抗SSB抗体阳性和阴性的原发性干燥综合征患者临床及免疫学特征的比较

doi:10.19723/j.issn.1671-167X.2023.06.007

摘要/Abstract

摘要：

目的: 分析抗干燥综合征抗原B (Sjögren ’ s syndrome type B, SSB)抗体阳性的原发性干燥综合征(primary Sjögren ’ s syndrome，pSS)患者与抗SSB抗体阴性的pSS患者之间临床表现及实验室指标的差异。方法: 回顾性收集2009—2019年于北京大学第三医院风湿免疫科住院的pSS患者的病历资料，采用t检验、Mann-Whitney秩和检验、卡方检验和Fisher确切概率法对抗SSB抗体阳性和抗SSB抗体阴性的pSS患者组的临床特征及实验室指标进行分析。结果: 共纳入pSS患者142例，其中女性137例，男性5例，平均年龄(54.8±13.3)岁，其中抗SSB抗体阳性患者44例(31.0%)。临床特征方面，抗SSB抗体阳性的pSS患者较抗体阴性患者的就诊年龄和起病年龄更小[就诊年龄：(50.9±14.5)岁vs. (56.5±12.4)岁，P < 0.05；起病年龄：(42.2±14.8)岁vs. (49.5±15.3)岁，P < 0.05]，出现皮疹(29.5% vs. 14.3%，P < 0.05)、腮腺肿大(27.3% vs. 8.2%，P < 0.05)、肾小管酸中毒(15.9% vs. 4.2%，P < 0.05)、免疫性血小板减少(9.1% vs. 1.0%，P < 0.05)的比例更高；两组患者在口干、眼干、雷诺现象(Raynaud phenomenon)等方面差异无统计学意义。实验室指标方面，抗SSB抗体阳性组患者与阴性组患者相比，类风湿因子(rheumatoid factor, RF)阳性率(85.0% vs. 49.4%, P < 0.05)及滴度(中位数89.8 IU/mL vs. 20.5 IU/mL，P < 0.05)、抗核抗体(antinuclear antibody，ANA)滴度(中位数320 vs. 160，P < 0.05)、抗干燥综合征抗原A (Sjögren ’ s syndrome type A, SSA)抗体阳性率(97.7% vs. 64.3%, P < 0.05)、IgG水平(中位数21.0 g/L vs. 15.6 g/L，P < 0.05)、γ球蛋白升高率(71.4% vs. 38.5%，P < 0.05)、CD3^-CD19⁺细胞比例[(21.0±11.9)% vs. (13.7±9.6)%，P < 0.05]均更高，而CD3⁺细胞比例[(67.2±14.4)% vs. (76.6±13.1)%，P < 0.05]和抗线粒体抗体M2亚型阳性率(10.5% vs. 35.6%，P < 0.05)相对更低，其余无明显差异。治疗方面，与抗SSB抗体阴性组患者相比，抗SSB抗体阳性组患者应用激素(90.9% vs. 73.5%，P < 0.05)及免疫抑制剂(54.5% vs. 36.7%，P < 0.05)的比例更高。结论: 与抗SSB抗体阴性pSS患者相比，抗SSB抗体阳性患者的起病年龄更小，临床表现更多样，血清其他自身抗体阳性率/水平及B细胞活化程度更高，治疗上需要应用激素及免疫抑制剂的概率更大，整体倾向于表现出更重的临床表型。

关键词: 原发性干燥综合征, 抗SSB抗体, 免疫学特征

Abstract:

Objective: To analyze the differences of clinical manifestations and laboratory features between primary Sjögren’s syndrome (pSS) patients with positive and negative anti-Sjögren’s syndrome type B (SSB) antibody. Methods: The clinical data of pSS patients hospitalized in Department of Rheumato-logy and Immunology, Peking University Third Hospital were retrospectively analyzed to investigate the differences of clinical and laboratory features between anti-SSB positive and negative groups. The t test, Mann-Whitney U test, Chi-square test and Fisher’s exact probability were used for analysis. Results: A total of 142 pSS patients were enrolled in this study, including 137 females and 5 males with a mean age of (54.8±13.3) years. The anti-SSB positive group included 44 patients accounting for 31.0% of the pSS patients. The anti-SSB positive pSS patients were younger at disease onset and at visit [age at visit: (50.9±14.5) years vs. (56.5±12.4) years; age at onset: (42.2±14.8) years vs. (49.5±15.3) years, P < 0.05]. The patients with anti-SSB positive more frequently presented with rash (29.5% vs. 14.3%, P < 0.05), enlargement of parotid glands (27.3% vs. 8.2%, P < 0.05), renal tubular acidosis (15.9% vs. 4.2%, P < 0.05), immune thrombocytopenia (9.1% vs. 1.0%, P < 0.05), rheumatoid factor (RF) positive (85.0% vs. 49.4%, P < 0.05), higher RF and antinuclear antibody (ANA) titers (median: 89.8 IU/mL vs. 20.5 IU/mL; median: 320 vs. 160, P < 0.05), anti-Sjögren’s syndrome type A (SSA) antibody positive (97.7% vs. 64.3%, P < 0.05), elevation of γ globulin (71.4% vs. 38.5%, P < 0.05), higher levels of IgG (median: 21.0 g/L vs. 15.6 g/L, P < 0.05), higher proportions of CD3^-CD19⁺ cells [(21.0±11.9)% vs. (13.7±9.6)%, P < 0.05] and lower proportions of CD3⁺ cells [(67.2±14.4)% vs. (76.6%±13.1)%, P < 0.05] than those negative. However, the anti-SSB positive group was less likely to show anti-mitochondrial antibodies (AMA)-M2 positivity (10.5% vs. 35.6%, P < 0.05). Glucocorticoids (90.9% vs. 73.5%, P < 0.05) and immunosuppressants (54.5% vs. 36.7%, P < 0.05) were more frequently used in anti-SSB positive pSS patients than those negative. Conclusion: The anti-SSB positive pSS patients were younger at disease onset while more frequently presenting with various symptoms, higher levels of other antibodies and activation of B cells than those negative. Glucocorticoids and immunosuppressants were more frequently used, indicating that anti-SSB positive group presented with a more severe clinal phenotype.

Key words: Primary Sjögren's syndrome, Anti-SSB antibody, Immunological characteristics

中图分类号:

R593.2

韩艺钧,李常虹,陈秀英,赵金霞. 抗SSB抗体阳性和阴性的原发性干燥综合征患者临床及免疫学特征的比较[J]. 北京大学学报（医学版）, 2023, 55(6): 1000-1006.

Yi-jun HAN,Chang-hong LI,Xiu-ying CHEN,Jin-xia ZHAO. Comparison of clinical and immunological characteristics between primary Sjögren's syndrome patients with positive and negative anti-SSB antibody[J]. Journal of Peking University (Health Sciences), 2023, 55(6): 1000-1006.

图/表 3

表1

表2

抗SSB抗体阳性与抗SSB抗体阴性pSS患者实验室检查指标的比较"

Items	Anti-SSB (+), n=44	Anti-SSB (-), n=98	t/Z	χ²	P
WBC/(×10⁹/L)	5.47±3.18	5.82±2.55	0.699		0.486
RBC/(×10¹²/L)	3.92±0.59	3.95±0.63	0.324		0.746
HB/(g/L)	117.86±16.99	119.40±18.06	0.477		0.634
PLT/(×10⁹/L)	185.25±95.79	191.27±88.85	0.364		0.716
N/%	59.03±13.57	59.93±14.31	0.353		0.725
L/%	30.93±11.70	59.93±14.31	-0.791		0.430
ALT/(U/L)	18.5 (12.0, 29.8)	17.0 (13.0, 33.0)	-0.795		0.427
AST/(U/L)	20.0 (17.0, 31.2)	23.0 (17.0, 34.0)	-1.022		0.307
GGT/(U/L)	21.0 (14.2, 35.0)	25.0 (15.0, 59.0)	-1.254		0.210
ALP/(U/L)	67.88±42.58	69.38±31.24	0.231		0.818
Alb/(g/L)	38.21±3.84	38.02±5.17	-0.212		0.833
TBil/(mmol/L)	11.34±5.94	12.83±8.95	0.990		0.324
TBA/(μmol/L)	5.15 (3.55, 7.58)	3.70 (2.00, 7.60)	1.170		0.242
Scr/(mmol/L)	73.70±23.39	68.74±26.70	-1.061		0.291
CRP/(mg/L)	0.27 (0.17, 0.54)	0.28 (0.17, 0.53)	-0.669		0.503
ESR/(mm/h)	34.50±25.43	26.59±20.96	-1.762		0.083
RF positivity	34/44 (85.0)	42/85 (49.4)		14.450	<0.05^*
RF titer/(IU/mL)	89.8 (31.2, 355.2)	20.5 (0, 84.3)	-4.507		<0.05^*
ANA positivity	44 (100.0)	91/96 (94.8)			0.325^#
ANA titer	320.0 (252.5, 640.0)	160.0 (80.0, 320.0)	-4.512		<0.05^*
Anti-SSA (+)	43 (97.7)	63 (64.3)		17.945	<0.05^*
Anti-Sm (+)	0 (0)	1/93 (1.1)			>0.999^#
Anti-U1RNP (+)	2/39 (5.1)	12/93 (12.9)			0.230^#
Anti-rRNP (+)	1/39 (2.6)	3/92 (3.3)			>0.999^#
AMA-M2 (+)	2/19 (10.5)	16/45 (35.6)		4.140	0.042^*
γG elevation	25/35 (71.4)	25/65 (38.5)		9.890	0.002^*
IgG/(g/L)	21.0 (16.0, 30.0)	15.6 (12.5, 19.6)	4.332		<0.05^*
IgA/(g/L)	3.60±1.36	3.14±1.39	-1.786		0.076
IgM/(g/L)	1.29±0.83	1.43±1.02	0.782		0.436
C3/(g/L)	0.93±0.24	0.93±0.24	0.057		0.955
C4/(g/L)	0.17 (0.15, 0.22)	0.18 (0.15, 0.21)	0.188		0.851
CD3⁺/%^a	67.2±14.4	76.6±13.1	2.033		0.048^*
CD3⁺CD4⁺/%^a	40.33±9.48	39.37±14.07	-0.211		0.833
CD3⁺CD8⁺/%^a	40.33±9.48	34.76±18.09	1.967		0.055
CD3^-CD19⁺/%^a	21.0±11.9	13.7±9.6	-2.095		0.042^*

