Journal of Peking University (Health Sciences) ›› 2022, Vol. 54 ›› Issue (6): 1094-1098. doi: 10.19723/j.issn.1671-167X.2022.06.006

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Characteristics of serum autoantibodies in patients with lupus nephritis and tubulointerstitial damage

Lu ZHANG1,Cheng CHEN1,Mei-ting WENG1,Ai-ping ZHENG2,Mei-ling SU3,Qing-wen WANG1,Yue-ming CAI1,*()   

  1. 1. Department of Rheumatology & Immunology, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong, China
    2. Department of Medical Pathology, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong, China
    3. Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong, China
  • Received:2022-08-16 Online:2022-12-18 Published:2022-12-19
  • Contact: Yue-ming CAI E-mail:cyueming@163.com
  • Supported by:
    the Science and Technology Program for Basic Research in Shenzhen(JCYJ20190809095811254);Project of Shenzhen Municipal Health Commission(SZXJ2017046)

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Abstract:

Objective: To observe the tubulointerstitial damage (TID) in lupus nephritis (LN) and investigate the relationship between autoantibodies and TID in lupus nephritis. Methods: This cross-sectional study was conducted in a comprehensive tertiary hospital in Peking University Shenzhen Hospital. From March 2012 to July 2021, LN patients who performed renal biopsy were enrolled in the study. Clinical, laboratory and pathology data were collected. We classified the patients into none-or-mild group and moderate-to-severe groups according to the severity of interstitial fibrosis (IF) /tubular atrophy (TA) or tubulointerstitial inflammation (TII). The t test, U test and Chi-square test were used for statistical analysis as appropriate. Results: A total of 226 patients were included, of who 190 (84%) were female with a median age of 32 (26, 39) years. 89% (201/226) of the patients who pathologically proved to be proliferative LN by renal biopsy. The frequency of moderate-to-severe TII and moderate-to-severe IF/TA was 30% (67/226) and 34% (76/226) respectively. For autoantibodies, the patients with moderate-to-severe TII had a lower rate of positive serum anti-ribonucleoprotein (anti-RNP) antibodies than the patients with none-or-mild TII (34% vs. 51%), and moderate-to-severe IF/TA had a lower rate of positive anti-ribosomal P protein (anti-P) antibodies than patients with none-or-mild IF/TA (19% vs. 33%). For other clinical indicators, the patients with moderate-to-severe TII and moderate-to-severe IF/TA were more often combined with proliferative LN, hypertension and anemia than the patients with none-or-mild TII and none-or-mild IF/TA, respectively. The patients with moderate-to-severe TII had higher serum creatinine values and lower glomerular filtration rates than the patients with none-or-mild TII. The patients with moderate-to-severe IF/TA had higher serum creatinine values, and lower glomerular filtration rates than the patients with none-or-mild IF/TA. Conclusion: In patients with LN in Southern China, anti-RNP antibodies and anti-P antibodies may be potential protective factors for TII and IF/TA, respectively. More studies are needed to identify the risk factors of lupus patients with TID and investigate the correlation between autoantibodies and TID, which are critical for developing better preventive and therapeutic strategies to improve the survival rate of LN.

Key words: Lupus nephritis, Tubulointerstitial damage, Autoantibodies, Anti-ribonucleoprotein antibody, Anti-ribosomal P protein antibody

CLC Number: 

  • R593.24

Table 1

Baseline demographic, clinical characteristic for the study patients in the overall sample and stratified by TI or IF/TA"

