

17
de Leeuw K, Bungener L, Roozendaal C, Bootsma H, Stegeman C A(2017). Comment on: Auto-antibodies to double-stranded DNA as biomarker in SLE: comparison of different assays during quiescent and active disease. Rheumatology, 56(11): 2039–2040

DOI

18
Flechsig A, Rose T, Barkhudarova F, Strauss R, Klotsche J, Dähnrich C, Schlumberger W, Enghard P, Burmester G R, Hiepe F, Biesen R (2017). What is the clinical significance of anti-Sm antibodies in systemic lupus erythematosus? A comparison with anti-dsDNA antibodies and C3. Clin Exp Rheumatol, 35(4): 598–606

PMID

19
Font J, Pallares L, Martorell J, Martinez E, Gaya A, Vives J, Ingelmo M (1996). Elevated soluble CD27 levels in serum of patients with systemic lupus erythematosus. Clin Immunol Immunopathol, 81(3): 239–243

DOI PMID

20
Förger F, Matthias T, Oppermann M, Becker H, Helmke K (2004). Clinical significance of anti-dsDNA antibody isotypes: IgG/IgM ratio of anti-dsDNA antibodies as a prognostic marker for lupus nephritis. Lupus, 13(1): 36–44

DOI PMID

21
Freedman B I, Langefeld C D, Andringa K K, Croker J A, Williams A H, Garner N E, Birmingham D J, Hebert L A, Hicks P J, Segal M S, Edberg J C, Brown E E, Alarcón G S, Costenbader K H, Comeau M E, Criswell L A, Harley J B, James J A, Kamen D L, Lim S S, Merrill J T, Sivils K L, Niewold T B, Patel N M, Petri M, Ramsey-Goldman R, Reveille J D, Salmon J E, Tsao B P, Gibson K L, Byers J R, Vinnikova A K, Lea J P, Julian B A, Kimberly R P, and the Lupus Nephritis–End‐Stage Renal Disease Consortium (2014). End-stage renal disease in African Americans with lupus nephritis is associated with APOL1. Arthritis Rheumatol, 66(2): 390–396

DOI PMID

22
Guimarães P M, Macedo Guimarães P, Miglioranza Acavuzzi B, Frizon Alfieri D, Perugini Stadtlober N, Batisti Lozovoy M A, Vissoci Reiche E M, Kaminami Morimoto H, Delicato de Almeida E R, Mayumi Veiga Iriyoda T, Tomimura Costa N, Dichi I, Maes M (2017). 459 Systemic lupus erythematosus and severity of illness are associated with t helper 1 and 17 cytokines profiles together with a lowered il-4 production. Lupus Sci Med, 4:

DOI

23
Guo S, Ge S, Ku M, Shang W, Zeng R, Han M, Xu G, Rong S (2016). Clinical correlation of plasma miR-21, miR-126 and miR-148a in patients with lupus nephritis. Int J Clin Exp Med, 9(2): 2905–U7186

24
Heelan K, Watson R, Collins S M (2013). Neonatal lupus syndrome associated with ribonucleoprotein antibodies. Pediatr Dermatol, 30(4): 416–423

DOI PMID

25
Ho A, Barr S G, Magder L S, Petri M (2001). A decrease in complement is associated with increased renal and hematologic activity in patients with systemic lupus erythematosus. Arthritis Rheum, 44(10): 2350–2357

DOI PMID

26
Huang Q, Chen S S, Li J, Tao S S, Wang M, Leng R X, Pan H F, Ye D Q (2017). miR-210 expression in PBMCs from patients with systemic lupus erythematosus and rheumatoid arthritis. Ir J Med Sci,

DOI

27
Izmirly P M, Halushka M K, Rosenberg A Z, Whelton S, Rais-Bahrami K, Nath D S, Parton H, Clancy R M, Rasmussen S, Saxena A, Buyon J P (2017). Clinical and pathologic implications of extending the spectrum of maternal autoantibodies reactive with ribonucleoproteins associated with cutaneous and now cardiac neonatal lupus from SSA/Ro and SSB/La to U1RNP. Autoimmun Rev, 16(9): 980–983

DOI PMID

28
Kaifu T, Nakamura A (2017). Polymorphisms of immunoglobulin receptors and the effects on clinical outcome in cancer immunotherapy and other immune diseases: a general review. Int Immunol, 29(7): 319–325