表2

表3

参考文献 25

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Items	Anti-SSB (+), n=44, n (%)	Anti-SSB (-), n=98, n (%)	χ²	P
Oral dryness	41 (93.2)	88 (89.8)		0.754^#
Ocular dryness	30 (68.2)	65 (66.3)	0.047	>0.999
Raynaud phenomenon	5 (11.4)	11 (11.2)		>0.999^#
Rash	13 (29.5)	14 (14.3)	4.592	0.032^*
Enlargement of lymph nodes	15 (34.1)	28 (28.6)	0.438	0.508
Enlargement of parotid glands	12 (27.3)	8 (8.2)	9.164	0.002^*
Arthralgia	19 (43.2)	37 (37.8)	0.374	0.541
Rampant dental caries	23 (52.3)	42 (42.9)	1.085	0.298
Fever	12 (27.3)	24 (24.5)	0.124	0.724
Fatigue	20 (45.5)	30 (30.6)	2.932	0.087
Dyspnea	9 (20.5)	19 (19.4)	0.022	0.883
Hashimoto’s thyroiditis	2 (4.5)	5 (5.1)		>0.999^#
PBC	0 (0)	9 (9.2)		0.057^#
Autoimmune hepatitis	1 (2.3)	4 (4.1)		>0.999^#
RTA	7 (15.9)	4 (4.2)		0.035^#*
Hemolytic anemia	1 (2.3)	0 (0)		0.310^#
ITP	4 (9.1)	1 (1.0)		0.032^#*
Neurologic abnormalities	9 (20.5)	16 (16.3)	0.357	0.550
Dysfunction of esophagus	2 (4.5)	7 (7.1)		0.721^#
Atrophic gastritis	0 (0)	8 (8.2)		0.058^#
ILD	5 (11.4)	22 (22.4)	2.423	0.120
Pleural effusion	1 (2.3)	2 (2.0)		>0.999^#
PAH	3 (6.8)	7 (7.1)		>0.999^#
Positive lip biopsy	9/11 (81.8)	45/52 (86.5)		0.650^#

Items	Anti-SSB (+), n=44, n (%)	Anti-SSB (-), n=98, n (%)	χ²	P
Glucocorticoids	40 (90.9)	72 (73.5)	5.543	0.019^*
HCQ	35 (79.5)	71 (72.4)	0.808	0.369
TG	2 (4.5)	2 (2.0)		0.588^#
Immunosuppressants	24 (54.5)	36 (36.7)	3.948	0.047^*
CTX	8 (18.2)	15 (15.3)	0.185	0.667
MMF	9 (20.5)	10 (10.2)	2.753	0.097
CsA	2 (4.5)	5 (5.1)		>0.999^#
TAC	1 (2.3)	0 (0)		0.310^#
LEF	2 (4.5)	4 (4.5)		>0.999^#
MTX	1 (2.3)	2 (2.0)		>0.999^#
RTX	1 (2.3)	4 (4.1)		>0.999^#

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