CD200 and CD200R Expression on Peripheral Blood Lymphocytes and Serum CD200 Concentration as a New Marker of Endometriosis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients and Controls
2.2. Material Collection
2.3. Immunophenotyping
2.4. Measurement of sCD200 Concentration
2.5. Measurement of Cancer Antigen 125 (CA-125) and Human Epididymis Protein 4 (HE-4) Level
2.6. Statistical Analysis
3. Results
3.1. Patients and Controls
3.2. Frequencies of White Blood Cells and Basic Lymphocyte Subsets in EMS Patients and Controls
3.3. Frequencies of CD200 and CD200R Expression on T and B Lymphocyte Subsets and Concentration of sCD200 in EMS Patients and Controls
3.4. Frequencies of CD200 and CD200R on T and B Lymphocyte Subsets in Patients with Different Types of EMS
3.5. Frequencies of CD200 and CD200R on T and B Lymphocyte Subsets in Patients with EMS and Adhesions, Infertility, or Dysmenorrhea
3.6. Correlations between CD200 and CD200R Expression on T and B Lymphocyte Subsets and Selected Laboratory Parameters in EMS Patients
3.7. Correlations between CD200 and CD200R Expression on T and B Lymphocyte Subsets in EMS Patients and the Stage of the Disease
3.8. Univariate and Multivariate Analyses for the Identification of Risk Factors Associated with EMS
3.9. Receiver Operating Characteristic (ROC) Curve Comparing the Sensitivity and Specificity of CD200 and CD200R in EMS Patients
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AML | acute myeloid leukemia |
BMI | body mass index |
Ca-125 | cancer antigen 125 |
CD4+ | cluster of differentiation 4+ |
CD200 | cluster of differentiation-200 |
CD200R | receptor of cluster of differentiation-200 |
CD200tg | CD200 transgene |
DCs | dendritic cells |
EDTA | ethylenediaminetetraacetic acid |
EMS | endometriosis |
HE-4 | |
IDO | indoleamine-pyrrole 2,3-dioxygenase |
Ig | immunoglobulin |
Ig SF | immunoglobulin superfamily |
kDA | kilodaltons |
LYM | lymphocytes |
MON | monocytes |
N/A | not applicable |
NEU | neutrophils |
NS | not significant |
NK | natural killer cells |
PB | peripheral blood |
PD-1 | programmed death-1 |
PD-L1 | programmed death ligand-1 |
PF | peritoneal fluid |
ROC | receiver operating characteristic |
sCD200 | soluble CD200 |
Th | T helper cells |
Tregs | T regulatory cells |
WBC | white blood cells |
Appendix A
References
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Parameter | EMS (n = 54) | CONTROL (n = 20) | p-Value |
---|---|---|---|
Age [years] mean ± SD | 35.00 ± 6.19 | 36.65 ± 6.87 | NS |
Disease stage: | N/A | - | |
I | 31.48% (n = 17) | ||
