Work

Efficacy of JAK-inhibition in therapy-refractory full-house membranous glomerulopathy with type I interferon-pathway activation in the setting of anti-synthetase syndrome: a case report

Year: 2026

Type: article

Abstract: We report a patient with nephrotic syndrome with preserved kidney function due to membranous glomerulopathy with a full-house immunofluorescence pattern, in the setting of anti-synthetase syndrome. The glomerular disease of the patient was resistant to multiple lines of treatment including corticosteroids, anti-CD20 therapy and calcineurin inhibition, and the patient suffered from serious treatment-related morbidity and complications due to ongoing nephrosis. We found evidence of an increased type I interferon activation in the kidney tissue specimen as well as in the circulation of the patient, consistent with the pivotal role of the JAK-STAT-pathway in the pathogenesis of systemic auto-immune disease with inflammatory myositis. Using tofacitinib, we initiated JAK-inhibition resulting in complete response of his nephrotic syndrome (and extra-renal disease activity). Kidney involvement in anti-synthetase syndrome is rare and efficacy of JAK-inhibition in glomerular disease has not been reported before. Our case suggests that JAK-inhibition may be a promising treatment modality in inflammatory myositis-associated glomerular disease.

Source: Heliyon

DOI: 10.1016/j.heliyon.2026.e45635

Authors: D. Verhoeven, J.J.T.H. Roelofs, M.L. Hilhorst, A.J. Kwakernaak

Institutions: Amsterdam UMC Location University of Amsterdam, Amsterdam University Medical Centers, Amsterdam institute for Immunology and Infectious Diseases, University of Amsterdam

Language: English

Topic: Renal Diseases and Glomerulopathies

Subfield: Nephrology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,270