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

• Published in: Clinical rheumatology Vol. 43; no. 8; pp. 2533 - 2540
• Main Authors: Zavala-Miranda, Maria Fernanda, Sobrino-Vargas, Ana María, Hernández-Andrade, Adriana, Caballero-Malacara, Valeria, Pérez-Arias, Abril A., Márquez-Macedo, Sofía E., Nordmann-Gomes, Alberto, Navarro-Sánchez, Valeria, Juárez-Cuevas, Bernardo, Uribe-Uribe, Norma O., Mejia-Vilet, Juan M.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.08.2024; Springer Nature B.V
• Subjects: Antigens; Autoimmune diseases; Biopsy; blood serum; class; Clinical medicine; cohort studies; Creatinine; Epidermal growth factor receptors; Glomerular filtration rate; histology; Kidney diseases; kidneys; Lupus; lupus erythematosus; Lupus nephritis; Medicine; Medicine & Public Health; Membranous nephropathy; nephritis; Nephropathy; Original Article; Prognosis; Renal failure; Rheumatology; Statistical analysis; Systemic lupus erythematosus; Exostosin; Erythematosus; Prognosis; Lupus nephritis; Membranous nephropathy; Systemic lupus
• ISSN: 0770-3198; 1434-9949; 1434-9949
• DOI: 10.1007/s10067-024-07043-x

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.