收稿日期: 2023-07-25
网络出版日期: 2024-03-26
基金资助
国家自然科学基金青年基金资助项目(82102470)
Association of anti⁃neutrophil cytoplasmic antibodies with the disease activity in patients with systemic lupus erythematosus
Received date: 2023-07-25
Online published: 2024-03-26
目的 探讨中性粒细胞胞浆抗体（anti-neutrophil cytoplasmic antibody， ANCA）在系统性红斑狼疮（systemic lupus erythematosus， SLE）患者疾病活动中的作用，为临床诊疗提供实验室依据。 方法 将1 025例SLE患者纳入本研究，并依据系统性红斑狼疮疾病活动指数（systemic lupus erythematosus disease activity index， SLEDAI）将其分为非活动组（n = 750）和活动组（n = 275）。记录并比较两组患者的人口学特征、临床症状、自身抗体、常规实验室检查、细胞因子和肾脏病理学等指标。 结果 活动组患者具有肾、肺、皮肤、关节炎表现的发生率明显高于非活动组（均P < 0.05）。所有患者均进行了ANCA检测，核周型ANCA（perinuclear ANCA， p-ANCA）是最主要的核型，且与疾病的活动状态显著相关（P < 0.05）。对两组患者的自身抗体进行分析，结果显示，对髓过氧化物酶（myeloperoxidase， MPO）有反应的患者有25例，所有患者对蛋白酶3（proteinase 3， PR3）均无反应；此外，两组之间的抗双链DNA（double-stranded DNA， dsDNA）抗体、抗核小体抗体的差异有统计学意义（P < 0.05）。与非活动组相比，活动组p-ANCA+的患者血清β2-微球蛋白（beta-2-microglobulin，β2-MG）显著升高、抗dsDNA抗体滴度及SLEDAI评分明显增加；相反，白蛋白、C3和C4水平显著降低（P < 0.05）。同时，p-ANCA与IL-6水平明显相关，且IL-6水平随SLEDAI的增加而显著增加。此外，p-ANCA阳性的患者更易于发生狼疮性肾炎，但与肾脏病理无关。 结论 在SLE患者中，p-ANCA的出现表明了更严重的疾病活动状态。
关键词： 抗中性粒细胞胞浆抗体; 系统性红斑狼疮; 白细胞介素6; 核周型中性粒细胞胞浆抗体; 系统性红斑狼疮疾病活动指数
宋萧怡 , 许程洁 , 张航烽 , 王甲甲 . 抗中性粒细胞胞浆抗体与系统性红斑狼疮患者疾病活动度的相关性[J]. 实用医学杂志, 2024 , 40(5) : 658 -663 . DOI: 10.3969/j.issn.1006-5725.2024.05.012
Objective To investigate the clinical significance of ANCA in the disease activity of patients with SLE. Methods A total of 1 025 SLE patients were recruited and were divided into inactive and active groups according to SLEDAI score. Demographic characteristics， clinical symptoms， autoantibodies， routine laboratory tests and renal pathology were also recorded and compared between the two groups. Results All patients were divided into inactive group （n = 750） and active group （n = 250）. The occurrence of renal， pulmonary， cutaneous， arthritis manifestations were significantly higher than those of the inactive group （all P < 0.05）. All patients were tested for ANCA， and the most common pattern being perinuclear or p-ANCA， the percentage of p-ANCA seropositive increased greatly with the increased disease activity （P < 0.05）. The autoantibodies were further analyzed between the two groups， 25 patients had reactivity to MPO， but no patient had reactivity to PR3. Also， there were significant differences in anti-dsDNA antibody， anti-nucleosome antibody between the two groups （P < 0.05）. In the active group， patients with p-ANCA seropositive exhibited higher serum beta-2-microglobulin （β2-MG）， titers of anti-dsDNA antibody， SLEDAI scores， lower albumin， C3， and C4 levels （P < 0.05）. Meanwhile， p-ANCA was associated with IL-6， which increased significantly with the increase of SLEDAI score. In addition， patients with p-ANCA seropositive had more occurrence of lupus nephritis， but it had no association with the renal pathology. Conclusion The appearance of p-ANCA in SLE patients indicated more severe disease activity status.