DOI PMID

29
Kang S, Fedoriw Y, Brenneman E K, Truong Y K, Kikly K, Vilen B J (2017). BAFF Induces Tertiary Lymphoid Structures and Positions T Cells within the Glomeruli during Lupus Nephritis. J Immunol, 198(7): 2602–2611

DOI PMID

30
Kariuki S N, Ghodke-Puranik Y, Dorschner J M, Chrabot B S, Kelly J A, Tsao B P, Kimberly R P, Alarcón-Riquelme M E, Jacob C O, Criswell L A, Sivils K L, Langefeld C D, Harley J B, Skol A D, Niewold T B (2015). Genetic analysis of the pathogenic molecular sub-phenotype interferon-alpha identifies multiple novel loci involved in systemic lupus erythematosus. Genes Immun, 16(1): 15–23

DOI PMID

31
Keisa L, Boka O, Vitina S, Rezeberga D (2016). New onset of systemic lupus erythematosus during pregnancy. Int J Reprod Contracept Obstet Gynecol, 5(4): 1221–1224

DOI

32
Kim B S, Jung J Y, Jeon J Y, Kim H A, Suh C H (2016a). Circulating hsa-miR-30e-5p, hsa-miR-92a-3p, and hsa-miR-223-3p may be novel biomarkers in systemic lupus erythematosus. HLA, 88(4): 187–193

DOI PMID

33
Kim K J, Baek I W, Yoon C H, Kim W U, Cho C S (2017). Elevated levels of soluble CD40 ligand are associated with antiphospholipid antibodies in patients with systemic lupus erythematosus. Clin Exp Rheumatol, 35(5): 823–830

PMID

34
Kim M Y, Buyon J P, Guerra M M, Rana S, Zhang D, Laskin C A, Petri M, Lockshin M D, Sammaritano L R,Branch D W, Porter T F, Merrill J T, Stephenson M D, Gao Q, Karumanchi S A, Salmon J E(2016b). Angiogenic factor imbalance early in pregnancy predicts adverse outcomes in patients with lupus and antiphospholipid antibodies: results of the PROMISSE study. Am J Obstet Gynecol, 214(1):108.e1–108.e14

35
La Paglia G M C, Leone M C, Lepri G, Vagelli R, Valentini E, Alunno A, Tani C (2017). One year in review 2017: systemic lupus erythematosus. Clin Exp Rheumatol, 35(4): 551–561

PMID

36
Lateef A, Petri M (2013). Managing lupus patients during pregnancy. Best Pract Res Clin Rheumatol, 27(3): 435–447

DOI PMID

37
Lateef A, Petri M (2017). Systemic Lupus Erythematosus and Pregnancy. Rheum Dis Clin North Am, 43(2): 215–226

DOI PMID

38
Lazzaroni M, Andreoli L, Lupoli F, Aggogeri E, Bettiga E , Zatti S, Lojacono A, Ramazzotto F, Fredi M,Tincani A(2016). THU0300 Risk Factors for Adverse Pregnancy Outcome in First-Line Treated Pregnancies in Antiphospholipid Antibodies-Positive Women According To Different Treatment Strategies: Results from Our 30 Years’ Experience Pregnancy Clinic. Ann Rheum Dis, 75:295

39
Lazzaroni M, Andreoli L, Chighizola C B, Ross T D, M Gerosa (2017). OP0046 Risk factors for adverse pregnancy outcome in antiphospholipid antibodies carriers: results from a multicenter italian cohort over 20 years of experience. European Congress of Rheumatology, 70:1–70

40
Le Thi Thuong D, Tieulié N, Costedoat N, Andreu M R, Wechsler B, Vauthier-Brouzes D, Aumaître O, Piette J C (2005). The HELLP syndrome in the antiphospholipid syndrome: retrospective study of 16 cases in 15 women. Ann Rheum Dis, 64(2): 273–278

DOI PMID

41
Linnik M D, Hu J Z, Heilbrunn K R, Strand V, Hurley F L, Joh T, and the LJP 394 Investigator Consortium (2005). Relationship between anti-double-stranded DNA antibodies and exacerbation of renal disease in patients with systemic lupus erythematosus. Arthritis Rheum, 52(4): 1129–1137

