title: Pentraxin 3 Is Closely Associated With Tubulointerstitial Injury in Lupus Nephritis: A Large Multicenter Cross-Sectional Study.
abstract: Lupus nephritis always elicits immune inflammatory tissue damages in kidney. Pentraxin 3 (PTX3), mainly produced at inflammatory sites, is known to be involved in the regulation of the innate immunity system. The aim of this study was to investigate the serum and urine levels of PTX3, and the expression of PTX3 in renal tissues in lupus nephritis patients from a large Chinese cohort.The study used cross-sectional survey and 288 active lupus nephritis patients, including discovery cohort and validation cohort, 115 systemic lupus erythematosus (SLE) patients without clinical renal involvement and 46 healthy controls were enrolled. Serum and urine PTX3 were screened by enzyme-linked immunosorbent assay (ELISA). The renal deposition of PTX3 was detected by immunohistochemistry and immunofluorescence.The average level of serum PTX3 in the discovery cohort of lupus nephritis was significantly higher than that in nonrenal involvement SLE group and normal controls (P < 0.001, P < 0.001, respectively), which was confirmed by the validation cohort. Serum PTX3 levels of 15 lupus nephritis patients in remission decreased significantly compared with that in active phase. Serum PTX3 levels were significantly higher in patients with hematuria (P = 0.014), leucocyturia (P = 0.002), acute renal failure (P = 0.001), and nephrotic syndrome (P = 0.036). There were significant correlations between serum PTX3 levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, serum creatinine value, renal pathological activity indices, and serum complement 3 (C3) in active lupus nephritis patients. The urinary PTX3 levels were significantly higher in active lupus nephritis patients compared with patients in remission and normal controls (P = 0.011, P = 0.008, respectively). There were significant associations between urinary PTX3 levels and multiple indices of tubulointerstitial lesions, including urinary KIM-1 (r = 0.368, P = 0.016), neutrophil gelatinase-associated lipocalin (NGAL) (r = 0.320, P = 0.039), microalbumin (r = 0.621, P = 0.003), transferring (r = 0.451, P = 0.040) levels and renal pathological indices scores, especially interstitial inflammation (r = 0.349, P = 0.025) in active lupus nephritis patients. A significant correlation was found between serum and urine PTX3 levels (r = 0.431, P = 0.006). PTX3 staining was mainly observed in tubulointerstitial areas of patients with lupus nephritis, and immunofluorescence study showed that PTX3 could colocalize with fibroblast in interstitium.Circulating and local PTX3 levels were significantly increased in patients with active lupus nephritis and might be a biomarker for the disease progression, especially of tubulointerstitial injury.
authors.affiliation: From the Renal Division, Department of Medicine, Peking University First Hospital, Beijing, P.R. China (YP, YT, FY, M-HZ); Institute of Nephrology, Peking University, Beijing, P.R. China (YP, YT, FY, M-HZ); Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, P.R. China (YP, YT, FY, M-HZ); Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, P.R. China (YP, YT, FY, M-HZ); Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Beijing, P.R. China (YL); Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China (YL); Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, P.R. China (YL); Renal Division, Jing Dong Yu Mei Traditional Chinese Medicine and Western Medicine Integrative Kidney Disease Hospital, Hebei, P.R. China (JZ); Department of Nephrology, Anyang District Hospital, Henan, P.R. China (YG); Department of Nephrology, First Affiliated Hospital of Henan University of Science and Technology, Henan, P.R. China (ZG); Department of Nephrology, Beijing General Hospital of Armed Police Forces, Beijing, P.R. China (CZ); Department of Nephrology, Peking University International Hospital, Beijing, P.R. China (FY); and Peking-Tsinghua Center for Life Sciences, Beijing, P.R. China ( M-HZ).
