Quantification of Antiphospholipid Antibodies: The Importance of Using an Appropriate Methodology for Each Clinical Profile
Abstract
:1. Introduction
2. Results
2.1. Study Population
2.2. Method Comparison
aPL | M1 and M2 Positives | M1 Positives | M2 Positives | Kappa Index | 95% CI | Level of Agreement |
---|---|---|---|---|---|---|
aCL IgG | 24 | 32 | 31 | 0.40 | 0.28–0.52 | Fair |
aCL IgM | 18 | 35 | 40 | 0.28 | 0.17–0.40 | Fair |
aβ2GPI IgG | 28 | 25 | 29 | 0.48 | 0.36–0.60 | Moderate |
aβ2GPI IgM | 23 | 18 | 36 | 0.43 | 0.31–0.56 | Moderate |
2.3. Lupus Anticoagulant
2.4. Patients with APS Associated Clinical Events
2.5. Correlation between Methodologies According to Clinical Events
Clinical Manifestation | Number of Patients | M1 and M2 Positives | M1 Positives | M2 Positives | Kappa Index | 95% CI | Level of Agreement |
---|---|---|---|---|---|---|---|
Any Sidney APS clinical criteria | 403 | 27 | 42 | 24 | 0.36 | 0.23–0.48 | Fair |
Gestational only | 74 | 7 | 11 | 1 | 0.46 | 0.21–0.70 | Moderate |
Gestational | 80 | 8 | 11 | 2 | 0.45 | 0.21–0.69 | Moderate |
Thrombotic and gestational | 6 | 1 | 0 | 1 | 0.57 | −0.12–1.00 | No agreement |
Thrombotic only | 323 | 19 | 31 | 22 | 0.32 | 0.18–0.46 | Fair |
Thrombotic | 329 | 20 | 31 | 23 | 0.33 | 0.19–0.47 | Fair |
2.6. Patients with Other Autoimmune Disease
2.7. Importance of Antibody Titres
2.8. Diagnostic Performance
3. Discussion
4. Materials and Methods
4.1. Study Design
4.2. Cut-Off Established Using Healthy Donors
4.3. Assays
4.4. Statistical Methods
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Study Population (n = 1020) | ||
---|---|---|
Variables | Median (SD)/n | IQR/% |
Age | 56 (19.13) | 41–70 |
Sex (Male) | 398 | 39.0 |
Dyslipidemia | 247 | 24.2 |
Diabetes mellitus | 151 | 14.8 |
Smoking | 239 | 23.4 |
High blood pressure | 324 | 31.8 |
Clinical manifestations included in APS classification criteria | 403 | 39.5 |
Thrombotic events | 329 | 81.64 |
Obstetric events | 80 | 19.85 |
Autoimmune diseases | 172 | 16.9 |
SLE | 64 | 37.2 |
RA | 36 | 20.9 |
SS | 23 | 13.4 |
SScl | 20 | 11.6 |
APS Events (n = 403) | No APS Events (n = 617) | |||
---|---|---|---|---|
aPL | Correlation Coefficient | p-Value | Correlation Coefficient | p-Value |
aβ2GPI IgM | 0.80 | <0.0001 | 0.64 | <0.0001 |
aCL IgM | 0.46 | <0.0001 | 0.18 | <0.0001 |
aβ2GPI IgG | 0.61 | <0.0001 | 0.37 | <0.0001 |
aCL IgG | 0.71 | <0.0001 | 0.49 | <0.0001 |
Thrombotic Events (n = 329) | Gestational Events (n = 80) | |||
---|---|---|---|---|
aPL | Correlation Coefficient | p-Value | Correlation Coefficient | p-Value |