DOI PMID

42
Liu E, Zhou Y, Liu Z, Wang L, Zhang Y, Han B, Ma H, Li S (2016). MicroRNA-185 contributes to DNA hypomethylation of CD4+ T cells in pregnant patients with systemic lupus erythematosus by targeting DNA methyltransferase 1. Int J Clin Exp Pathol, 9(8): 8181–8189

43
Liu Y, Xu M, Min X, Wu K, Zhang T, Li K, Xiao S, Xia Y (2017). TWEAK/Fn14 Activation Participates in Ro52-Mediated Photosensitization in Cutaneous Lupus Erythematosus. Front Immunol, 8: 651

DOI PMID

44
Lu J, Kwan B C, Lai F M, Tam L S, Li E K, Chow K M, Wang G, Li P K, Szeto C C (2012). Glomerular and tubulointerstitial miR-638, miR-198 and miR-146a expression in lupus nephritis. Nephrology (Carlton), 17(4): 346–351

DOI PMID

45
Lyn-Cook B D, Xie C, Oates J, Treadwell E, Word B, Hammons G, Wiley K (2014). Increased expression of Toll-like receptors (TLRs) 7 and 9 and other cytokines in systemic lupus erythematosus (SLE) patients: ethnic differences and potential new targets for therapeutic drugs. Mol Immunol, 61(1): 38–43

DOI PMID

46
Mackay F (2017). 345 Deletion of the baff receptor taci fully protects against sle without reduction of b cell numbers and function. Lupus Sci Med, 4: doi:10.1136/lupus-2017-000215.345

47
Mankee A, Petri M, Magder L S (2015). Lupus anticoagulant, disease activity and low complement in the first trimester are predictive of pregnancy loss. Lupus Sci Med, 2(1): e000095

DOI PMID

48
Massenkeil G, Alexander T, Rosen O, Dörken B, Burmester G, Radbruch A, Hiepe F, Arnold R (2016). Long-term follow-up of fertility and pregnancy in autoimmune diseases after autologous haematopoietic stem cell transplantation. Rheumatol Int, 36(11): 1563–1568

DOI PMID

49
McCarthy E M, Smith S, Lee R Z, Cunnane G, Doran M F, Donnelly S, Howard D, O’Connell P, Kearns G, Ní Gabhann J, Jefferies C A (2014). The association of cytokines with disease activity and damage scores in systemic lupus erythematosus patients. Rheumatology (Oxford), 53(9): 1586–1594

DOI PMID

50
Medina G, Florez O I , Montiel Manzano G, Reyes Maldonado E , Cruz Domínguez P, Ortega L O, Saavedra M A, Salinas L J(2015). Jara6 AB0572 Antiphospholipid Antibodies Profile and Thrombosis Recurrence. Ann Rheum Dis, 74 (Suppl 2) :1091.2–1091

51
Mendez B, Saxena A, Buyon J P, Izmirly P M (2014). Neonatal lupus, In: Sammaritano L R, Bermas B L, eds. Contraception and Pregnancy in Patients with Rheumatic Disease. Berlin: Springer verlag. pp. 251–272

52
Molad Y, Borkowski T, Monselise A, Ben-Haroush A, Sulkes J, Hod M, Feldberg D, Bar J (2005). Maternal and fetal outcome of lupus

53
Moroni G, Ponticelli C (2016). Pregnancy in women with systemic lupus erythematosus (SLE). Eur J Intern Med, 32: 7–12

DOI PMID

54
Nasef N, Hafez M, Bakr A (2014). Neonatal lupus erythematosus. J Neonatol Clin Pediatr, . 77(2): 82–86

55
Palatinus A, Adams M (2009).Thrombosis in systemic lupus erythematosus. Semin Thromb Hemost. 35(7): 621–629

56
Papp G, Chen J Q, Pόliska S, Szabό K, Tarr T, Bá lint B L, Szodoray P, Zeher M(2017). AB0137 Alterations in microrna expression profiles in primary sjÖgren9s syndrome and systemic lupus erythematosus. Ann Rheum Dis,76:1094–1095

57
Pauley K M, Stewart C M, Gauna A E, Dupre L C, Kuklani R, Chan A L, Pauley B A, Reeves W H, Chan E K, Cha S (2011). Altered miR-146a expression in Sjögren’s syndrome and its functional role in innate immunity. Eur J Immunol, 41(7): 2029–2039

DOI PMID

58
Perez-Sanchez C, Aguirre M A, Ruiz-Limon P, Abalos-Aguilera M C, Arias-de la Rosa I, Barbarroja N, Jimenez-Gomez Y, Segui P,Collantes-Estevez E, Gonzalez-Reyes J A, Villalba J M, Cuadrado M J, Lopez-Pedrera C(2017). AB0127 ANTI-DS-DNA antibodies regulate atherothrombosis in systemic lupus erythematosus through the induction of netosis, inflammation and endothelial activation., BMJ Publishing Group Ltd.

