干燥综合征患者血清PI3K和Akt水平与血小板减少的关系及其临床意义

摘要/Abstract

摘要：

目的探讨干燥综合征（SS）患者血清中磷脂酰肌醇3-激酶（PI3K）和蛋白激酶B（Akt）水平变化，并阐明其与SS患者血小板减少（TP）的关系。方法选取2022年1月-2024年12月本院收治的SS患者198例，根据血小板（PLT）计数水平分为SS-TP组（n=51）和SS-non-TP（NTP）组（n=147）。收集2组患者的临床资料，采用Pearson相关分析法分析SS患者血清中PI3K和Akt水平与PLT计数的相关性，χ²检验和独立样本t检验分析SS患者临床资料与TP的关系，多因素Logistic回归分析筛选SS患者并发TP的独立预测因子，并绘制受试者工作特征（ROC）曲线以评价预测因子的预测效能，采用决策曲线评估预测因子的临床实用性。结果 198例SS患者中，并发TP的患者51例（25.76%）作为SS-TP组，其余患者作为SS-NTP组。与SS-NTP组比较，SS-TP组患者血清中PI3K和Akt水平明显降低（P<0.001）。SS患者血清中PI3K（r=0.416，P<0.001）和Akt（r=0.425，P<0.001）水平与PLT计数呈正相关关系。与SS-NTP组比较，SS-TP组患者淋巴结肿大百分率明显升高（P<0.05），淋巴细胞计数和血红蛋白水平明显降低（P<0.05）。Logistic回归模型，SS患者并发TP与淋巴细胞计数、血红蛋白水平和血清中PI3K水平及Akt水平降低有关联（P<0.001）。血清中PI3K水平预测SS患者并发TP的曲线下面积（AUC）值为0.770，血清中Akt水平预测SS患者并发TP的AUC值为0.763，二者联合预测的AUC值为0.853。血清中PI3K水平和血清中Akt水平联合预测SS患者并发TP的效能优于二者各自单独预测（联合预测-血清PI3K水平：Z=2.779，P=0.006；联合预测-血清Akt水平：Z=2.907，P=0.004）。在阈值为0.10~0.82时，血清中PI3K和Akt水平联合预测SS患者并发TP风险的净受益率高于血清PI3K及Akt水平单独评估。结论血清中PI3K和Akt水平降低与SS患者并发TP风险有关联，且二者联合评估对TP发生具有较高的预测价值。

关键词: 干燥综合征, 磷脂酰肌醇3-激酶, 蛋白激酶B, 血小板减少, 淋巴细胞, 血红蛋白

Abstract:

Objective To discuss the changes of the levels of phosphatidylinositol 3-kinase （PI3K） and protein kinase B （Akt） in serum of the patients with Sj?gren’s syndrome （SS）， and to clarify their relationships with thrombocytopenia （TP） in the SS patients. Methods A total of 198 SS patients admitted to our hospital from January 2022 to December 2024 were selected. According to the platelet （PLT） count levels， they were divided into SS-TP group （n=51） and SS-non-TP （NTP） group （n=147）. The clinical data of the patients in two groups were collected； Pearson correlation analysis was used to analyze the correlations between the serum levels of PI3K and Akt and PLT count in the SS patients； χ2 test and independent sample t test were used to analyze the relationships between the clinical data of the SS patients and TP； multivariate Logistic regression analysis was used to screen the independent predictors for the risk of TP in the SS patients； receiver operating characteristic （ROC） curve was drawn to evaluate the predictive efficacy of the predictors； decision curve was used to assess the clinical utility of the predictors. Results Among the 198 SS patients， 51 patients （25.76%） complicated with TP were included as SS-TP group， and the remaining patients were included as SS-NTP group. Compared with SS-NTP group， the serum levels of PI3K and Akt of the patients in SS-TP group were significantly decreased （P<0.05）. The serum levels of PI3K （r=0.416， P<0.001） and Akt （r=0.425， P<0.001） of the SS patients were positively correlated with PLT count. Compared with SS-NTP group， the percentage of lymphadenectasis of the patients in SS-TP group was significantly increased （P<0.05）， and the lymphocyte count and hemoglobin level were significantly decreased （P<0.05）. The Logistic regression analysis results showed that the concurrent TP in the SS patients was associated with the decrease in the lymphocyte count， hemoglobin level， and serum levels of PI3K and Akt （P<0.05 or P<0.01）. The area under curve （AUC） value of serum PI3K level for predicting concurrent TP in the SS patients was 0.770， the AUC value of serum Akt level for predicting concurrent TP in the SS patients was 0.763， and the AUC value of the combined prediction of the two was 0.853. The efficacy of the combined prediction of serum PI3K level and serum Akt level for concurrent TP in the SS patients was better than that of either alone （combined prediction-serum PI3K level： Z=2.779， P=0.006； combined prediction-serum Akt level： Z=2.907， P=0.004）. Within the threshold range of 0.10-0.82， the net benefit rate of the combined prediction of serum PI3K and Akt levels for the risk of concurrent TP in the SS patients was higher than that of the separate assessment of serum PI3K or Akt level. Conclusion The decreasing of serum PI3K and Akt levels are associated with the risk of concurrent TP in SS patients， and the combined assessment of the two has a high predictive value for the occurrence of TP.

