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Exostosin-1/exostosin-2 expression and favorable kidney outcomes in lupus nephritis: a retrospective cohort study

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Abstract

Introduction/Objectives

The heterodimer exostosin-1/exostosin-2 (EXO-1/2) is a novel antigen observed in membranous nephropathy associated with systemic lupus erythematosus. This study aimed to evaluate the association between EXO-1/2 positivity in kidney biopsy and kidney outcomes.

Methods

The kidney biopsy tissue from 50 class 5 lupus nephritis (LN) and 55 mixed class 3/4 + 5 LN patients was stained for EXO-1/2. Baseline clinical and histological characteristics were compared between EXO-1/2 positive and EXO-1/2 negative patients. Time-to-event analyses were performed to compare rates of response to therapy, kidney flares, and progression to a 40% decline of the glomerular filtration rate (eGFR), doubling of serum creatinine, and kidney failure.

Results

Fourteen out of 50 (28%) of class 5 and 5 out of 55 (9%) of mixed class 3/4 + 5 LN stained positive for EXO-1/2. Patients with class 5 LN and EXO-1/2 positive stain were younger, with better kidney function at presentation, and lower scarring in the kidney biopsy analysis. Over a median follow-up of 100 months, patients with positive EXO-1/2 staining had significantly lower rates of progression in the full cohort. When analyzed separately in class 5 and mixed class LN subgroups, there were significantly lower rates of progression to a 40% decline of the eGFR and non-statistically significant trends for doubling of serum creatinine and kidney failure.

Conclusion

EXO-1/2 is a novel antigen detected in class 5 LN and associated with a good prognosis of kidney function. The incorporation of EXO-1/2 staining in clinical practice can potentially modify the management of LN due to its prognostic implications.

Key Points

• Exostosin-1/exostosin-2 antigen has been found in cases of membranous nephropathy associated with autoimmune diseases such as systemic lupus erythematosus.

• Exostosin-1/exostosin-2 staining in the kidney biopsy of class 5 or mixed class 3/4 + 5 lupus nephritis is associated with a good long-term prognosis of kidney function.

• The incorporation of exostosin-1/exostosin-2 staining into clinical practice can potentially modify management due to its prognostic implications.

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Data availability

The data supporting this study is available upon reasonable request to the corresponding author.

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Acknowledgements

We thank Professor Sanjeev Sethi and Brooke E. Westling from the Mayo Clinic for their aid in establishing our local exostosin-2 staining procedure.

Funding

This work was performed with local funds from the Department of Nephrology and Mineral Metabolism and the Pathology and Anatomic Pathology Departments from Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán.

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Author notes

  1. Maria Fernanda Zavala-Miranda and Ana María Sobrino-Vargas contributed equally to the development of this study.

Authors and Affiliations

  1. Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, 15 Vasco de Quiroga, Belisario Domínguez Sección XVI, Tlalpan, 14080, Mexico City, Mexico

    Maria Fernanda Zavala-Miranda, Adriana Hernández-Andrade, Abril A. Pérez-Arias, Sofía E. Márquez-Macedo, Alberto Nordmann-Gomes, Valeria Navarro-Sánchez, Bernardo Juárez-Cuevas & Juan M. Mejia-Vilet

  2. Department of Pathology and Anatomic Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

    Ana María Sobrino-Vargas, Valeria Caballero-Malacara & Norma O. Uribe-Uribe

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  1. Maria Fernanda Zavala-Miranda
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Correspondence to Juan M. Mejia-Vilet.

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Zavala-Miranda, M.F., Sobrino-Vargas, A.M., Hernández-Andrade, A. et al. Exostosin-1/exostosin-2 expression and favorable kidney outcomes in lupus nephritis: a retrospective cohort study. Clin Rheumatol (2024). https://doi.org/10.1007/s10067-024-07043-x

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