狼疮肾炎患者肾小管间质损伤的自身抗体特征

doi:10.19723/j.issn.1671-167X.2022.06.006

摘要/Abstract

摘要：

目的: 观察狼疮肾炎(lupus nephritis，LN)肾小管间质损伤(tubulointerstitial damage，TID)情况及自身抗体与LN患者TID的关系。方法: 回顾性收集2012年3月1日至2021年7月31日就诊于北京大学深圳医院且经肾脏活组织检查证实为LN的患者，收集患者的病历资料及临床数据，按肾小管间质炎症(tubulointerstitial inflammation，TII)及肾小管间质瘢痕形成(即间质纤维化和肾小管萎缩，interstitial fibrosis/tubular atrophy，IF/TA)的情况分为中重度组及无或轻度组。采用t检验、Mann-Whitney U检验和卡方检验分析患者临床指标、自身抗体与TII或IF/TA的关系。结果: 共纳入226例患者，中位年龄32(26，39)岁，201例(89%)患者为增殖型LN，中重度TII和中重度IF/TA分别为67例(30%)和76例(34%)。自身抗体方面，中重度TII患者比无或轻度TII患者血清抗RNP抗体阳性率低(34% vs. 51%)，中重度IF/TA比无或轻度IF/TA患者抗核糖体P蛋白(anti-ribosomal P protein，anti-P)抗体阳率低(19% vs. 33%)。其它临床指标方面，与无或轻度TII患者相比，中重度TII患者增殖型LN占比更高，血清肌酐值更高，肾小球滤过率更低，且合并高血压和贫血更多，既往无糖皮质激素和免疫抑制药物使用史的初治患者更少；IF/TA以上临床指标结果与TII一致。结论: 抗RNP抗体和anti-P抗体可能分别是TII和IF/TA的潜在保护因素，需要更多的研究来探讨自身抗体与TID的关系，以制定更好的预防和治疗策略，进而最终改善LN患者的生存率。

关键词: 狼疮肾炎, 肾小管间质损伤, 自身抗体, 抗核糖核蛋白抗体, 抗核糖体P蛋白抗体

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

中图分类号:

R593.24

张璐,陈澄,翁梅婷,郑爱萍,苏美玲,王庆文,蔡月明. 狼疮肾炎患者肾小管间质损伤的自身抗体特征[J]. 北京大学学报（医学版）, 2022, 54(6): 1094-1098.

Lu ZHANG,Cheng CHEN,Mei-ting WENG,Ai-ping ZHENG,Mei-ling SU,Qing-wen WANG,Yue-ming CAI. Characteristics of serum autoantibodies in patients with lupus nephritis and tubulointerstitial damage[J]. Journal of Peking University (Health Sciences), 2022, 54(6): 1094-1098.

图/表 1

表1

按TII和IF/TA分层的患者基线特征和临床特征"

Items	Total (n=226)	TII			IF/TA
Items	Total (n=226)	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

表1

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