II | 31.48% (n = 17) | ||
III–IV | 37.04% (n = 20) | ||
Adhesions | 57.41% (n = 31) | N/A | - |
Dysmenorrhea | 79.63% (n = 43) | N/A | - |
Infertility | 50.00% (n = 27) | N/A | - |
CA-125 [U/mL] mean ± SD | 37.79 ± 28.95 | 9.23 ± 5.37 | p < 0.005 |
HE-4 [pmol/L] mean ± SD | 39.96 ± 9.69 | 37.05 ± 9.14 | NS |
TSH serum concentration [µlU/mL] mean ± SD | 1.38 ± 0.63 | 1.43 ± 0.69 | NS |
FT3 serum concentration [pg/mL] mean ± SD | 3.15 ± 0.57 | 3.13 ± 0.58 | NS |
FT4 serum concentration [ng/mL] mean ± SD | 1.31 ± 0.24 | 1.30 ± 0.22 | NS |
Estradiol serum concentration [pg/mL] mean ± SD | 57.93 ± 26.43 | 56.23 ± 27.43 | NS |
FSH serum concentration [mlU/mL] mean ± SD | 5.37 ± 1.80 | 6.17 ± 1.58 | NS |
LH serum concentration [mlU/mL] mean ± SD | 6.64 ± 2.76 | 5.96 ± 1.82 | NS |
BMI [kg/m2] mean ± SD | 21.8 ± 2.12 | 21.87 ± 1.84 | NS |
Parameter | EMS (n = 54) | CONTROL (n = 20) | p-Value | ||
---|---|---|---|---|---|
Mean ± SD | Median (Range) | Mean ± SD | Median (Range) | ||
WBC (103/mm3) (normal range: 4.0–10.0) | 8.36 ± 1.58 | 8.26 (5.51–11.33) | 7.42 ± 0.77 | 7.31 (6.37–8.66) | 0.015 |
LYM (103/mm3) (normal range: 1.12–4.73) | 2.24 ± 0.73 | 2.06 (1.20–3.83) | 2.44 ± 0.45 | 2.54 (1.53–3.07) | NS |
NEU (103/mm3) (normal range: 1.12–4.73) | 5.04 ± 1.40 | 5.50 (2.08–7.91) | 4.32 ± 1.03 | 3.94 (2.71–6.03) | 0.015 |
MON (103/mm3) (normal range: 1.12–4.73) | 0.54 ± 0.17 | 0.56 (0.24–0.86) | 0.47 ± 0.09 | 0.49 (0.28–0.59) | 0.054 |
CD3+ T lymphocytes (%) | 70.83 ± 4.63 | 71.86 (61.31–78.77) | 68.26 ± 3.84 | 68.08 (60.63–74.49) | 0.021 |
CD19+ B lymphocytes (%) | 10.55 ± 3.11 | 9.76 (6.12–16.84) | 11.25 ± 2.50 | 11.40 (6.04–16.90) | NS |
CD3+/CD4+ T lymphocytes (%) | 43.09 ± 7.64 | 44.01 (26.13–65.45) | 44.46 ± 2.51 | 44.16 (40.71–48.84) | NS |
CD3+/CD8+ T lymphocytes (%) | 28.07 ± 6.85 | 27.99 (16.25–42.90) | 34.36 ± 3.29 | 34.74 (29.33–39.60) | <0.005 |
T CD3+/CD4+: T CD3+/CD8+ lymphocyte ratio | 1.67 ± 0.65 | 1.59 (0.67–3.88) | 1.31 ± 0.16 | 1.29 (1.03–1.57) | 0.016 |
T regulatory cells CD4+/CD25+/FOXP3 (%) | 6.30 ± 3.16 | 5.46 (0.39–13.55) | 6.20 ± 2.02 | 6.25 (3.13–9.68) | NS |
NK cells CD3-CD16+CD56+ (%) | 10.31 ± 4.30 | 10.26 (2.34–20.43) | 15.35 ± 2.25 | 14.43 (12.16–19.34) | <0.001 |
NKT-like cells CD3+/CD16+/CD56+ (%) | 3.40 ± 2.85 | 2.27 (0.21–11.26) | 3.02 ± 1.02 | 3.27 (1.15–4.92) | NS |
Parameter | EMS (n = 54) | CONTROL (n = 20) | p-Value | ||
---|---|---|---|---|---|
Mean ± SD | Median (Range) | Mean ± SD | Median (Range) | ||
CD19+CD200+ B lymphocytes (%) | 81.81 ± 11.58 | 79.90 (60.39–99.99) | 76.16 ± 6.55 | 76.59 (67.39–93.19) | 0.04 |
