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

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.