Items Total (n=226) TII IF/TA
None-or-mild (n=159) Moderate-to-severe (n=67) P None-or-mild (n=150) Moderate-to-severe (n=76) P
Demographics
  Female 190 (84) 134 (84) 56 (84) 0.999 128 (85) 62 (82) 0.590
  Age/years 32 (26, 39) 31 (27, 38) 32 (26, 43) 0.510 31 (26, 37) 32 (26, 45) 0.200
Clinical characteristic
  Duration/months 14 (2, 72) 12 (2, 54) 36 (3, 96) 0.110 12 (2, 57) 24 (2, 87) 0.170
  Hypertension 72 (32) 33 (21) 39 (58) < 0.001 34 (23) 38 (50) < 0.001
Histology characteristic
  Proliferative 201 (89) 136 (86) 65 (97) 0.023 128 (85) 73 (96) 0.028
  Moderate-to-severe IF/TA 76 (34) 19 (12) 57 (85) < 0.001
  Moderate-to-severe TII 67 (30) 10 (7) 57 (75) < 0.001
Autoantibody (positive)
  Anti-dsDNA 111 (53) 78 (52) 33 (54) 0.938 76 (54) 35 (50) 0.660
  Anti-RNP 94 (46) 74 (51) 20 (34) 0.032 68 (50) 26 (37) 0.098
  Anti-Sm 54 (27) 40 (27) 14 (25) 0.815 36 (27) 18 (26) 0.999
  Anti-SSA 135 (66) 100 (69) 35 (59) 0.275 95 (70) 40 (57) 0.082
  Anti-SSB 31 (15) 20 (14) 11 (19) 0.497 18 (13) 13 (19) 0.431
  ANuA 71 (35) 49 (34) 22 (37) 0.730 46 (34) 25 (36) 0.937
  AHA 67 (33) 49 (34) 18 (31) 0.797 45 (33) 22 (31) 0.906
  Anti-P 57 (28) 45 (31) 12 (20) 0.179 44 (33) 13 (19) 0.049
  APL 27 (16) 20 (17) 7 (15) 0.887 19 (18) 8 (14) 0.680
  ANCA 22 (12) 12 (9) 10 (17.9) 0.084 11 (9) 11 (18) 0.068
Laboratory parameters
  eGFR/[mL/(min·1.73 m2)] 81.7 (51.1, 113.5) 96.2 (70.0, 123.4) 39.1 (24.1, 59.8) < 0.001 97.2 (68.9, 124.5) 43.9 (25.2, 80.5) < 0.001
  Serum creatinine/(μmol/L) 79.5 (57.5, 125.0) 67.5 (54.2, 90.0) 145.5 (102.5, 292.0) < 0.001 66.1 (54.0, 91.7) 134.5 (85.8, 218.8) < 0.001
  Lower C3 158 (72) 113 (72) 45 (73) 0.999 104 (71) 54 (75) 0.618
  Lower C4 94 (44) 71 (46) 23 (38) 0.334 65 (45) 29 (41) 0.746
  Hemoglobin/(g/L) 101.5±25.8 105.7±24.7 91.7±25.7 < 0.001 105.7±25.0 93.2±25.4 < 0.001
  Spot urine protein/creatinine/(g/g) 3.0 (1.4, 5.6) 2.8 (1.0, 5.0) 3.5 (2.0, 5.7) 0.063 2.9 (1.0, 4.7) 3.5 (2.0, 5.8) 0.081
Medications
  Treatment-naive 90 (42) 74 (49) 16 (25) 0.002 67 (47) 23 (32) 0.039
1 Kiriakidou M , Ching CL . Systemic lupus erythematosus[J]. Ann Intern Med, 2020, 172 (11): ITC81- ITC96.
doi: 10.7326/AITC202006020
2 Fanouriakis A , Kostopoulou M , Cheema K , et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis[J]. Ann Rheum Dis, 2020, 79 (6): 713- 723.
doi: 10.1136/annrheumdis-2020-216924
3 Rijnink E , Teng Y , Wilhelmus S , et al. Clinical and histopathologic characteristics associated with renal outcomes in lupus nephritis[J]. Clin J Am Soc Nephrol, 2017, 12 (5): 734- 743.
doi: 10.2215/CJN.10601016
4 Broder A , Mowrey WB , Khan HN , et al. Tubulointerstitial da-mage predicts end stage renal disease in lupus nephritis with preserved to moderately impaired renal function: A retrospective cohort study[J]. Semin Arthritis Rheum, 2018, 47 (4): 545- 551.
doi: 10.1016/j.semarthrit.2017.07.007
5 Yu F , Wu LH , Tan Y , et al. Tubulointerstitial lesions of patients with lupus nephritis classified by the 2003 International Society of Nephrology and Renal Pathology Society system[J]. Kidney Int, 2010, 77 (9): 820- 829.
doi: 10.1038/ki.2010.13
6 Olsen NJ , Karp DR . Autoantibodies and SLE: The threshold for disease[J]. Nat Rev Rheumatol, 2014, 10 (3): 181- 186.
doi: 10.1038/nrrheum.2013.184
7 Londoño Jimenez A , Mowrey WB , Putterman C , et al. Brief report: Tubulointerstitial damage in lupus nephritis: A comparison of the factors associated with tubulointerstitial inflammation and renal scarring[J]. Arthritis Rheumatol, 2018, 70 (11): 1801- 1806.
