Increase in Double Negative B Lymphocytes in Patients with Systemic Lupus Erythematosus in Remission and Their Correlation with Early Differentiated T Lymphocyte Subpopulations
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Population
2.2. Flow Cytometry
2.3. Definition of Lymphocyte Subpopulations
- Early differentiated CD4 or CD8 lymphocytes that expressed:
- CD31, CD4+CD31+, and CD8+CD31+, defined as Recent Thymic Emigrants (RTE);
- CD45RA together with CCR7, CD4+CD45RA+CCR7+, and CD8+CD45RA+CCR7+, defined as naïve CD4 or CD8 lymphocytes;
- CD28 and not CD57, CD4CD28+CD57-, and CD8CD28+CD57-;
- CD45RA and not CD57, CD4CD45RA+CD57-, and CD8CD45RA+CD57-;
- Neither CD45RA nor CD57, CD4CD45RA-CD57-, and CD8CD45RA-CD57-.
- 2.
- In the group of memory cells, CD4 or CD8 lymphocytes that expressed:
- CCR7 and not CD45RA, CD4+CD45RA-CCR7+, and CD8+CD45RA-CCR7+, are defined as central memory (CM);
- Neither CCR7 nor CD45RA, CD4+CD45RA-CCR7- and CD8+CD45RA-CCR7-, are defined as effector memory (EM).
- 3.
- In the group of senescent/advanced differentiated cells:
- T cells expressing CD45RA and not CCR7, CD4+CD45RA+CCR7-, and CD8+CD45RA+CCR7-, are defined as EMRA;
- T cells lacking the CD28 molecule, CD4CD28-, and CD8CD28-, and their subtypes according to the presence of CD57, CD4+CD28-CD57-, CD4+CD28-CD57+, and CD8+CD28-CD57-, CD8+CD28-CD57+;
- T cells expressing both CD45RA and CD57, CD4CD45RA+CD57+, and CD8CD45RA+CD57+.
2.4. Statistical Analysis
3. Results
3.1. Characteristics of SLE Patients
3.2. Phenotypic Analysis of B Lymphocytes in Patients with SLE and in HC
3.3. Phenotypic Analysis of T Lymphocytes in SLE Patients and HC
3.4. Distribution of CD4 and CD8 Subtypes according to Their Differentiation Status
3.5. Correlation of DN B Cells with B Lymphocyte Subpopulations
3.6. Correlation of DN B Cells with T Lymphocyte Subpopulations
3.6.1. Correlation with CD4 Cells
3.6.2. Correlation with CD8 Cells
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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SLE | HC | p | |
---|---|---|---|
n | 30 | 31 | |
Laboratory results | |||
WCC (cells/μL) | 7200 ± 3350 | 6400 ± 1800 | NS |
Neutrophils (%) | 69.6 ± 20.7 | 58.1 ± 10.35 | <0.0001 |
Neutrophils (cells/μL) | 4600 ± 3500 | 3500 ± 1200 | 0.03 |
Lymphocytes (%) | 23.1 ± 16.1 | 25.6 ± 9 | 0.03 |
Lymphocytes (cells/μL) | 1400 ± 900 | 2100 ± 900 | 0.005 |
NLR | 3 ± 4 | 1.8 ± 0.85 | <0.0001 |
Ht (%) | 33 ± 9 | 39 ± 5 | 0.02 |
Hb (mg/dL) | 11.5 ± 6 | 13 ± 5 | 0.03 |
Platelets (103/μL) | 245 ± 96 | 270 ± 35 | NS |
CRP | 0.5 ± 0.4 | 0.4 ± 0.6 | NS |
Serum urea (mg/dL) | 36 ± 12 | 34 ± 5 | NS |
Serum creatinine (mg/dL) | 0.9 ± 0.5 | 0.87 ± 6 | NS |
Total protein (g/dL) | 7.5 ± 4 | 7.7 ± 3.2 | NS |
Serum albumin (g/dL) | 4.2 ± 2.3 | 4.6 ± 2.5 | NS |
SLE | HC | p | |
---|---|---|---|
n | 30 | 31 | |
CD19 (%) | 7.9 (2.1–28.6) | 11.8 (5.4–24) | 0.012 |
CD19 cells/μL | 75.4 (14.4–520.8) | 214 (84–576) | <0.001 |
IgD+CD27- (%) | 51.5 (0.4–94) | 58.7 (4.5–86.9) | 0.34 |
IgD+CD27- cells/μL | 37.71 (0.26–434.84) | 117 (5–364) | <0.001 |
IgD+CD27+ (%) | 3.9 (0.2–22) | 8.4 (1.5–44) | 0.014 |
IgD+CD27+ cells/μL | 5.12 (0.13–17.55) | 23 (2–700) | <0.001 |
IgD-CD27+ (%) | 19.1 (2.2–78) | 17.9 (7.1–71.9) | 0.7 |
IgD-CD27+ cells/μL | 18.58 (0.47–89.58) | 38 (11–258) | 0.001 |
IgD-CD27- (%) | 12.9 (2.3–74.2) | 8 (1.7–35) | 0.04 |