| 1 | KITCHING A R， ANDERS H J， BASU N， et al. ANCA-associated vasculitis［J］. Nat Rev Dis Primers， 2020， 6（1）：71. doi:10.1038/s41572-020-0204-y |
| 2 | ROSS C， MAKHZOUM J P， PAGNOUX C. Updates in ANCA-associated vasculitis［J］. Eur J Rheumatol， 2022，9（3）：153-166. doi:10.5152/eujrheum.2022.20248 |
| 3 | DOMINGUEZ-QUINTANA M， ALBA M A， HINOJOSA-AZAOLA A. Classification of ANCA-associated vasculitis： differences basedon ANCA specificity and clinicopathologic phenotype［J］. Rheumatol Int， 2021， 41（10）：1717-1728. doi:10.1007/s00296-021-04966-5 |
| 4 | WANG J， GUO H X， CHENG T， et al. Reduced circulating Tregs and positive pANCA were robustly associated with the occurrence of antiphospholipid syndrome in patients with systemic lupus erythematosus［J］. Lupus， 2023， 32（6）：746-755. doi:10.1177/09612033231171287 |
| 5 | PAN Y， HE L. Perinuclear anti-neutrophil cytoplasmic antibody in systemic lupus erythematosus indicates more severe condition［J］. Clin Biochem， 2021，89：38-43. doi:10.1016/j.clinbiochem.2020.12.004 |
| 6 | 闫吉，曹咏. ANCA与其不典型靶抗原在SLE患者血清检测中的临床意义［J］. 中国实验诊断学，2020，24（8）：1284-1285. doi:10.3969/j.issn.1007-4287.2020.08.017 |
| 7 | SANTOS J E， VICENTE R， MALVAR B， et al.Lupus-like nephritis with positive anti-neutrophil cytoplasmic antibodies and negative antinuclear antibodies［J］. J Bras Nefrol， 2022， 44（1）：121-125. doi:10.1590/2175-8239-jbn-2020-0114 |
| 8 | ARINGER M， COSTENBADER K， DAIKH D， et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus［J］. Ann Rheum Dis， 2019， 78（9）：1151-1159. |
| 9 | WANG S， SHANG J， XIAO J， et al. Clinicopathologic characteristics and outcomes of lupus nephritis with positive antineutrophil cytoplasmic antibody［J］. Ren Fail， 2020，42（1）：244-254. doi:10.1080/0886022x.2020.1735416 |
| 10 | MOISEEV S， COHEN TERVAERT J W， ARIMURA Y， et al. 2020 international consensus on ANCA testing beyond systemic vasculitis［J］. Autoimmun Rev， 2020， 19（9）：102618. doi:10.1016/j.autrev.2020.102618 |
| 11 | PANG Y， RUAN H， WU D， et al. Assessment of clinical activity and severity using serum ANCA and ASCA antibodies in patients with ulcerative colitis［J］. Allergy Asthma ClinImmunol， 2020， 16：37. doi:10.1186/s13223-020-00433-1 |
| 12 | LOU H， LING G S， CAO X. Autoantibodies in systemic lupus erythematosus： From immunopathology to therapeutic target［J］. J Autoimmun， 2022， 132：102861. doi:10.1016/j.jaut.2022.102861 |
| 13 | WEINER M， SEGELMARK M. The clinical presentation and therapy of diseases related to anti-neutrophil cytoplasmic antibodies （ANCA） ［J］. Autoimmun Rev， 2016， 15（10）： 978-982. doi:10.1016/j.autrev.2016.07.016 |
| 14 | LACETERA R， CALATRONI M， ROGGERO L， et al.Prevalence and clinical significance of ANCA positivity in lupus nephritis： a case series of 116 patients and literature review［J］. J Nephrol， 2023，36（4）：1059-1070. doi:10.1007/s40620-023-01574-3 |
| 15 | GAU C C， TSENG M H， WU C Y， et al. The Impact of Serum Anti-neutrophil Cytoplasmic Antibody on Clinical Characteristics and Outcomes in Pediatric-Onset Systemic Lupus Erythematosus Patients［J］. Front Med （Lausanne）， 2021， 8：647510. doi:10.3389/fmed.2021.647510 |
| 16 | TRIVIOLI G， MARQUEZ A， MARTORANA D， et al. Genetics of ANCA-associated vasculitis： role in pathogenesis， classification and management［J］. Nat Rev Rheumatol， 2022， 18（10）：559-574. doi:10.1038/s41584-022-00819-y |
| 17 | 胡静，黄卓春，王丽，等. ANCA及其特异性抗体在SLE患者中的应用价值初探［J］. 国际检验医学杂志，2021， 42（11）：1281-1290. doi:10.3969/j.issn.1673-4130.2021.11.001 |
| 18 | VOJDANI A， VOJDANI E， HERBERT M， et al. Correlation between Antibodies to Bacterial Lipopolysaccharides and Barrier Proteins in Sera Positive for ASCA and ANCA［J］. Int J Mol Sci， 2020，21（4）：1381. doi:10.3390/ijms21041381 |
| 19 | SHEN P， HAN L， CHEN G， et al. Emodin Attenuates Acetaminophen-Induced Hepatotoxicity via the cGAS-STING Pathway［J］. Inflammation， 2022， 45（1）：74-87. doi:10.1007/s10753-021-01529-5 |
| 20 | WEINSTEIN A， ALEXANDER R V， ZACK D J. A Review of Complement Activation in SLE［J］. Curr Rheumatol Rep， 2021， 23（3）：16. doi:10.1007/s11926-021-00984-1 |
| 21 | YOU T， LIN X， ZHANG C， et al. Correlation between serum β2-microglobulin level and systemic lupus erythematosus disease activity：A PRISMA-compliant meta-analysis［J］. Medicine （Baltimore）， 2022， 101（39）：e30594. doi:10.1097/md.0000000000030594 |
| 22 | LIU L， WANG R， DING H， et al. The utility of urinary biomarker panel in predicting renal pathology and treatment response in Chinese lupus nephritis patients［J］. PLoS One， 2020， 15（10）：e0240942. doi:10.1371/journal.pone.0240942 |
| 23 | SAID D， RASHAD N M， ABDELRAHMANC N S， et al. Antineutrophil cytoplasmic antibody in lupus nephritis： correlation with clinicopathological characteristics and disease activity［J］. Curr Rheumatol Rev， 2021，17（2）：213-221. doi:10.2174/1573397116999201208213422 |
| 24 | 凌磊，皮肖冰，余旸弢，等. 系统性红斑狼疮患者血清干扰素-α的水平变化及其临床意义［J］. 实用医学杂志， 2016， 32（1）：106-108. doi:10.3969/j.issn.1006-5725.2016.01.033 |
| 25 | ARINGER M. Inflammatory markers in systemic lupus erythematosus［J］. J Autoimmun， 2020， 110： 102374. doi:10.1016/j.jaut.2019.102374 |
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