59
Perricone C, Ciccacci C, Ceccarelli F, Cipriano E, Alessandri C, Spinelli F R, Rufini S,Politi C,Latini A, Novelli G, Valesini G, Borgiani P , Conti F (2016). AB0004 polymorphisms in genes in the IL-17 pathway and B cell mediated immune response modulate the development of specific autoimmune manifestations in systemic lupus erythematosus. Ann Rheum Dis,75: 898

60
Pickering M C, Walport M J (2000). Links between complement abnormalities and systemic lupus erythematosus. Rheumatology (Oxford), 39(2): 133–141

DOI PMID

61
Qian J, Nan ( S 2017). 307 The pathogenic mechanisms of systemic lupus erythematosus associated genes pnp, plekhf2 and ankrd44. Lupus Sci Med, 4: doi:10.1136/lupus-2017-000215.307

62
Ramezani M, Hashemi B S, Khazaei S, Rezaei M, Ebrahimi A, Sadeghi M (2017). Diagnostic value of immunohistochemistry staining of Bcl-2, CD34, CD20 and CD3 for distinction between discoid lupus erythematosus and lichen planus in the skin. Indian J Pathol Microbiol, 60(2): 172–176

DOI PMID

63
Ray D, Hailow S, Strickland F, Orlowski R, Marder W, McCune W J, Somer E C, (2016). CD70 methylation of a regulatory region increases with age in lupus patients., J Immnol, 196(Suppl.): 1876

64
Reis P C, Maurer K, Schanberg L, Burnham J M , von Scheven E, O'Neil K, Klein Gitelman M ,Petri M ,Sullivan K E(2017). THU0490 Multicentre study of lupus nephritis urinary biomarkers in adult and paediatric patients. Ann Rheum Dis, 76: 391–392

65
Sammaritano L R (2017). Management of systemic lupus erythematosus during pregnancy. Annu Rev Med, 68(1): 271–285

DOI PMID

66
Sawalha A H, Wang L, Nadig A, Somers E C, McCune W J, Hughes T, Merrill J T, Scofield R H, Strickland F M, Richardson B, and the Michigan Lupus Cohort (2012). Sex-specific differences in the relationship between genetic susceptibility, T cell DNA demethylation and lupus flare severity. J Autoimmun, 38(2-3): J216–J222

DOI PMID

67
Shimada H, Kanenishi K, Kameda T, Izumikawa M, Nakashima S, Ozaki H, Wakiya R, Kondo A ,Kadowaki N,H Dobashi(2017). FRI0704 Analysis of risk factor for pregnancy outcomes in 142 pregnancies complicated with connective tissue disease. Ann Rheum Dis, 76:757

68
Sitrin J, Suto E, Wuster A, Eastham-Anderson J, Kim J M, Austin C D, Lee W P, Behrens T W (2017). The Ox40/Ox40 Ligand Pathway Promotes Pathogenic Th Cell Responses, Plasmablast Accumulation, and Lupus Nephritis in NZB/W F1 Mice. J Immunol, 199(4): 1238–1249

DOI PMID

69
Steri M, Orrù V, Idda M L, Pitzalis M, Pala M, Zara I, Sidore C, Faà V, Floris M, Deiana M, Asunis I, Porcu E, Mulas A, Piras M G, Lobina M, Lai S, Marongiu M, Serra V, Marongiu M, Sole G, Busonero F, Maschio A, Cusano R, Cuccuru G, Deidda F, Poddie F, Farina G, Dei M, Virdis F, Olla S, Satta M A, Pani M, Delitala A, Cocco E, Frau J, Coghe G, Lorefice L, Fenu G, Ferrigno P, Ban M, Barizzone N, Leone M, Guerini F R, Piga M, Firinu D, Kockum I, Lima Bomfim I, Olsson T, Alfredsson L, Suarez A, Carreira P E, Castillo-Palma M J, Marcus J H, Congia M, Angius A, Melis M, Gonzalez A, Alarcón Riquelme M E, da Silva B M, Marchini M, Danieli M G, Del Giacco S, Mathieu A, Pani A, Montgomery S B, Rosati G, Hillert J, Sawcer S, D’Alfonso S, Todd J A, Novembre J, Abecasis G R, Whalen M B, Marrosu M G, Meloni A, Sanna S, Gorospe M, Schlessinger D, Fiorillo E, Zoledziewska M, Cucca F (2017). Overexpression of the cytokine BAFF and autoimmunity risk. N Engl J Med, 376(17): 1615–1626