aβ2GPI IgM | 0.84 | <0.0001 | 0.81 | <0.0001 |
aCL IgM | 0.50 | <0.0001 | 0.48 | <0.0001 |
aβ2GPI IgG | 0.60 | <0.0001 | 0.66 | <0.0001 |
aCL IgG | 0.70 | <0.0001 | 0.66 | <0.0001 |
Autoimmune Disease | Non-Autoimmune Disease | p-Value | |
---|---|---|---|
APS related event | 0.55 (0.28–0.83) | 0.30 (0.17–0.44) | 0.110 |
Non-APS related event | 0.55 (0.32–0.77) | 0.37 (0.23–0.20) | 0.182 |
AUC | |
---|---|
M1 and thrombotic events | Non-significant (p = 0.16) |
M2 and thrombotic events | 0.52 (0.5–0.54) |
M1 and obstetric morbidity considering only females | 0.57 (0.52–0.62) |
M2 and obstetric morbidity considering only females | Non-significant (p = 0.49) |
M1 | M2 | ||||
---|---|---|---|---|---|
Sensitivity | Specificity | Sensitivity | Specificity | ||
All patients | APS event | 17.12 (13.57–21.16) | 89.30 (86.59–91.63) | 12.66 (9.57–16.30) | 91.41 (88.91–93.50) |
Thrombotic event | 15.50 (11.76–19.87) | 87.84 (85.17–90.19) | 13.07 (9.62–17.20) | 91.17 (88.80–93.18) | |
Obstetric event | 23.75 (14.95–34.58) | 87.66 (85.39–89.69) | 12.50 (6.16–21.79) | 90.00 (87.90–91.84) | |
Autoimmune disease | APS event | 27.66 (15.62–42.64) | 88.00 (80.98–93.13) | 23.40 (12.30–38.03) | 88.80 (81.98–93.73) |
Thrombotic event | 22.50 (10.84–38.45) | 85.61 (78.44–91.11) | 22.50 (10.84–38.45) | 87.88 (81.14–92.87) | |
Obstetric event | 50.00 (17.70–84.30) | 85.37 (79.01–90.39) | 25.00 (3.19–65.09) | 85.98 (79.70–90.90) | |
No autoimmune disease | APS event | 15.73 (12.11–19.94) | 89.63 (86.60–92.18) | 11.24 (8.15–14.98) | 92.07 (89.32–94.30 |
Thrombotic event | 14.53 (10.68–19.13) | 88.37 (85.42–90.91) | 11.76 (8.29–16.05) | 91.95 (89.38–94.07) | |
Obstetric event | 20.83 (12.16–32.02) | 88.14 (85.66–90.33) | 11.11 (4.92–20.72) | 90.85 (88.60–92.79) |
M1 | M2 | ||||
---|---|---|---|---|---|
Positive Likelihood Ratio | Negative Likelihood Ratio | Positive Likelihood Ratio | Negative Likelihood Ratio | ||
All patients | APS event | 1.6 (1.17–2.19) | 0.93 (0.88–0.98) | 1.47 (1.02–2.12) | 0.96 (0.91–1) |
Thrombotic event | 1.28 (0.92–1.76) | 0.96 (0.91–1.02) | 1.48 (1.03–2.14) | 0.95 (0.91–1) | |
Obstetric event | 1.92 (1.25–2.95) | 0.87 (0.77–0.99) | 1.25 (0.68–2.30) | 0.97 (0.89–1.06) | |
Autoimmune disease | APS event | 2.3 (1.19–4.47) | 0.82 (0.68–0.99) | 1.95 (0.97–3.94) | 0.87 (0.73–1.03) |
Thrombotic event | 1.56 (0.77–3.18) | 0.91 (0.76–1.08) | 1.75 (0.84–3.61) | 0.89 (0.74–1.06) | |
Obstetric event | 3.42 (1.56–7.49) | 0.59 (0.29–1.17) | 1.71 (0.49–6) | 0.88 (0.59–1.32) | |
No autoimmune disease | APS event | 1.52 (1.07–2.16) | 0.94 (0.89–0.99) | 1.42 (0.93–2.16) | 0.96 (0.92.1.01) |
