系统性红斑狼疮合并视网膜病变的临床及免疫学特点

doi:10.19723/j.issn.1671-167X.2022.06.008

摘要/Abstract

摘要：

目的: 探讨系统性红斑狼疮(systemic lupus erythematosus, SLE)合并视网膜病变的临床及免疫学特点。方法: 选择2009年1月至2022年7月于北京大学人民医院住院的无高血压无糖尿病的SLE合并视网膜病变患者50例(眼病组)，按性别、年龄匹配病程中无视物模糊症状及眼底检查没有视网膜病变的SLE患者50例(非眼病组)，对两组患者的临床表现、实验室检查及淋巴细胞亚群进行分析。结果: 眼病组患者最常见的眼底表现为棉絮斑(33/50，66.0%)，其次是视网膜出血(31/50，62.0%)。视网膜病变可发生在SLE病程的任何阶段，中位时间为1年(病程范围为20 d至30年)。眼病组出现狼疮性肾炎比例(72.0% vs. 46.0%, P=0.008)和浆膜炎比例(58.0% vs. 28.0%, P=0.002)显著高于非眼病组。眼病组同时出现神经精神性狼疮(neuropsychiatric systemic lupus erythematosus, NPSLE)比例较非眼病组升高，但差异无统计学意义。与非眼病组相比，眼病组中抗心磷脂抗体阳性比例(30.0% vs. 12.0%, P=0.027)、系统性红斑狼疮疾病活动指数评分(中位数22.0 vs. 10.5, P < 0.001)、红细胞沉降率(P < 0.001)，C反应蛋白水平(P=0.019)和24 h尿蛋白定量(P=0.026)均显著升高，血红蛋白水平明显减低[(91.64±25.18) g/L vs. (113.96±18.57) g/L, P < 0.001]。与非眼病组相比，SLE视网膜病变患者外周血CD19⁺B细胞比例显著升高(P=0.010)，CD4⁺T细胞比例明显减低(P=0.025)，自然杀伤(natural killer，NK)细胞比例减低(P=0.051)。结论: SLE视网膜病变提示更高的SLE疾病活动性，更易合并肾脏系统、血液系统等损害，建议对所有SLE患者尽早进行眼底筛查。SLE视网膜病变患者可能存在更显著的B细胞异常增殖，应给予积极治疗以防止其他重要脏器受累。

关键词: 系统性红斑狼疮, 视网膜病变, 临床特点, 淋巴细胞亚群

Abstract:

Objective: To investigate the clinical and immunological characteristics of systemic lupus erythematosus (SLE) with retinopathy. Methods: Fifty SLE patients with retinopathy without hypertension and diabetes (retinopathy group) who were hospitalized in the Peking University People's Hospital from January 2009 to July 2022 were screened. Fifty SLE patients without blurred vision during the course of the SLE and without retinopathy in the fundus examinations (non-retinopathy group) matched for sex and age were selected. Their clinical manifestations, laboratory tests and lymphocyte subsets were statistically analyzed. Results: The most common fundus ocular change of the SLE patients with retinopathy was cotton-wool spots (33/50, 66.0%), followed by intraretinal hemorrhage (31/50, 62.0%). Retinopathy could occur at any stage of SLE duration, with a median of 1 year (20 days to 30 years). The proportion of lupus nephritis (72.0% vs. 46.0%, P=0.008) and serositis (58.0% vs. 28.0%, P=0.002) in the retinopathy group were significantly higher than those in the non-retinopathy group. The proportion of neuropsychiatric systemic lupus erythematosus (NPSLE) in the retinopathy group was higher, but there was no significant difference between the two groups. Compared with the non-retinopathy group, the proportion of positive anti-cardiolipin antibody (30.0% vs. 12.0%, P=0.027), the SLEDAI score (median 22.0 vs. 10.5, P < 0.001), erythrocyte sedimentation rate (P < 0.001), C-reactive protein (P=0.019) and twenty-four hours urine total protein level (P=0.026) in the retinopathy group were significantly higher, and the hemoglobin level was significantly lower [(91.64±25.18) g/L vs. (113.96±18.57) g/L, P < 0.001]. The proportion of CD19⁺ B cells in peripheral blood of the patients with SLE retinopathy was significantly increased (P=0.010), the proportion of CD4⁺ T cells was significantly decreased (P=0.025) and the proportion of natural killer (NK) cells was lower (P=0.051) when compared with the non-retinopathy group. Conclusion: Retinopathy in SLE suggests a higher activity of SLE disease with more frequent hematologic and retinal involvement. It is recommended to perform fundus examination as soon as a patient is diagnosed with SLE. SLE patients with retinopathy may have stronger abnormal proliferation of B cells, and aggressive treatment should be applied to prevent other important organs involvement.

Key words: Systemic lupus erythematosus, Retinopathy, Clinical characteristics, Lymphocyte subsets

中图分类号:

R593.24

李敏,侯林卿,金月波,何菁. 系统性红斑狼疮合并视网膜病变的临床及免疫学特点[J]. 北京大学学报（医学版）, 2022, 54(6): 1106-1111.

Min LI,Lin-qing HOU,Yue-bo JIN,Jing HE. Clinical and immunological characteristics of systemic lupus erythematosus with retinopathy[J]. Journal of Peking University (Health Sciences), 2022, 54(6): 1106-1111.