Key words: Sj?gren’s syndrome, Phosphatidylinositol 3-kinase, Protein kinase B, Thrombocytopenia, Lymphocyte, Hemoglobin

中图分类号:

R593.2

刘晓,费飞,刘涛,秦兰. 干燥综合征患者血清PI3K和Akt水平与血小板减少的关系及其临床意义[J]. 吉林大学学报(医学版), 2026, (): 1-8.

Xiao LIU,Fei FEI,Tao LIU,Lan QIN. Relationship between serum PI3K and Akt levels and thrombocytopenia in patients with Sjögren’s syndrome and its clinical significance[J]. Journal of Jilin University(Medicine Edition), 2026, (): 1-8.

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Characteristic	SS-NTP (n=147)	SS-TP (n=51)	χ²/t	P
Gender （%）			0.006	0.939
Male	13(8.84)	5(9.80)
Female	134(91.16)	46(90.20)
Age （year)	48.89±4.07	49.26±4.14	0.557	0.578
BMI （kg·m^-2）	23.12±2.44	22.86±2.38	0.660	0.510
Duration of disease （month）	40.31±10.02	38.95±9.69	0.842	0.401
Family history of rheumatic diseases （%）	22(14.97)	8(15.69)	0.015	0.902
SS activity index	9.44±1.95	10.06±2.01	1.941	0.054
Clinical manifestations （%）
Dry eyes	60(40.82)	21(41.18)	0.002	0.964
Dry mouth	90(61.22)	33(64.71)	0.195	0.659
Parotid gland enlargement	92(62.59)	31(60.78)	0.052	0.819
Fatigue	48(32.65)	17(33.33)	0.008	0.929
Arthralgia	79(53.74)	25(49.02)	0.339	0.561
“Rampant” caries	21(14.29)	8(15.69)	0.059	0.807
Raynaud’s phenomenon	12(8.16)	5(9.80)	0.005	0.944
Peripheral neuropathy	28(19.05)	10(19.61)	0.008	0.930
Dysphagia	12(8.16)	4(7.84)	0.051	0.821
Lymphadenopathy	14(9.52)	12(23.53)	6.511	0.011
Blood routine indicators
White blood cell count （×10⁹ L^-1)	4.07±0.41	3.97±0.36	1.547	0.124
Neutrophil count （×10⁹ L^-1)	2.50±0.46	2.45±0.42	0.684	0.495
Lymphocyte count （×10⁹ L^-1)	1.40±0.32	1.12±0.29	5.511	<0.001
Hemoglobin （g·L^-1)	128.81±22.04	109.65±24.49	5.196	<0.001
Immune-related indicator
Complement C3 （g·L^-1）	0.86±0.07	0.84±0.06	1.821	0.070
Complement C4 （g·L^-1）	0.22±0.04	0.21±0.03	1.632	0.104
IgM （g·L^-1）	1.17±0.23	1.20±0.25	0.785	0.434
IgA （g·L^-1）	2.61±0.79	2.78±0.81	1.316	0.190
IgG （g·L^-1）	13.97±3.92	14.28±3.86	0.489	0.626
CD4⁺/CD8⁺ lymphocyte ratio	1.71±0.38	1.62±0.35	1.486	0.139
Percentage of NK cell （%）	11.20±2.51	10.59±2.35	1.520	0.130
ANA （+）（%）	125(85.03)	41(80.39)	0.602	0.438
Anti-SSA （+）（%）	80(54.42)	27(52.94)	0.033	0.855
Anti-SSB （+）（%）	30(20.41)	11(21.57)	0.031	0.860
RF （+）（%）	33(22.45)	10(19.61)	0.180	0.672

Variable	Type	Assignment
Dependent variable
Incidence of TP	Dichotomous variable	No=0, Yes=1
Independent variables
Lymphadenopathy	Dichotomous variable	No=0, Yes=1
Lymphocyte count	Continuous variable	Specific value
Hemoglobin level	Continuous variable	Specific value
PI3K level	Continuous variable	Specific value
Akt level	Continuous variable	Specific value

Variable	β	SE	Wald χ²	P	OR	95%CI
Lymphadenopathy	1.037	0.699	2.200	0.138	2.820	0.717-11.099
Lymphocyte count	－3.938	0.867	20.609	<0.001	0.019	0.004-0.107
Hemoglobin level	－0.479	0.120	16.082	<0.001	0.619	0.490-0.783
PI3K level	－0.519	0.125	17.195	<0.001	0.595	0.466-0.761
Akt level	－0.618	0.141	19.101	<0.001	0.539	0.408-0.711

Variable	AUC	95%CI	Z	P	Cut-off [ρ_B/(pg·L^-1)]	Youden index	Sensitivity (η/%)	Specificity (η/%)
PI3K	0.770	0.705—0.827	7.129	<0.001	≤6.83	0.468	70.59	76.19
Akt	0.763	0.698—0.821	6.813	<0.001	≤8.52	0.449	82.35	62.59
Combined	0.853	0.796—0.899	12.195	<0.001		0.573	80.39	76.87