Thrombotic event | 1.25 (0.87–1.79) | 0.97 (0.91–1.02) | 1.46 (0.96–2.23) | 0.96 (0.91–1.01) | |
Obstetric event | 1.76 (1.08–2.87) | 0.9 (0.8–1.01) | 1.21 (0.61–2.42) | 0.98 (0.9–1.06) |
Sensitivity | Specificity | Positive LR | Negative LR | ||
---|---|---|---|---|---|
aCL M1 | IgM | 5.46 (3.5–8.2) | 94.9 (92.9–96.6) | 1.09 (0.6–1.9) | 1.00 (0.97–1.03) |
IgG | 7.94 (5.5–11.0) | 96.11 (94.3–97.5) | 2.04 (1.2–3.4) | 0.96 (0.93–0.99) | |
aβ2GPI M1 | IgM | 5.71 (3.7–8.4) | 97.08 (95.4–98.3) | 1.96 (1.1–3.6) | 0.97 (0.94–1.00) |
IgG | 8.44 (5.9–11.6) | 96.92 (95.2–98.1) | 2.74 (1.6–4.7) | 0.94 (0.91–0.98) | |
aCL M2 | IgM | 7.44 (5.1–10.5) | 95.5 (93.5–96.9) | 1.64 (1.0–2.7) | 0.97 (0.94–1.00) |
IgG | 7.69 (5.3–10.7) | 96.11 (94.3–97.5) | 1.98 (1.2–3.3) | 0.96 (0.93–0.99) | |
aβ2GPI M2 | IgM | 6.70 (4.5–9.6) | 94.81 (92.8–96.4) | 1.29 (0.8–2.1) | 0.98 (0.95–1.02) |
IgG | 6.95 (4.7–9.9) | 95.3 (93.3–96.8) | 1.48 (0.9–2.5) | 0.98 (0.95–1.01) |
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Cabrera-Marante, O.; Garcinuño, S.; Pleguezuelo, D.E.; Gil-Etayo, F.J.; Tenica, I.; Rodríguez de Frías, E.; Zafra, D.; Castro, N.; Paz-Artal, E.; Serrano, A.; et al. Quantification of Antiphospholipid Antibodies: The Importance of Using an Appropriate Methodology for Each Clinical Profile. Int. J. Mol. Sci. 2023, 24, 17373. https://doi.org/10.3390/ijms242417373
Cabrera-Marante O, Garcinuño S, Pleguezuelo DE, Gil-Etayo FJ, Tenica I, Rodríguez de Frías E, Zafra D, Castro N, Paz-Artal E, Serrano A, et al. Quantification of Antiphospholipid Antibodies: The Importance of Using an Appropriate Methodology for Each Clinical Profile. International Journal of Molecular Sciences. 2023; 24(24):17373. https://doi.org/10.3390/ijms242417373
Chicago/Turabian StyleCabrera-Marante, Oscar, Sara Garcinuño, Daniel Enrique Pleguezuelo, Francisco J. Gil-Etayo, Iulian Tenica, Edgard Rodríguez de Frías, Denis Zafra, Nerea Castro, Estela Paz-Artal, Antonio Serrano, and et al. 2023. "Quantification of Antiphospholipid Antibodies: The Importance of Using an Appropriate Methodology for Each Clinical Profile" International Journal of Molecular Sciences 24, no. 24: 17373. https://doi.org/10.3390/ijms242417373
APA StyleCabrera-Marante, O., Garcinuño, S., Pleguezuelo, D. E., Gil-Etayo, F. J., Tenica, I., Rodríguez de Frías, E., Zafra, D., Castro, N., Paz-Artal, E., Serrano, A., & Serrano, M. (2023). Quantification of Antiphospholipid Antibodies: The Importance of Using an Appropriate Methodology for Each Clinical Profile. International Journal of Molecular Sciences, 24(24), 17373. https://doi.org/10.3390/ijms242417373