doi: 10.1002/art.40575
8 Hong R , Xu D , Hsieh E , et al. Factors associated with renal involvement in primary Sjögren's syndrome: A meta-analysis[J]. Front Med (Lausanne), 2020, 7, 614482.
9 Pan HF , Fang XH , Wu GC , et al. Anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus and lupus nephritis[J]. Inflammation, 2008, 31 (4): 260- 265.
doi: 10.1007/s10753-008-9073-3
10 Shi ZR , Cao CX , Tan GZ , et al. The association of serum anti-ribosomal P antibody with clinical and serological disorders in systemic lupus erythematosus: A systematic review and meta-analysis[J]. Lupus, 2015, 24 (6): 588- 596.
doi: 10.1177/0961203314560003
11 Hochberg MC . Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus[J]. Arthritis Rheum, 1997, 40 (9): 1725.
12 Petri M , Orbai A , Alarcón G , et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus[J]. Arthritis Rheum, 2012, 64 (8): 2677- 2686.
doi: 10.1002/art.34473
13 Weening J , D'Agati V , Schwartz M , et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited[J]. J Am Soc Nephrol, 2004, 15 (2): 241- 250.
doi: 10.1097/01.ASN.0000108969.21691.5D
14 Gomes MF , Mardones C , Xipell M , et al. The extent of tubulo-interstitial inflammation is an independent predictor of renal survi-val in lupus nephritis[J]. J Nephrol, 2021, 34 (6): 1897- 1905.
doi: 10.1007/s40620-021-01007-z
15 Leatherwood C , Speyer CB , Feldman CH , et al. Clinical characteristics and renal prognosis associated with interstitial fibrosis and tubular atrophy (IFTA) and vascular injury in lupus nephritis biopsies[J]. Semin Arthritis Rheum, 2019, 49 (3): 396- 404.
doi: 10.1016/j.semarthrit.2019.06.002
16 Wilson PC , Kashgarian M , Moeckel G . Interstitial inflammation and interstitial fibrosis and tubular atrophy predict renal survival in lupus nephritis[J]. Clin Kidney J, 2018, 11 (2): 207- 218.
doi: 10.1093/ckj/sfx093
17 Austin HA , Muenz LR , Joyce KM , et al. Diffuse proliferative lupus nephritis: identification of specific pathologic features affecting renal outcome[J]. Kidney Int, 1984, 25 (4): 689- 695.
doi: 10.1038/ki.1984.75
18 Migliorini P , Baldini C , Rocchi V , et al. Anti-Sm and anti-RNP antibodies[J]. Autoimmunity, 2005, 38 (1): 47- 54.
doi: 10.1080/08916930400022715
19 Carpintero M , Martinez L , Fernandez I , et al. Diagnosis and risk stratification in patients with anti-RNP autoimmunity[J]. Lupus, 2015, 24 (10): 1057- 1066.
doi: 10.1177/0961203315575586
20 Bastian H , Roseman J , Mcgwin G , et al. Systemic lupus erythematosus in three ethnic groups. Ⅻ. Risk factors for lupus nephritis after diagnosis[J]. Lupus, 2002, 11 (3): 152- 160.
doi: 10.1191/0961203302lu158oa
21 Choi M , Fitzpatrick R , Buhler K , et al. A review and meta-analysis of anti-ribosomal P autoantibodies in systemic lupus erythematosus[J]. Autoimmun Rev, 2020, 19 (3): 102463.
doi: 10.1016/j.autrev.2020.102463
22 Kang J , Park D , Choi S , et al. Protective role of anti-ribosomal P antibody in patients with lupus nephritis[J]. Int J Rheum Dis, 2019, 22 (5): 913- 920.
doi: 10.1111/1756-185X.13517
23 Tzioufas A , Tzortzakis N , Panou-pomonis E , et al. The clinical relevance of antibodies to ribosomal-P common epitope in two targeted systemic lupus erythematosus populations: A large cohort of consecutive patients and patients with active central nervous system disease[J]. Ann Rheum Dis, 2000, 59 (2): 99- 104.
doi: 10.1136/ard.59.2.99
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