CD4+CD200+ T lymphocytes (%) | 10.55 ± 3.11 | 9.76 (6.12–16.84) | 11.25 ± 2.50 | 11.40 (6.04–16.90) | <0.001 |
CD8+CD200+ T lymphocytes (%) | 9.42 ± 6.23 | 7.40 (1.88–28.04) | 3.88 ± 1.56 | 3.66 (0.35–6.45) | <0.001 |
CD19+CD200R+ B lymphocytes (%) | 10.92 ± 3.82 | 11.05 (4.15–20.05) | 25.02 ± 4.06 | 24.80 (16.91–31.89) | <0.001 |
CD4+CD200R+ T lymphocytes (%) | 14.60 ± 7.87 | 14.44 (3.23–40.71) | 23.12 ± 7.95 | 22.28 (7.39–38.83) | <0.001 |
CD8+CD200R+ T lymphocytes (%) | 9.19 ± 6.07 | 8.51 (0.59–36.84) | 14.38 ± 5.78 | 13.24 (6.03–31.92) | <0.001 |
sCD200 serum level (pg/mL) | 964.85 ± 682.92 | 742.05 (63.82–3037.54) | 1774.53 ± 1185.13 | 1339.94 (513.81–4784.76) | 0.001 |
Parameter | Endometrioma (Mean ± SD/Median; Range) | DIE (Mean ± SD/Median; Range) | Peritoneal Endometriosis (Mean ± SD/Median; Range) | ||||||
---|---|---|---|---|---|---|---|---|---|
Positive (n = 30) | Negative (n = 24) | p-Value | Positive (n = 11) | Negative (n = 43) | p-Value | Positive (n = 35) | Negative (n = 19) | p- Value | |
CD19+CD200+ B lymphocytes (%) | 79.24 ± 12.36/ 78.6; 60.4–99.99 | 85.01 ± 9.86/ 82.6; 66.7–99.99 | 0.049 | 92.46 ± 12.06/ 99.2; 69.2–99.99 | 79.08 ± 9.9/79.1; 60.4–99.99 | 0.00034 | 84.3 ± 10.3/82.8; 64.6–99.99 | 77.3 ± 12.7/ 74.9; 60.4–99.99 | 0.029 |
CD4+CD200+ T lymphocytes (%) | 11.37 ± 5.25/ 10.5; 3.5–24.3 | 12.95 ± 7.2/ 11.3; 4.3–34.7 | 0.53 | 15.02 ± 8.77/ 13.6; 3.5–34.7 | 11.32 ± 5.2/ 9.98; 4.3–26.1 | 0.076 | 11.8 ± 6.3/ 9.4; 3.5–34.7 | 12.6 ± 5.3/ 12.4; 4.6–24.3 | 0.33 |
CD8+CD200+ T lymphocytes (%) | 9.48 ± 5.7/ 7.4; 2.3–25.1 | 9.36 ± 6.97/ 7.6; 1.2–28.0 | 0.53 | 15.24 ± 7.54/ 16.3; 2.3–28.0 | 7.94 ± 4.9/ 6.3; 1.9–25.1 | 0.00027 | 8.5 ± 6.3/ 6.6; 1.9–28.0 | 11.1 ± 5.9/ 12.2; 3.3–25.1 | 0.057 |
CD19+CD200R+ B lymphocytes (%) | 9.98 ± 3.56/ 10.0; 4.2–20.1 | 12.1 ± 3.9/ 11.7; 5.3–19.2 | 0.05 | 11.66 ± 3.67/ 11.6; 6.7–17.8 | 10.73 ± 3.9/ 10.8; 4.2–20.1 | 0.48 | 11.4 ± 3.8/ 11.2; 5.3–20.1 | 10.0 ± 3.9/ 10.4; 4.2–17.8 | 0.25 |
CD4+CD200R+ T lymphocytes (%) | 15.36 ± 9.02/ 14.5; 3.2–40.7 | 13.66 ± 6.19/ 13.9; 3.9–23.8 | 0.18 | 13.3 ± 5.36/ 14.4; 4.3–20.7 | 14.94 ± 8.4/ 14.5; 3.2–40.7 | 0.54 | 13.9 ± 6.4/ 14.4; 3.2–29.9 | 15.9 ± 10.1/ 14.5; 4.3–40.7 | 0.77 |
CD8+CD200R+ T lymphocytes (%) | 9.24 ± 7.26/ 7.6; 0.6–36.8 | 9.12 ± 4.3/ 9.3; 2.3–17.2 | 0.67 | 12.28 ± 3.67/ 12.1; 5.5–17.2 | 8.40 ± 6.4/ 6.9; 0.6–36.8 | 0.058 | 9.4 ± 6.3/ 8.6; 1.6–36.8 | 8.8 ± 5.7/ 6.9; 0.6–18.9 | 0.94 |
sCD200 serum level (pg/mL) | 1091.21 ± 689.1/ 881.9; 63.8–3037.5 | 806.9 ± 655.1/5 48.8; 125.6–2667.9 | 0.021 | 1029.63 ± 850.0/ 611.0; 506.7–3037.5 | 948.28 ± 644.3/ 816.3; 63.8–2960.3 | 0.76 | 903.6 ± 612.5/ 751.0; 125.6–2667.9 | 1077.7 ± 802.4/ 733.1; 63.8–3037.5 | 0.49 |
