抗唾液腺蛋白1抗体联合抗腮腺分泌蛋白抗体对干燥综合征的诊断价值

doi:10.19723/j.issn.1671-167X.2024.05.015

摘要/Abstract

摘要：

目的: 探讨抗唾液腺蛋白1(salivary protein 1, SP1)抗体联合抗腮腺分泌蛋白(parotid secretory protein, PSP)抗体在干燥综合征(Sjögren’s syndrome，SS)诊断中的价值。方法: 收集2020年1月至2022年12月就诊于河北医科大学第二医院风湿免疫科门诊及住院部的原发性SS(primary SS, pSS)患者60例, 其他自身免疫病伴有口干和(或)眼干症状的患者30例为疾病对照组，体检中心的健康体检者30例为健康对照组，留取血清备用，同时记录一般资料、临床表现、实验室指标及其它辅助检查。采用2016年美国风湿病学会(American College of Rheumatology，ACR)/欧洲抗风湿病联盟(European League against Rheumatism，EULAR)干燥综合征分类标准作为pSS诊断金标准。采用化学发光免疫分析法检测免疫球蛋白G(immunoglobulin G，IgG)型抗SP1抗体和抗PSP抗体。用受试者工作特征(receiver operating characteristic, ROC)曲线评估抗SP1抗体和抗PSP抗体诊断pSS的准确性，并比较pSS组中抗SP1抗体和抗PSP抗体阳性患者与阴性患者的临床特征。采用t检验及Mann-Whitney U检验、方差分析、Kruskal-Wallis检验、卡方检验或Fisher确切概率法、Spearman相关分析进行统计学分析。结果: 3组之间年龄(F=1.406，P=0.495)、性别(χ²=2.105，P=0.349)差异无统计学意义。抗SP1抗体(H=16.73, P < 0.001)和抗PSP抗体(H=26.09, P < 0.001)在3组之间表达水平差异有统计学意义。组间比较发现，抗SP1抗体和抗PSP抗体表达水平在pSS和健康对照组之间差异均有统计学意义(P < 0.001)，抗PSP抗体表达水平在疾病对照组和健康对照组之间差异有统计学意义(P=0.009)。在pSS组、疾病对照组、健康对照组中，抗SP1抗体阳性率分别为58.33% vs. 40.00% vs.13.33%，差异有统计学意义(P < 0.001)；抗PSP抗体阳性率分别为75.00% vs. 56.17% vs.16.67%，差异有统计学意义(P < 0.001)。抗SP1抗体、抗PSP抗体的曲线下面积分别为0.688(P < 0.001)、0.720 (P < 0.001)，敏感性分别为58.33%(35/60)和75.00%(45/60)，特异性分别为70.00%(42/60)和63.33%(38/60)，阳性预测值分别为66.04%(35/53)和67.16%(45/67)，阴性预测值分别为54.55%(42/77)和71.70%(38/53)。13例pSS患者中抗干燥综合征A (Sjögren’s syndrome A, SSA, 包括SSA52和SSA60)抗体和抗干燥综合征B (Sjögren’s syndrome B, SSB) 抗体均阴性，其中11例抗SP1抗体和抗PSP抗体均阳性，1例抗SP1抗体单独阳性，1例抗PSP抗体单独阳性。在pSS患者中，分别对抗SP1抗体和抗PSP抗体阳性与阴性组临床特征进行比较，抗SP1抗体阳性较阴性患者病程短(Z=-2.277，P=0.023)；抗PSP抗体阳性较阴性患者比较：年龄相对较轻(t=2.598，P < 0.05)，类风湿因子(rheumatoid factor，RF)阳性率较高(P=0.002)，IgG水平相对较高(t=3.806，P=0.003)；对pSS患者抗SP1抗体和抗PSP抗体的相关性进行分析，发现二者之间存在明显的相关性(r=0.801，P < 0.001)。结论: 抗SP1抗体和抗PSP抗体在SS诊断中价值均较高，其中抗SP1抗体有助于pSS的早期诊断；两种抗体联合检测有助于抗SSA抗体和抗SSB抗体阴性pSS患者的早期诊断。

关键词: 干燥综合征, 抗唾液腺蛋白抗体, 抗腮腺分泌蛋白抗体

Abstract:

Objective: To assess the diagnostic value of anti-salivary gland protein-1 (SP1) antibody combined with anti-parotid secretory protein (PSP) antibody for Sjögren's syndrome (SS). Methods: A total of 60 patients with primary SS (pSS) who were treated in the outpatient and inpatient department of Department of Rheumatology and Immunology of the Second Hospital of Hebei Medical University from January 2020 to December 2022 were collected. Thirty patients with other autoimmune diseases accompanied by dry mouth and/or dry eyes were collected as disease control group. Thirty healthy subjects from the physical examination center were collected for healthy control group, serum samples were obtained from all of them. Their general features and clinical information including clinical manifestations, laboratory examinations and other examinations were recorded. The 2016 American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) classification criteria were adopted as the diagnostic standard of pSS. Immunoglobulin G (IgG) subtype of anti-SP1 antibody and anti-PSP antibody were detected by chemiluminescence immunoassay. The receiver operating characteristic (ROC) curve was used to evaluate the accuracy of anti-SP1 antibody and anti-PSP antibody in diagnosing pSS.The cli-nical characteristics of anti-SP1 antibody and anti-PSP antibody positive patients and negative patients in pSS group were further compared. Independent samples t test, Mann-Whitney U test, variance analysis, Kruskal-Wallis test, Chi-square test or Fisher's exact test and Spearman correlation analysis were used for statistical analysis. Results: There was no significant difference in age (F=1.406, P=0.495) and gender (χ²=2.105, P=0.349) among pSS group, disease control group and healthy control group. The expression levels of anti-SP1 antibody (H=16.73, P < 0.001) and anti-PSP antibody (H=26.09, P < 0.001) were statistically different among the three groups. An intergroup comparison of anti-SP1 antibody expression levels showed that there was a statistically significant difference between pSS and healthy control group (P < 0.001), but no statistically significant difference between the other groups. Comparison of anti-PSP antibody expression levels between the groups showed that there were statistically significant differences between pSS and healthy control group (P < 0.001), and between disease control group and healthy control group (P=0.009), while no statistically significant differences between the other groups. The positive rate of anti-SP1 antibody in pSS group was significantly higher than that in disease control group and healthy control group (58.33% vs. 40.00% vs. 13.33%, P < 0.001). The positive rate of anti-PSP antibody in pSS group was significantly higher than that in disease control group and healthy control group (75.00% vs. 56.17% vs. 16.67%, P < 0.001). The area under the curve for anti-SP1 antibody was 0.688 (P < 0.001). The sensitivity and specificity of anti-SP1 antibody were 58.33% (35/60) and 70.00% (42/60) respectively, the positive predictive value was 66.04% (35/53) and the negative predictive value was 54.55% (42/77) of anti-SP1 antibody.The area under the curve of anti-PSP antibody was 0.720 (P < 0.001), with a sensitivity was 75.00% (45/60), and specificity was 63.33% (38/60).The positive predictive value and negative predictive value of anti-PSP antibody were 67.16% (45/67) and 71.70% (38/53) respectively. All the 13 pSS patients were negative for anti-Sjögren's syndrome A (SSA, including SSA52 and SSA60) antibody and anti- Sjögren's syndrome B (SSB) antibody. Among them, 11 patients were positive for both anti-SP1 antibody and anti-PSP antibody, 1 patient was positive for anti-SP1 antibody and 1 patient was positive for anti-PSP antibody. The clinical features of anti-SP1 antibody and anti-PSP antibody positive and negative groups were compared in pSS patients. The duration of disease in anti-SP1 antibody positive group was shorter (Z=-2.277, P=0.023) when compared with the negative patients. The patients with positive anti-PSP antibody were younger than those in the negative group (t=2.598, P < 0.05), the positive rate of rheumatoid factor (P=0.002) and the serum level of IgG (t=3.806, P=0.003) in anti-PSP antibody positive group were higher than in the negative group. Analysis of the correlation between anti-SP1 antibody and anti-PSP antibody in the pSS patients showed that there was significant correlation between them (r=0.801, P < 0.001). Conclusion: Both anti-SP1 antibody and anti-PSP antibody are valuable in the diagnosis of SS, and anti-SP1 antibody is helpful for the early diagnosis of pSS. The combined detection of anti-SP1 antibody and anti-PSP antibody is helpful for the early diagnosis of pSS patients with negative anti-SSA antibody and anti-SSB antibody.

Key words: Sjögren's syndrome, Anti-salivary gland protein 1 antibody, Anti-parotid secretory protein antibody

中图分类号:

R593.2

杨玉淑, 齐晅, 丁萌, 王炜, 郭惠芳, 高丽霞. 抗唾液腺蛋白1抗体联合抗腮腺分泌蛋白抗体对干燥综合征的诊断价值[J]. 北京大学学报（医学版）, 2024, 56(5): 845-852.

