|
|
Predictive value of human circulating T immune index and platelet parameters on the therapeutic effect of systemic lupus erythematosus |
WANG Jing, YANG Xiaofei |
Department of Clinical Laboratory, The Second Affiliated Hospital of Air Force Military Medical University, Xi'an 710038 |
|
|
Abstract Objective To analyze the changes of CD4+CD28null T cells and platelet-bound complement cleavage products (PC4d) in patients with active and inactive systemic lupus erythematosus (SLE) and normal controls, and evaluate their significance as biomarkers for judging disease activity and therapeutic effect. Methods This was a single-center, observational cohort study in our hospital. The study time is from January 2021 to June 2022. The subjects were 90 SLE patients aged 15-70 and 22 healthy controls. Calculate systemic lupus erythematosus disease activity index (SLEDAI) to evaluate the overall disease activity; Patients with SLEDAI score>4 were regarded as active SLE, and the rest were classified as inactive SLE. The levels of CD4+CD28null T cells and PC4d were analyzed by flow cytometry. Results Compared with the healthy control group, the patients in active SLE group were younger, and the levels of CD4+CD28null T and PC4d were higher. The differences in WHO classification, SLEDAI, and CD4+CD28null T cells between patients with active SLE and those with inactive SLE were statistically significant. The levels of CD4+CD28null T and PC4d were positively correlated with SLEDAI (r=0.214, P<0.05; r=0.410, P<0.05). The difference in the percentage of CD4+CD28null T cells across different WHO classifications was statistically significant. and the percentage of CD4+CD28null T cells in WHO grade 5 was significantly higher than that in other grades. Compared with the group with treatment response, the levels of CD4+CD28null T and PC4d in the group without treatment response increased significantly. ROC curve showed that the AUC values of CD4+CD28null T and PC4d in predicting the treatment response of SLE in active stage were 0.759(95%CI: 0.604-0.914) and 0.923(95%CI: 0.832-1.000), respectively. Conclusion The expansion of CD4+CD28null T cell and the increase of PC4d level are closely related to the disease activity of SLE patients, and they can be used as potential candidate biomarkers to predict the treatment response of active SLE patients.
|
Received: 30 July 2024
|
|
|
|
|
[1] CROW M K.Pathogenesis of systemic lupus erythematosus: risks, mechanisms and therapeutic targets[J]. Ann Rheum Dis, 2023, 82(8) : 999-1014. [2] Youssef S R, Elsalakawy W A.First report of expansion of CD4+/CD28 null T-helper lymphocytes in adult patients with idiopathic autoimmune hemolytic anemia[J]. Hematol Transfus Cell Ther, 2021, 43(4) : 396-401. [3] Zenke S, Sica M P, Steinberg F, et al.Differential trafficking of ligands trogocytosed via CD28 versus CTLA4 promotes collective cellular control of co-stimulation[J]. Nat Commun, 2022, 13(1) : 6459. [4] Wu C S, Chyuan I T, Chiu Y L, et al.Preserved specific anti-viral T-cell response but associated with decreased lupus activity in SLE patients with cytomegalovirus infection[J]. Rheumatology, 2020, 59(11): 3340-3349. [5] Robert M, Scherlinger M.Platelets are a major player and represent a therapeutic opportunity in systemic lupus erythematosus[J]. Joint Bone Spine, 2024, 91(1) : 105622. [6] Gartshteyn Y, Conklin J, Petri M A, et al.Role of Platelet‐Bound C4d (PC4d) in Predicting Risk of Future Thrombotic Events in Systemic Lupus Erythematosus[J]. Arthritis Care Res, 2023, 75(10) : 2088-2095. [7] Bortoluzzi