Cytotoxic Molecules as Potential Biomarkers for Active and Inactive Systemic Lupus Erythematosus
<b>Objectives</b>: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by persistent inflammation. Reliable biomarkers for predicting disease reactivation are lacking. This study aimed to investigate serum cytokines and cytotoxic molecules in both the inacti...
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2025-06-01
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| author | Paola Santana-Sánchez Astrid Asminda Ramírez-Pérez Paolo Alberti-Minutti Julián A. Gajón Laura C. Bonifaz Norberto Sánchez-Escobar María Victoria Legorreta-Haquet Luis Chávez-Sánchez Adriana Karina Chávez-Rueda |
| author_facet | Paola Santana-Sánchez Astrid Asminda Ramírez-Pérez Paolo Alberti-Minutti Julián A. Gajón Laura C. Bonifaz Norberto Sánchez-Escobar María Victoria Legorreta-Haquet Luis Chávez-Sánchez Adriana Karina Chávez-Rueda |
| author_sort | Paola Santana-Sánchez |
| collection | DOAJ |
| description | <b>Objectives</b>: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by persistent inflammation. Reliable biomarkers for predicting disease reactivation are lacking. This study aimed to investigate serum cytokines and cytotoxic molecules in both the inactive (iSLE) and active (aSLE) phases to identify potential predictors of disease activity. <b>Methods</b>: Fifty-five SLE patients were classified as having iSLE (<i>n</i> = 36) or aSLE (<i>n</i> = 19) on the basis of clinical parameters and the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Serum levels of cytokines, cytotoxic molecules, and CD8<sup>+</sup> cells were analyzed through flow cytometry and principal component analysis (PCA). Additionally, seventeen healthy donors (HDs) served as a control group. <b>Results:</b> Serum perforin (median: 2219 pg/mL; <i>p</i> = 0.0020) and granulysin (median: 1347 pg/mL; <i>p</i> = 0.010) levels were significantly higher in patients with aSLE than in patients with iSLE. In contrast, sFas levels were elevated in both SLE groups compared with those in the HD group. Moreover, increased perforin and granulysin levels were correlated with increased SLEDAI-2K scores, and the proportion of cytotoxic cells (CD8<sup>+</sup>granzyme-B<sup>+</sup>perforin<sup>+</sup> cells) was correlated with disease activity. <b>Conclusions</b>: The increased levels of cytotoxic molecules and the high CD8<sup>+</sup> cell proportions suggest that integrating these parameters with traditional biomarkers could enhance disease monitoring and management. |
| format | Article |
| id | doaj-art-67f4fffe05b1411c9c16cd04e1fd66b4 |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-06-01 |
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| series | Biomedicines |
| spelling | doaj-art-67f4fffe05b1411c9c16cd04e1fd66b42025-08-20T04:00:54ZengMDPI AGBiomedicines2227-90592025-06-01137155910.3390/biomedicines13071559Cytotoxic Molecules as Potential Biomarkers for Active and Inactive Systemic Lupus ErythematosusPaola Santana-Sánchez0Astrid Asminda Ramírez-Pérez1Paolo Alberti-Minutti2Julián A. Gajón3Laura C. Bonifaz4Norberto Sánchez-Escobar5María Victoria Legorreta-Haquet6Luis Chávez-Sánchez7Adriana Karina Chávez-Rueda8Unidad de Investigación Médica en Inmunología, Unidad Médica de Alta Especialidad (UMAE) Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, MexicoServicio de Reumatología, Unidad Médica de Alta Especialidad (UMAE) Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, MexicoServicio de Medicina Interna, Unidad Médica de Alta Especialidad (UMAE) Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, MexicoPosgrado en Ciencias Bioquímicas, Universidad Nacional Autonoma de México, Mexico City 04510, MexicoUnidad de Investigación Médica en Inmunoquímica, Unidad Médica de Alta Especialidad (UMAE) Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, MexicoUnidad de Investigación Médica en Inmunología, Unidad Médica de Alta Especialidad (UMAE) Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, MexicoUnidad de Investigación Médica en Inmunología, Unidad Médica de Alta Especialidad (UMAE) Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, MexicoUnidad de Investigación Médica en Inmunología, Unidad Médica de Alta Especialidad (UMAE) Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, MexicoUnidad de Investigación Médica en Inmunología, Unidad Médica de Alta Especialidad (UMAE) Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico<b>Objectives</b>: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by persistent inflammation. Reliable biomarkers for predicting disease reactivation are lacking. This study aimed to investigate serum cytokines and cytotoxic molecules in both the inactive (iSLE) and active (aSLE) phases to identify potential predictors of disease activity. <b>Methods</b>: Fifty-five SLE patients were classified as having iSLE (<i>n</i> = 36) or aSLE (<i>n</i> = 19) on the basis of clinical parameters and the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Serum levels of cytokines, cytotoxic molecules, and CD8<sup>+</sup> cells were analyzed through flow cytometry and principal component analysis (PCA). Additionally, seventeen healthy donors (HDs) served as a control group. <b>Results:</b> Serum perforin (median: 2219 pg/mL; <i>p</i> = 0.0020) and granulysin (median: 1347 pg/mL; <i>p</i> = 0.010) levels were significantly higher in patients with aSLE than in patients with iSLE. In contrast, sFas levels were elevated in both SLE groups compared with those in the HD group. Moreover, increased perforin and granulysin levels were correlated with increased SLEDAI-2K scores, and the proportion of cytotoxic cells (CD8<sup>+</sup>granzyme-B<sup>+</sup>perforin<sup>+</sup> cells) was correlated with disease activity. <b>Conclusions</b>: The increased levels of cytotoxic molecules and the high CD8<sup>+</sup> cell proportions suggest that integrating these parameters with traditional biomarkers could enhance disease monitoring and management.https://www.mdpi.com/2227-9059/13/7/1559systemic lupus erythematosusSLEDAI 2-Kperforingranulysingranzyme-BCD8<sup>+</sup> T cell |
| spellingShingle | Paola Santana-Sánchez Astrid Asminda Ramírez-Pérez Paolo Alberti-Minutti Julián A. Gajón Laura C. Bonifaz Norberto Sánchez-Escobar María Victoria Legorreta-Haquet Luis Chávez-Sánchez Adriana Karina Chávez-Rueda Cytotoxic Molecules as Potential Biomarkers for Active and Inactive Systemic Lupus Erythematosus Biomedicines systemic lupus erythematosus SLEDAI 2-K perforin granulysin granzyme-B CD8<sup>+</sup> T cell |
| title | Cytotoxic Molecules as Potential Biomarkers for Active and Inactive Systemic Lupus Erythematosus |
| title_full | Cytotoxic Molecules as Potential Biomarkers for Active and Inactive Systemic Lupus Erythematosus |
| title_fullStr | Cytotoxic Molecules as Potential Biomarkers for Active and Inactive Systemic Lupus Erythematosus |
| title_full_unstemmed | Cytotoxic Molecules as Potential Biomarkers for Active and Inactive Systemic Lupus Erythematosus |
| title_short | Cytotoxic Molecules as Potential Biomarkers for Active and Inactive Systemic Lupus Erythematosus |
| title_sort | cytotoxic molecules as potential biomarkers for active and inactive systemic lupus erythematosus |
| topic | systemic lupus erythematosus SLEDAI 2-K perforin granulysin granzyme-B CD8<sup>+</sup> T cell |
| url | https://www.mdpi.com/2227-9059/13/7/1559 |
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