Parameter | Adhesions (Mean ± SD/Median; Range) | Pelvic pain (Mean ± SD/Median; Range) | Infertility (mean ± SD/Median; Range) | ||||||
---|---|---|---|---|---|---|---|---|---|
Positive (n = 31) | Negative (n = 23) | p-Value | Positive (n = 43) | Negative (n = 11) | p-Value | Positive (n = 27) | Negative (n = 27) | p-Value | |
CD19+CD200+ B lymphocytes (%) | 85.3 ± 11.7/ 80.7; 65.9–99.99 | 77.1 ± 9.9/ 79.1; 60.4–92.7 | 0.024 | 83.0 ± 12.2/ 79.9; 63.5–99.99 | 77.3 ± 7.8/ 79.9; 60.4–88.6 | 0.27 | 80.3 ± 10.2/ 79.9; 64.2–99.9 | 83.3 ± 12.8/ 79.5; 60.4–99.99 | 0.47 |
CD4+CD200+ T lymphocytes (%) | 13.6 ± 7.2/ 12.4; 3.5–34.7 | 10.0 ± 3.8/ 9.1; 4.3–18.9 | 0.077 | 12.8 ± 6.6/ 11.1; 3.5–34.7 | 9.4 ± 2.8/ 8.8; 4.6–13.5 | 0.11 | 12.4 ± 6.2/ 10.1; 5.2–34.7 | 11.7 ± 6.2/ 10.8; 3.5–26.1 | 0.56 |
CD8+CD200+ T lymphocytes (%) | 11.5 ± 6.8/ 9.8; 2.3–28.0 | 6.7 ± 4.0/ 5.3; 1.9–15.0 | 0.0056 | 10.3 ± 6.5/ 8.3; 1.9–28.0 | 6.1 ± 3.6/ 4.5; 2.9–14.1 | 0.057 | 9.0 ± 5.6/ 7.1; 2.9–14.0 | 9.8 ± 6.8/ 7.5; 1.9–28.0 | 0.84 |
CD19+CD200R+ B lymphocytes (%) | 10.1 ± 3.8/ 9.1; 4.2–20.1 | 12.0 ± 3.7/ 12.2; 5.4–19.2 | 0.059 | 10.6 ± 3.8/ 10.5; 4.2–20.1 | 12.2 ± 3.7/ 11.2; 6.0–19.2 | 0.22 | 11.2 ± 3.9/ 11.2; 5.2–19.2 | 10.7 ± 3.8/ 11.0; 4.2–20.1 | 0.63 |
CD4+CD200R+ T lymphocytes (%) | 15.4 ± 8.4/ 15.0; 3.2–40.7 | 13.5 ± 7.2/ 12.7; 3.9–29.9 | 0.38 | 15.0 ± 8.3/ 14.8; 3.2–40.7 | 12.9 ± 5.7/ 12.7; 5.2–22.7 | 0.48 | 13.8 ± 6.9/ 13.5; 3.9–29.9 | 15.4 ± 8.8/ 14.5; 3.2–40.7 | 0.74 |
CD8+CD200R+ T lymphocytes (%) | 10.7 ± 6.8/ 10.7; 0.6–36.8 | 7.1 ± 4.3/ 6.2; 2.1–15.3 | 0.024 | 9.9 ± 6.2/ 8.9; 0.6–36.8 | 6.6 ± 4.8/ 4.9; 1.2–13.0 | 0.071 | 9.4 ± 5.2/ 10.1; 2.1–18.9 | 8.9 ± 6.9/ 8.2; 0.6–36.8 | 0.43 |
sCD200 serum level (pg/mL) | 972.1 ± 733.4/ 732.5; 63.8–3037.5 | 955.1 ± 624.4/ 889.0; 125.6–2667.9 | 0.81 | 1035.1 ± 731.9/ 751.0; 63.8–3037.5 | 690.0 ± 342.5/ 649.0; 140.2–1214.0 | 0.28 | 1019.9 ± 772.8/ 816.3; 125.6–3037.5 | 909.8 ± 589.2/ 733.1; 63.8–2960.3 | 0.89 |
Correlation between the Stage of Ems and Lymphocytes Expressing CD200 or CD200R | R | p-Value |
---|---|---|
CD19 + CD200+ B lymphocytes (%) | 0.273 | 0.045 |
CD4 + CD200 + T lymphocytes (%) | 0.183 | 0.185 |
CD8 + CD200 + T lymphocytes (%) | 0.522 | <0.001 |
CD19 + CD200R + B lymphocytes (%) | −0.076 | 0.583 |
CD4 + CD200R + T lymphocytes (%) | 0.015 | 0.913 |
CD8 + CD200R + T lymphocytes (%) | 0.400 | 0.003 |
Parameter | Univariate Analysis | Multivariate Analysis | ||
---|---|---|---|---|