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参考文献 23

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Variable	Retinopathy group (n=50)	Non-retinopathy group (n=50)	χ²/U	P
SLEDAI, M (P₂₅, P₇₅)	22.00 (16.75, 29.00)	10.50 (6.0, 15.25)	223.5	< 0.001^#
Fever, n (%)	13 (26.0)	12 (24.0)	0.053	0.817
Rash, n (%)	16 (32.0)	17 (34.0)	0.045	0.832
Hair loss, n (%)	8 (16.0)	6 (12.0)	0.332	0.564
Mucosal ulcer, n (%)	7 (14.0)	6 (12.0)	0.088	0.766
Arthritis, n (%)	9 (18.0)	10 (20.0)	0.065	0.799
Vasculitis, n (%)	4 (8.0)	5 (10.0)	0.000	1.000^a
Myositis, n (%)	4 (8.0)	2 (4.0)	0.177	0.678^a
NPSLE, n (%)	10 (20.0)	4 (8.0)	2.076	0.148^a
Thrombocytopenia, n (%)	21 (42.0)	12 (24.0)	3.664	0.056
Leukopenia, n (%)	12 (24.0)	11 (22.0)	0.056	0.812
Cylindruria, n (%)	9 (18.0)	2 (4.0)	3.677	0.051^a
Hematuria, n (%)	25 (50.0)	12 (24.0)	7.250	0.007^*
Proteinuria, n (%)	30 (60.0)	20 (40.0)	4.000	0.046^*
Pyuria, n (%)	23 (46.0)	7 (14.0)	12.190	< 0.001^#
Lupus nephritis, n (%)	36 (72.0)	23 (46.0)	6.986	0.008^*
Serositis, n (%)	29 (58.0)	14 (28.0)	9.180	0.002^*

Variable	Retinopathy group (n=50)	Non-retinopathy group (n=50)	t/U	P
Hb/(g/L), ${\bar x}$±s	91.64±25.18	113.96±18.57	4.838	< 0.001^#
ESR/(mm/h), M (P₂₅, P₇₅)	42.00 (24.00, 64.50)	18.50 (7.00, 34.25)	583.5	< 0.001^#
CRP/(mg/L), M (P₂₅, P₇₅)	2.91 (1.61, 6.76)	1.41 (0.56, 6.89)	654.0	0.019^*
Alb/(g/L), ${\bar x}$±s	30.78±6.70	33.05±7.61	1.517	0.133
24 h-UTP/(g/d), M (P₂₅, P₇₅)	0.64 (0.22, 1.87)	0.19 (0.10, 1.44)	700.0	0.026^*
ANA (+), n (%)	46 (92.0)	45 (90.0)	0.000	1.000^a
Anti-dsDNA (+), n (%)	31 (62.0)	30 (60.0)	0.042	0.838
Anti-dsDNA/(IU/mL), M (P₂₅, P₇₅)	113.30 (29.80, 200.00)	49.60 (19.68, 200.00)	735.0	0.146
Anti-Sm antibody (+), n (%)	10 (20.0)	9 (18.0)	0.065	0.799
Anti-RNP antibody (+), n (%)	19 (38.0)	20 (40.0)	0.042	0.838
Anti-SSA antibody (+), n (%)	21 (42.0)	27 (54.0)	1.442	0.230
Anti-SSB antibody (+), n (%)	6 (12.0)	5 (10.0)	0.102	0.749
AnuA (+), n (%)	29(58.0)	24 (48.0)	1.004	0.316
AnuA/(RU/mL), M (P₂₅, P₇₅)	44.68 (8.23, 151.43)	22.63 (9.40, 186.42)	881.0	0.736
ACLA (+), n (%)	15 (30.0)	6 (12.0)	4.882	0.027^*
ACLA/(U/mL), M (P₂₅, P₇₅)	4.60 (2.00, 11.40)	3.50 (2.15, 7.28)	878.5	0.364
Anti-β₂ GP 1 (+), n (%)	15 (30.0)	10 (20.0)	1.477	0.224
Anti-β₂ GP 1/(RU/mL), M (P₂₅, P₇₅)	6.72 (2.08, 37.14)	7.47 (2.83, 14.61)	931.5	0.773
LAC (+), n (%)	9 (18.0)	3 (6.0)	2.367	0.121^a
LAC/s, M (P₂₅, P₇₅)	1.02 (0.95, 1.37)	0.99 (0.93, 1.13)	693.0	0.251
Coombs test (+), n (%)	29 (58.0)	20 (40.0)	7.241	0.072
IgA (g/L), ${\bar x}$±s	2.42±1.28	2.88±1.28	1.671	0.098
IgG/(g/L), M (P₂₅, P₇₅)	13.50 (10.25, 20.30)	13.90 (8.80, 19.00)	921.5	0.463
IgM/(g/L), M (P₂₅, P₇₅)	1.09 (0.56, 1.66)	0.90 (0.47, 1.36)	798.5	0.213
C3/(g/L), M (P₂₅, P₇₅)	0.41 (0.253, 0.627)	0.59 (0.385, 0.712)	704.5	0.006^*
C4/(g/L), M (P₂₅, P₇₅)	0.05 (0.025, 0.130)	0.12 (0.046, 0.157)	755.5	0.018^*

Variable	Retinopathy group	Non-retinopathy group	t/U	P
CD3⁺ T cells/%, ${\bar x}$±s	62.86±13.95	68.95±12.88	1.241	0.228
CD4⁺ T cells/%, ${\bar x}$±s	26.28±6.48	33.46±11.03	2.357	0.025^*
CD8⁺ T cells/%, ${\bar x}$±s	36.47±11.47	35.49±10.84	-0.244	0.809
CD19⁺ B cells/%, ${\bar x}$±s	28.50±15.37	16.49±9.89	-2.738	0.010^*
NK cells (%), M (P₂₅, P₇₅)	3.65 (1.53, 7.13)	5.10 (4.25, 7.25)	74.000	0.051