IgD-CD27- cells/μL | 10.84 (0.93–122.91) | 21 (3–202) | 0.007 |
Ratio DN/[ (IgD+CD27-) + (IgD-CD27+) + (IgD+CD27+)] | 0.14 (0.02–2.9) | 0.08 (0.02–0.54) | p = 0.04 |
SLE | HC | p | |
---|---|---|---|
n | 30 | 31 | |
CD4 (cells/μL) | 651.2 (71.1–1478.2) | 986 (344–1591) | 0.004 |
Early differentiated cells | |||
CD4+CD31+ | 216.38 (16.3–904.7) | 250 (69–967) | 0.14 |
CD4CD45RA+CD28+ | 267.97 (20.62–1030.31) | 388 (139–1402) | 0.02 |
CD4CD45RA+CD57- | 254.03 (21.05–1077.61) | 401 (160–1373) | 0.035 |
CD4CD45RA-CD57- | 290.67 (38.96–884.43) | 539 (173–991) | <0.001 |
CD4CD28+CD57- | 610.7 (54.68–1461.94) | 958 (332–1569) | 0.004 |
CD4CD28+CD57+ | 4.7 (0–806) | 7 (0–245) | 0.21 |
Memory cells | |||
CD4CD45RA-CCR7+ | 402.35 (38.7–972.4) | 563 (40–1001) | 0.046 |
CD4CD45RA-CCR7- | 1.62 (0–73.49) | 11 (0–590) | 0.002 |
Advanced differentiated/senescent cells | |||
CD45RA+CCR7- | 7.29 (0–180.62) | 23 (0–487) | 0.027 |
CD4CD28- | 20.12 (1.27–139.06) | 38 (3–299) | 0.04 |
CD4CD28-CD57+ | 9.90 (0.46–73.8) | 23 (0–274) | 0.1 |
CD45RA+CCR7-CD28- | 1.2 (0–82) | 2.5 (0–106) | 0.21 |
SLE | HC | p | |
---|---|---|---|
n | 30 | 31 | |
CD8 (cells/μL) | 414.8 (60.6–2017.8) | 454.5 (154–1310) | 0.26 |
Early differentiated cells | |||
CD8+CD31+ | 88.19 (8.2–1047) | 187.5 (8–541) | 0.26 |
CD8CD45RA+CD28+ | 113.56 (1.81–753.7) | 212.5 (7–1257) | 0.17 |
CD8CD45RA+CD57- | 63.65 (3.83–889.8) | 133 (8–552) | 0.17 |
CD8CD45RA-CD57- | 194.52 (1.8–945.1) | 179 (28–555) | 0.99 |
CD8CD28+CD57- | 249.45 (5.49–1362) | 298 (95–646) | 0.1 |
CD8CD28+CD57+ | 12(0.4–132) | 8.5 (0–424) | 0.58 |
Memory cells | |||
CD8CD45RA-CCR7+ | 171.52 (2.5–1417) | 123 (1–941) | 0.14 |
CD8CD45RA-CCR7- | 13.94 (0.59–92.37) | 25 (0–355) | 0.53 |
Advanced differentiated/senescent cells | |||
CD8CD45RA+CCR7- | 11.13 (0–279.6) | 49.5 (0–534) | 0.02 |
CD8CD28- | 87.83 (4.56–1361.2) | 135 (36–633) | 0.14 |
CD8CD28-CD57+ | 53.17 (0.83–571.04) | 71 (0–470) | 0.17 |
CD45RA+CCR7-CD28- | 37.3 (2.1–263) | 197 (9–783) | <0.0001 |
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Moysidou, E.; Lioulios, G.; Christodoulou, M.; Xochelli, A.; Stai, S.; Iosifidou, M.; Iosifidou, A.; Briza, S.; Briza, D.I.; Fylaktou, A.; et al. Increase in Double Negative B Lymphocytes in Patients with Systemic Lupus Erythematosus in Remission and Their Correlation with Early Differentiated T Lymphocyte Subpopulations. Curr. Issues Mol. Biol. 2023, 45, 6667-6681. https://doi.org/10.3390/cimb45080421
Moysidou E, Lioulios G, Christodoulou M, Xochelli A, Stai S, Iosifidou M, Iosifidou A, Briza S, Briza DI, Fylaktou A, et al. Increase in Double Negative B Lymphocytes in Patients with Systemic Lupus Erythematosus in Remission and Their Correlation with Early Differentiated T Lymphocyte Subpopulations. Current Issues in Molecular Biology. 2023; 45(8):6667-6681. https://doi.org/10.3390/cimb45080421
Chicago/Turabian StyleMoysidou, Eleni, Georgios Lioulios, Michalis Christodoulou, Aliki Xochelli, Stamatia Stai, Myrto Iosifidou, Artemis Iosifidou, Sophia Briza, Dimitria Ioanna Briza, Asimina Fylaktou, and et al. 2023. "Increase in Double Negative B Lymphocytes in Patients with Systemic Lupus Erythematosus in Remission and Their Correlation with Early Differentiated T Lymphocyte Subpopulations" Current Issues in Molecular Biology 45, no. 8: 6667-6681. https://doi.org/10.3390/cimb45080421