A, Chighizola C B, Fredi M, et al.The IMMENSE study: the interplay between iMMune and ENdothelial cells in mediating cardiovascular risk in systemic lupus erythematosus[J]. Front Immunol, 2020, 11: 572876. [8] Low E S H, Krishnaswamy G, Thumboo J. Comparing the 1997 update of the 1982 American College of Rheumatology (ACR-97) and the 2012 Systemic Lupus International Collaborating Clinics (SLICC-12) criteria for systemic lupus erythematosus (SLE) classification: which enables earlier classification of SLE in an urban Asian population?[J]. Lupus, 2019, 28(1) : 11-18. [9] Kandane-Rathnayake R, Kent J R, Louthrenoo W, et al.Longitudinal associations of active renal disease with irreversible organ damage accrual in systemic lupus erythematosus[J]. Lupus, 2019, 28(14) : 1669-1677. [10] GARTSHTEYN Y, CONKLIN J, PETRI M A, et al.Role of Platelet‐Bound C4d (PC4d) in Predicting Risk of Future Thrombotic Events in Systemic Lupus Erythematosus[J]. Arthritis Care Res (Hoboken) , 2023, 75(10) : 2088-2095. [11] 王红彦,李鑫铭,房柯池,等.系统性红斑狼疮疾病活动度相关特征分析及评估模型的构建[J].北京大学学报(医学版), 2024, 56(06): 1017-1022. [12] SAMPANI E, DAIKIDOU D V, LIOULIOS G, et al.CD28null and regulatory T cells are substantially disrupted in patients with end-stage renal disease due to diabetes mellitus[J]. Int J Mol Sci, 2021, 22(6) : 2975. [13] BÉZIAT V, RAPAPORT F, HU J, et al. Humans with inherited T cell CD28 deficiency are susceptible to skin papillomaviruses but are otherwise healthy[J]. Cell, 2021, 184 (14): 3812-3828. e30. [14] WANG T, WEI L, MENG S, et al.Coordinated priming of NKG2D pathway by IL-15 enhanced functional properties of cytotoxic CD4+ CD28-T cells expanded in systemic lupus erythematosus[J]. Inflammation, 2023, 46(5): 1587-1601. [15] AMEZCUA-GUERRA L M, ESPINOSA-BAUTISTA F, HOPF-ESTANDÍA K, et al. Senescent CD4+ CD28null cells are increased in chronic hyperuricemia, show aberrant effector phenotypes, and are reversed after allopurinol therapy: a proof-of-concept pilot study[J]. Clin Rheumatol, 2023, 42(8) : 2181-2186. [16] GUAN Y, CAO M, WU X, et al.CD28null T cells in aging and diseases: from biology to assessment and intervention[J]. Int Immunopharmacol, 2024, 131: 111807. [17] CIESIELSKA-FIGLON K, LISOWSKA K A.The Role of the CD28 Family Receptors in T-Cell Immunomodulation[J]. Int J Mol Sci, 2024, 25(2): 1274. [18] KOSMACZEWSKA A, CISZAK L, STOSIO M, et al.CD4+ CD28null T cells are expanded in moderately active systemic lupus erythematosus and secrete pro-inflammatory interferon gamma, depending on the Disease Activity Index[J]. Lupus, 2020, 29(7): 705-714. [19] HO C H, SILVA A A, TOMITA B, et al.Differential impacts of TNFα inhibitors on the transcriptome of Th cells[J]. Arthritis Res Ther, 2021, 23(1) : 199. [20] JIN S, YU C, YU B.Changes of serum IL-6, IL-10 and TNF-α levels in patients with systemic lupus erythematosus and their clinical value[J]. Am J Transl Res, 2021, 13(4) : 2867-2874. [21] RIOSERAS B, MORO-GARCÍA M A, GARCÍA-TORRE A, et al. Acquisition of new migratory properties by highly differentiated CD4+ CD28null T lymphocytes in rheumatoid arthritis disease[J]. J Pers Med, 2021, 11(7): 594. [22] ALEXANDER R V, REY D S, CONKLIN J, et al.A multianalyte assay panel with cell-bound complement activation products demonstrates clinical utility in systemic lupus erythematosus[J]. Lupus Sci Med, 2021, 8(1) : e000528. [23] GARTSHTEYN Y, MOR A, SHIMBO D, et al.Platelet bound complement split product (PC4d) is a marker of platelet activation and arterial vascular events in systemic lupus erythematosus[J]. Clin Immunol, 2021, 228: 108755. |
|
|
|