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Lymphocyte subset clustering analysis in treatment-naive patients with systemic lupus erythematosus

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Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Objectives

The aim of the study is to identify clusters of lymphocyte subsets within treatment-naive systemic lupus erythematosus (SLE) patients and evaluate the potential association of these clusters with disease activities.

Methods

We conducted a cross-sectional study of consecutive 143 treatment-naive SLE patients in the Affiliated Hospital of Nantong University, China. We used hierarchical cluster analysis to classify individuals into clusters based on circulating lymphocyte subset proportions (CD3+CD4+T cell, CD3+CD8+T cell, CD19+B cell, and CD3-CD16 + CD56 NK cell) via R software. Demographic variables, clinical manifestations, laboratory variables, and disease activities were compared among clusters.

Results

The SLE patients (median age 35 (26–48) years, 90.9% female) were divided into four clusters. The clustering features were as follows: cluster 1 (B high), cluster 2 (CD4 high), cluster 3 (CD8 high), and cluster 4 (NK high). SLE patients in cluster 1 showed the highest incidence of arthritis (70.6%, 34.2%, 48.3%, and 42.9% in clusters 1, 2, 3, and 4, respectively; P = 0.046), and patients in cluster 3 and cluster 4 showed significantly a higher incidence of nephritis (35.3%, 25.0%, 48.3%, and 61.9% in in clusters 1, 2, 3, and 4, respectively; P = 0.008). Patients in cluster 2 suffered from lower SLE Disease Activity Index (SLEDAI) score (12.1 ± 5.0, 10.3 ± 5.6, 12.2 ± 4.6, and 14.4 ± 7.3 in clusters 1, 2, 3, and 4, respectively; P = 0.046). Regression analysis indicated that, compared with patients in cluster 2, patients in cluster 1 exhibited higher rate of arthritis (OR 4.53, 95% CI 1.38–14.86, P = 0.013), while patients in cluster 3 (OR 2.85, 95%CI 1.15–7.08, P = 0.024) and cluster 4 (OR 4.93, 95%CI 1.76–13.85, P = 0.002) exhibited higher rate of nephritis.

Conclusion

This study supports the existence of lymphocyte subset clusters with different clinical features in treatment-naive SLE patients, which could help to differentiate between various subsets of SLE.

Key Points

• Lymphocyte subsets may occur in a pattern of cluster in treatment-naive SLE patients.

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Acknowledgments

We thank all patients and healthy donors controls involved in the study.

Funding

This work was supported by the National Natural Science Foundation of China (Grant Nos. 81671606, 81601410), the Liaoning Distinguished Professor program (Liao taught 2018 to 2020), Dalian key laboratory of human homeostasis microbiology and disease immunology. Special Fund for Clinical Medicine, Nantong Science and Technology Bureau (Grant Nos. HS2014071 and HS2016003); Jiangsu Provincial Commission of Health and Family Planning (Grant No. H201623); and Nantong 226 Talents Project (Grant No. 2017-13).

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Authors and Affiliations

  1. Department of Immunology, College of Basic Medical Science, Dalian Medical University, Dalian, People’s Republic of China

    Zhimin Lu, Weiping Li, Yawei Tang & Xia Li

  2. Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, People’s Republic of China

    Zhimin Lu & Zhanyun Da

  3. Department of Hematopathology, The Second Hospital of Dalian Medical University, Dalian, People’s Republic of China

    Weiping Li

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  1. Zhimin Lu
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Correspondence to Zhanyun Da or Xia Li.

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This study was approved by the Ethics Committee of the Affiliated Hospital of Nantong University.

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Zhimin Lu and Weiping Li are the co-first authors.

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Lu, Z., Li, W., Tang, Y. et al. Lymphocyte subset clustering analysis in treatment-naive patients with systemic lupus erythematosus. Clin Rheumatol 40, 1835–1842 (2021). https://doi.org/10.1007/s10067-020-05480-y

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