Yushu YANG, Xuan QI, Meng DING, Wei WANG, Huifang GUO, Lixia GAO. Diagnostic values of anti-salivary gland protein-1 antibody combined with anti-parotid secretory protein antibody for Sjögren's syndrome[J]. Journal of Peking University (Health Sciences), 2024, 56(5): 845-852.

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Items	pSS	Disease control	Healthy control	H	P
Anti-SP1 antibody/ (U/mL)，M (P₂₅, P₇₅)	8.93 (5.43, 17.04)	6.21 (4.01, 11.97)	5.08 (3.05, 6.85)	16.73	0.002
Anti-PSP antibody/(U/mL), M (P₂₅, P₇₅)	7.02 (4.58, 13.34)	4.86 (3.45, 8.88)	2.67 (2.29, 4.24)	26.09	< 0.001

Items	Anti-SP1antibody(+) (n=35)	Anti-SP1antibody(-) (n=25)	t/Z/χ²	P
Age/years,$\bar{x} \pm s$	49.3±13.3	52.5±13.3	0.903	0.371
Female, n (%)	34 (97.1)	24 (96.0)		＞0.999^a
Duration/months, M (P₂₅, P₇₅)	21 (10, 36)	36 (15, 60)	-2.277	0.023
WBC/(×10⁹/L),$\bar{x} \pm s$	5.2±1.6	4.3±1.7	1.489	0.142
PLT/(×10⁹/L),$\bar{x} \pm s$	181.1±71.2	180.5±91.0	0.027	0.979
IgG/(g/L),$\bar{x} \pm s$	19.1±8.9	20.7±7.2	1.519	0.303
RF/(U/mL), n (%)	13 (52.0)	15 (42.9)	0.490	0.488
ANA, n (%)	23 (92.0)	33 (94.3)		＞0.999^a
Anti-SSA52, n (%)	20 (80.0)	23 (65.7)	1.466	0.226
Anti-SSA60, n (%)	16 (64.0)	19 (54.3)	0.566	0.452
Anti-SSB, n (%)	7 (28.0)	7 (25.0)	0.522	0.470
ACA, n (%)	3 (12.0)	3 (8.6)		0.686^a
Biopsy, n (%)	19 (76.0)	27 (77.1)	2.307	0.511
Oral dryness, n (%)	30 (85.7)	23 (92.0)		0.688^a
Ocular dryness, n (%)	20 (57.1)	15 (60.0)		＞0.999^a
ILD, n (%)	13 (37.1)	10 (40.0)		＞0.999^a
Enlargemen of salivary glands, n (%)	7 (20.0)	1 (4.0)		0.123^a
Rash, n (%)	7 (28.0)	7 (25.0)	0.522	0.470
ITP, n (%)	6 (17.1)	4 (16.0)		＞0.999^a

Items	Anti-PSP antibody(+) (n=45)	Anti-PSP antibody(-) (n=15)	t/Z/ χ²	P
Age/years,$\bar{x} \pm s$	48.2±13.7	58.0±8.8	2.598	0.012
Female, n (%)	43 (95.6)	15 (100)		＞0.999^a
Duration/months, M (P₂₅, P₇₅)	24 (12, 48)	30 (12, 57)	-1.414	0.157
WBC/(×10⁹/L),$\bar{x} \pm s$	4.9±2.4	4.8±1.9	0.097	0.923
PLT/(×10⁹/L),$\bar{x} \pm s$	179.2±87.7	185.6±67.7	0.252	0.802
IgG/(g/L),$\bar{x} \pm s$	21.8±7.9	13.5±2.6	3.086	0.003
RF/(U/mL), n (%)	27 (60.0)	2 (1.3)		0.002^a
ANA, n (%)	42 (93.3)	14 (93.3)		＞0.999^a
Anti-SSA52, n (%)	33 (73.3)	10 (66.7)	0.246	0.620
Anti-SSA60, n (%)	27 (60.0)	8 (53.3)	0.208	0.650
Anti-SSB, n (%)	15 (33.3)	3 (20.0)		0.517^a
ACA, n (%)	3 (6.7)	3 (20.0)		0.159^a
Biopsy, n (%)	33 (73.3)	13 (86.7)	2.115	0.159
Oral dryness, n (%)	39 (86.7)	14 (6.9)		0.668^a
Ocular dryness, n (%)	26 (57.8)	9 (60.0)		＞0.999^a
ILD, n (%)	17 (37.8)	6 (40.0)		＞0.999^a
Enlargemen of salivary glands, n (%)	7 (15.6)	1 (6.7)		0.656^a
Rash, n (%)	10 (22.2)	4 (26.7)		0.734^a
ITP, n (%)	8 (17.8)	2 (13.3)		＞0.999^a

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