DOI PMID

70
Sun Y, Peng R, Peng H, Liu H, Wen L, Wu T, Yi H, Li A, Zhang Z (2016). miR-451 suppresses the NF-kappaB-mediated proinflammatory molecules expression through inhibiting LMP7 in diabetic nephropathy. Mol Cell Endocrinol, 433: 75–86

DOI PMID

71
Tangtanatakul P, Thammasate B, Jacquet A, Reantragoon R, Pisitkun T,Avihingsanon Y, Leelahavanichkul A, Hirankarn N (2017). 322 Down-regulation of mir-10a induces il-8 in human mesangial cells stimulated with anti-dsdna igg antibodies. Lupus Sci Med, 4: doi:10.1136/lupus-2017-000215.322

72
Teh C L, Wan S A, Cheong Y K, Ling G R (2016). Systemic lupus erythematosus pregnancies: ten-year data from a single centre in Malaysia. Lupus, 26(2): 218–223

DOI PMID

73
Testa U, Pelosi E, Castelli G, Labbaye C (2017). miR-146 and miR-155: Two Key Modulators of Immune Response and Tumor Development. Non-Coding RNA, 3(3): 22

DOI

74
Ünlü O, Zuily S, Erkan D ( 2016 ). The clinical significance of antiphospholipid antibodies in systemic lupus erythematosus. Euro J Rheum, 3(2): 75

75
Vinet É, Pineau C A, Clarke A E, Fombonne É, Platt R W, Bernatsky S (2014). Neurodevelopmental disorders in children born to mothers with systemic lupus erythematosus. Lupus, 23(11): 1099–1104

DOI PMID

76
Wang G, Tam L S, Kwan B C, Li E K, Chow K M, Luk C C, Li P K, Szeto C C (2012a). Expression of miR-146a and miR-155 in the urinary sediment of systemic lupus erythematosus. Clin Rheumatol, 31(3): 435–440

DOI PMID

77
Wang G, Tam L S, Li E K, Kwan B C, Chow K M, Luk C C, Li P K, Szeto C C (2010). Serum and urinary cell-free MiR-146a and MiR-155 in patients with systemic lupus erythematosus. J Rheumatol, 37(12): 2516–2522

DOI PMID

78
Wang H, Peng W, Ouyang X, Li W, Dai Y (2012b). Circulating microRNAs as candidate biomarkers in patients with systemic lupus erythematosus. Transl Res, 160(3): 198–206

DOI PMID

79
Wang Z, Chang C, Peng M, Lu Q (2017). Translating epigenetics into clinic: focus on lupus. Clin Epigenetics, 9(1): 78

DOI PMID

80
Yelnik C M, Laskin C A, Porter T F, Branch D W, Buyon J P, Guerra M M, Lockshin M D, Petri M, Merrill J T, Sammaritano L R, Kim M Y, Salmon J E (2016). Lupus anticoagulant is the main predictor of adverse pregnancy outcomes in aPL-positive patients: validation of PROMISSE study results. Lupus Sci Med, 3(1): e000131

DOI PMID

81
Yin H, Lu Q (2014). Histone Demethylase Jmjd3 Regulates Cd11a Expression In Lupus T Cells By Changing Histone H3k27 Tri-methylation Level. J Dermatol, 41: 29

PMID

82
Zeng J, Wu H, Zhao M, Q Lu(2017). Novel biomarkers for systemic lupus erythematosus. Biomark Med, https://doi.org/10.2217/bmm-2016-0379.

83
Zhang Y, Zhao M, Sawalha A H, Richardson B, Lu Q (2013). Impaired DNA methylation and its mechanisms in CD4(+)T cells of systemic lupus erythematosus. J Autoimmun, 41: 92–99

DOI PMID

84
Zola H, Swart B ( 2016). CD Markers. Encyclopedia of Immunotoxicology, 146–150

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