authors.forename: Yun
authors.initials: Y
authors.lastname: Pang
authors.forename: Ying
authors.initials: Y
authors.lastname: Tan
authors.forename: Yongzhe
authors.initials: Y
authors.lastname: Li
authors.forename: Jianchun
authors.initials: J
authors.lastname: Zhang
authors.forename: Yongbing
authors.initials: Y
authors.lastname: Guo
authors.forename: Zhiling
authors.initials: Z
authors.lastname: Guo
authors.forename: Chengying
authors.initials: C
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Yu
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Zhao
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002097:C-Reactive Protein / Q000032:analysis*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D008181:Lupus Nephritis / Q000097:blood / Q000473:pathology* / Q000652:urine; D008297:Male; D008854:Microscopy, Electron; D009395:Nephritis, Interstitial / Q000097:blood / Q000473:pathology / Q000652:urine; D000683:Serum Amyloid P-Component / Q000032:analysis*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000099153:Pentraxins
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein; D053583:Interleukin-1beta; D000683:Serum Amyloid P-Component; D014409:Tumor Necrosis Factor-alpha; D000099153:Pentraxins
references.citation: Lupus. 2013 Dec;22(14):1446-54
references.pmid: 24097970
references.citation: J Am Soc Nephrol. 2005 Nov;16(11):3281-94
references.pmid: 16192422
references.citation: J Histochem Cytochem. 2008 May;56(5):517-29
references.pmid: 18285351
references.citation: Proc Natl Acad Sci U S A. 2014 Sep 30;111(39):14193-8
references.pmid: 25225370
references.citation: Kidney Int. 2009 Aug;76(3):307-17
references.pmid: 19404274
references.citation: Arthritis Rheum. 1989 Sep;32(9):1107-18
references.pmid: 2775320
references.citation: Kidney Int. 2004 Feb;65(2):521-30
references.pmid: 14717922
references.citation: J Immunol. 2011 Feb 1;186(3):1849-60
references.pmid: 21187439
references.citation: Arthritis Rheum. 1997 Sep;40(9):1725
references.pmid: 9324032
references.citation: J Biol Chem. 1992 Nov 5;267(31):22190-7
references.pmid: 1429570
references.citation: Arthritis Rheum. 2012 Mar;64(3):854-65
references.pmid: 21989653
references.citation: Clin J Am Soc Nephrol. 2010 Nov;5(11):1954-9
references.pmid: 20813857
references.citation: J Pathol. 2010 Jan;220(1):7-16
references.pmid: 19921716
references.citation: Arthritis Rheum. 2003 Oct;48(10):2888-97
references.pmid: 14558095
references.citation: Arthritis Rheum. 2001 Dec;44(12):2841-50
references.pmid: 11762945
references.citation: Mod Rheumatol. 2014 Jan;24(1):78-85
references.pmid: 24261762
references.citation: Blood. 2000 Dec 15;96(13):4300-6
references.pmid: 11110705
references.citation: J Immunol. 2012 May 1;188(9):4568-80
references.pmid: 22467656
references.citation: Nature. 2002 Nov 14;420(6912):182-6
references.pmid: 12432394
references.citation: Eur J Immunol. 2003 Feb;33(2):465-73
references.pmid: 12645945
references.citation: Medicine (Baltimore). 2003 Sep;82(5):299-308
references.pmid: 14530779
references.citation: Arthritis Care Res (Hoboken). 2011 Jun;63(6):865-74
references.pmid: 21309006
references.citation: Kidney Int. 1994 Feb;45(2):544-50
references.pmid: 8164443
references.citation: Nat Med. 1999 Jun;5(6):694-7
references.pmid: 10371509
references.citation: J Immunol. 2003 Feb 1;170(3):1466-72
references.pmid: 12538709
references.citation: Arthritis Rheum. 1992 Jun;35(6):630-40
references.pmid: 1599520
references.citation: Semin Arthritis Rheum. 2009 Aug;39(1):38-54
references.pmid: 18614204
references.citation: Arthritis Res Ther. 2009 Oct 14;11(5):R154
references.pmid: 19828047
references.citation: Circulation. 2000 Aug 8;102(6):636-41
references.pmid: 10931803
references.citation: Kidney Int. 1984 Apr;25(4):689-95
references.pmid: 6482173
references.citation: Autoimmun Rev. 2008 May;7(5):345-51
references.pmid: 18486920
references.citation: Ann Rheum Dis. 2014 Feb;73(2):475-6
references.pmid: 24092416
references.citation: J Exp Med. 2000 Nov 6;192(9):1353-64
references.pmid: 11067883
references.citation: Arthritis Rheum. 2006 Mar;54(3):986-91
references.pmid: 16508993
references.citation: Kidney Int. 2010 May;77(9):820-9
references.pmid: 20182417
references.citation: J Am Soc Nephrol. 2015 Feb;26(2):379-89
references.pmid: 25012167
references.citation: J Immunol. 1993 Mar 1;150(5):1804-12
references.pmid: 7679696
references.citation: Arthritis Rheum. 2007 May;56(5):1569-78
references.pmid: 17469139
references.citation: Clin Exp Immunol. 2000 Jan;119(1):196-202
references.pmid: 10606983
references.citation: J Clin Immunol. 2008 Jan;28(1):1-13
references.pmid: 17828584
references.citation: Arthritis Rheumatol. 2014 Dec;66(12):3359-70
references.pmid: 25306868
references.citation: Arthritis Rheum. 2004 Aug;50(8):2667-74
references.pmid: 15334483
references.citation: Autoimmun Rev. 2006 Jul;5(6):383-8
references.pmid: 16890891
references.citation: Arthritis Care Res (Hoboken). 2010 Mar;62(3):378-85
references.pmid: 20391484
references.citation: J Biol Chem. 1997 Dec 26;272(52):32817-23
references.pmid: 9407058