OR (95% CI) | p Value | OR (95% CI) | p Value | |
Age [years] | 0.96 (0.89–1.0) | 0.32 | ||
BMI (kg/m2) | 0.98 (0.76–1.3) | 0.89 | ||
CA-125 concentration [U/mL] | 1.31 (1.1–1.5) | 0.0004 | 1.42 (1.1–1.8) | 0.004 |
HE4 concentration [pmol/L] | 1.04 (0.98–1.1) | 0.25 | ||
CD19+CD200+ B lymphocytes (%) | 1.06 (1.0–1.12) | 0.0496 | ||
CD4+CD200+ T lymphocytes (%) | 1.78 (1.3–2.4) | 0.0001 | 1.71 (1.2–6.1) | 0.016 |
CD8+CD200+ T lymphocytes (%) | 1.58 (1.2–2.1) | 0.0035 | ||
CD19+CD200R+ B lymphocytes (%) | 0.39 (0.20–0.76) | 0.0059 | ||
CD4+CD200R+ T lymphocytes (%) | 0.88 (0.82–0.95) | 0.0009 | ||
CD8+CD200R+ T lymphocytes (%) | 0.87 (0.78–0.96) | 0.0077 | ||
sCD200 serum level (pg/mL) | 0.99 (0.998–1.0) | 0.0034 |
Parameter | AUC | 95% CI | PPV | NPV | LR(+) | LR(−) | ACC | p-Value * |
---|---|---|---|---|---|---|---|---|
CD4+/CD200 + lymphocytes [%] | 0.895 | 0.82–0.969 | 92.7 | 54.5 | 3.09 | 0.42 | 0.656 | p < 0.0001 |
CD8+/CD200 + lymphocytes [%] | 0.804 | 0.706–0.903 | 90.3 | 45.1 | 2.80 | 0.51 | 0.618 | p < 0.0001 |
CD19+/CD200 + lymphocytes [%] | 0.653 | 0.528–0.778 | 84.3 | 30.5 | 2.29 | 0.77 | 0.566 | p = 0.0165 |
CD4+/CD200R + lymphocytes [%] | 0.800 | 0.684–0.917 | 88.4 | 44.6 | 3.11 | 0.52 | 0.622 | p < 0.0001 |
CD8+/CD200R + lymphocytes [%] | 0.761 | 0.651–0.872 | 88.3 | 41.8 | 2.92 | 0.55 | 0.606 | p < 0.0001 |
CD19+/CD200R + lymphocytes [%] | 0.994 | 0.984–1.0 | 95.6 | 62.0 | 5.34 | 0.36 | 0.698 | p < 0.0001 |
sCD200 concentration [pg/mL] | 0.750 | 0.632–0.868 | 87.3 | 43.3 | 3.16 | 0.55 | 0.602 | p < 0.0001 |
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Abramiuk, M.; Grywalska, E.; Korona-Głowniak, I.; Niedźwiedzka-Rystwej, P.; Polak, G.; Kotarski, J.; Roliński, J. CD200 and CD200R Expression on Peripheral Blood Lymphocytes and Serum CD200 Concentration as a New Marker of Endometriosis. J. Clin. Med. 2020, 9, 3035. https://doi.org/10.3390/jcm9093035
Abramiuk M, Grywalska E, Korona-Głowniak I, Niedźwiedzka-Rystwej P, Polak G, Kotarski J, Roliński J. CD200 and CD200R Expression on Peripheral Blood Lymphocytes and Serum CD200 Concentration as a New Marker of Endometriosis. Journal of Clinical Medicine. 2020; 9(9):3035. https://doi.org/10.3390/jcm9093035
Chicago/Turabian StyleAbramiuk, Monika, Ewelina Grywalska, Izabela Korona-Głowniak, Paulina Niedźwiedzka-Rystwej, Grzegorz Polak, Jan Kotarski, and Jacek Roliński. 2020. "CD200 and CD200R Expression on Peripheral Blood Lymphocytes and Serum CD200 Concentration as a New Marker of Endometriosis" Journal of Clinical Medicine 9, no. 9: 3035. https://doi.org/10.3390/jcm9093035