Expresión linfocitaria y niveles de IL-2 en el síndrome nefrótico corticorresistente por glomeruloesclerosis focal y segmentaria: implicaciones en la respuesta a los inhibidores de calcineurina.

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Title:	Expresión linfocitaria y niveles de IL-2 en el síndrome nefrótico corticorresistente por glomeruloesclerosis focal y segmentaria: implicaciones en la respuesta a los inhibidores de calcineurina.
Alternate Title:	Lymphocytic expression and IL-2 levels in calcineurin inhibitor-resistant nephrotic syndrome due to focal segmental glomerulosclerosis: implications for calcineurin inhibitor response.
Authors:	Planella-Cornudella, Maria^1,2 mplanellac.lleida.ics@gencat.cat, Roca-Saladrigues, Neus³, Lopez-Baez, Victor⁴, Jatem-Escalante, Elias^2,5, Sole-Mir, Eduard^1,2, Gomez-Arbones, Xavier^2,6, Madrid-Aris, Alvaro⁴, Segarra-Medrano, Alfons^2,5
Source:	Nefrologia. Jan2026, Vol. 46 Issue 1, p1-8. 9p.
Subjects:	NEPHROTIC syndrome, FOCAL segmental glomerulosclerosis, CALCINEURIN, LYMPHOCYTE transformation, INTERLEUKIN-2, BIOMARKERS, T cells
Abstract (English):	Background and objective: Calcineurin inhibitors (CNI) are the first-line treatment for steroid-resistant nephrotic syndrome (SRNS) due to focal segmental glomerulosclerosis (FSGS), though response rates vary. This study analyzed lymphocyte activation through IL-2 receptor expression on T lymphocytes and serum IL-2Ra (soluble CD25) levels in these patients to evaluate their relationship with response to CNI therapy. Materials and methods: A multicenter case-control study was conducted with 39 patients with steroid-resistant FSGS, diagnosed via renal biopsy, and 23 healthy controls. Clinical, biochemical, and immunological variables were assessed. Soluble CD25 levels were measured using ELISA, and lymphocyte activation was analyzed by flow cytometry. Treatment criteria and response evaluation followed KDIGO guidelines. Diagnostic performance was assessed using ROC curves for soluble CD25. Results: The 48.7% of patients responded to CNI treatment. Soluble CD25 levels and IL-2 expression on CD3 T lymphocytes were significantly associated with CNI response (P<.01): responders had higher CD25 levels (477 ± 84.47 pg/ml) compared to non-responders (290.28 ± 85.98 pg/ml). Responders showed a significant reduction in soluble CD25 (-35.8%) and CD3-IL2+ cells after remission, alongside increases in CD8 DR+ cells and regulatory T cells. ROC analysis identified a soluble CD25 cutoff of 324 pg/ml, with 94% sensitivity and 75% specificity for predicting response to CNI. Conclusions: Elevated soluble CD25 levels and T cell activation were associated with better CNI response. Soluble CD25 could be a predictive biomarker to identify patients with higher likelihood of response, optimizing therapeutic decisions and avoiding unnecessary treatments in steroid-resistant FSGS. [ABSTRACT FROM AUTHOR]
Abstract (Spanish):	Antecedentes y objetivo: Ante un síndrome nefrótico (SN) resistente a corticoesteroides por una glomeruloesclerosis focal y segmentaria (GFS), los inhibidores de la calcineurina (ICN) constituyen la primera línea de tratamiento, aunque la respuesta es variable. Este estudio analizóla activación linfocitaria en estos pacientes mediante la expresión de receptores de IL-2 en linfocitos y los niveles séricos de IL-2Ra (CD25 soluble) para evaluar su relación con la respuesta al tratamiento con los ICN. Material y métodos: Se realizóun estudio caso-control multicéntrico en 39 pacientes con SN por GFS resistente a corticoides, diagnosticada por biopsia renal, y 23 controles sanos. Se evaluaron variables clínicas, bioquímicas e inmunológicas. Los niveles de CD25 soluble se midieron mediante ELISA y la activación linfocitaria mediante citometría de flujo. Tanto los criterios de tratamiento como la evaluación de la respuesta a los ICN se definieron según los criterios de las guías KDIGO. Los datos se analizaron mediante curvas ROC para determinar el rendimiento diagnóstico de CD25 soluble. Resultados: Un 48,7% de los pacientes respondióal tratamiento con los ICN. Los niveles de CD25 soluble y la expresión de IL-2 en linfocitos CD3 se asociaron significativamente con la respuesta a los ICN (p < 0,01) con valores de CD25 soluble 477 ± 84,47 (respondedores) vs. 290,28 ± 85,98 pg/ml (no respondedores). Tras la remisión, los pacientes sensibles a los ICN mostraron una reducción significativa de CD25 soluble (-35,8%), linfocitos CD3 y CD3-IL2+, junto con un incremento en CD8 DR+ y células T reguladoras. El análisis ROC identificóun punto de corte de 324 pg/ml de CD25 soluble, con una sensibilidad del 94% y una especificidad del 75% para predecir la respuesta a los ICN. Conclusiones: En nuestro estudio, los niveles elevados de CD25 soluble y la activación linfocitaria T se asoció con una mejor respuesta al tratamiento con los ICN. La medición de CD25 soluble podría integrarse como un biomarcador predictivo útil para identificar de manera temprana a los pacientes con mayor probabilidad de respuesta, optimizando así las decisiones terapéuticas y evitando tratamientos innecesarios en la GFS resistente a corticoides. Este estudio presenta ciertas limitaciones, como el tamaño reducido de la muestra y la ausencia de validación externa. [ABSTRACT FROM AUTHOR]
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Database:	MedicLatina

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Abstract:	Background and objective: Calcineurin inhibitors (CNI) are the first-line treatment for steroid-resistant nephrotic syndrome (SRNS) due to focal segmental glomerulosclerosis (FSGS), though response rates vary. This study analyzed lymphocyte activation through IL-2 receptor expression on T lymphocytes and serum IL-2Ra (soluble CD25) levels in these patients to evaluate their relationship with response to CNI therapy. Materials and methods: A multicenter case-control study was conducted with 39 patients with steroid-resistant FSGS, diagnosed via renal biopsy, and 23 healthy controls. Clinical, biochemical, and immunological variables were assessed. Soluble CD25 levels were measured using ELISA, and lymphocyte activation was analyzed by flow cytometry. Treatment criteria and response evaluation followed KDIGO guidelines. Diagnostic performance was assessed using ROC curves for soluble CD25. Results: The 48.7% of patients responded to CNI treatment. Soluble CD25 levels and IL-2 expression on CD3 T lymphocytes were significantly associated with CNI response (P<.01): responders had higher CD25 levels (477 ± 84.47 pg/ml) compared to non-responders (290.28 ± 85.98 pg/ml). Responders showed a significant reduction in soluble CD25 (-35.8%) and CD3-IL2+ cells after remission, alongside increases in CD8 DR+ cells and regulatory T cells. ROC analysis identified a soluble CD25 cutoff of 324 pg/ml, with 94% sensitivity and 75% specificity for predicting response to CNI. Conclusions: Elevated soluble CD25 levels and T cell activation were associated with better CNI response. Soluble CD25 could be a predictive biomarker to identify patients with higher likelihood of response, optimizing therapeutic decisions and avoiding unnecessary treatments in steroid-resistant FSGS. [ABSTRACT FROM AUTHOR]
ISSN:	02116995
DOI:	10.1016/j.nefro.2025.501402