Scholarlink

<p>We report a unique case of membranous nephropathy and tubulointerstitial nephritis preceding neurological manifestations of Bing-Neel syndrome, a rare variant of Waldenström macroglobulinemia. A 46-year-old man presented with nephrotic syndrome, and kidney biopsy revealed membranous nephropathy with phospholipase A2 receptor positivity and IgG4 predominance. Despite initial partial remission with corticosteroids and cyclosporine, neurological symptoms emerged alongside nephrotic syndrome relapse two years after onset. Diagnostic workup revealed serum monoclonal IgM kappa, abnormal lymphoplasmacytic cells in bone marrow and cerebrospinal fluid, and <i>MYD88</i> L265P mutation in the latter, confirming Bing-Neel syndrome. Immunostaining of the initial kidney biopsy demonstrated IgM-kappa-positive lymphoplasmacytic infiltration consistent with the monoclonal protein. After bendamustine-rituximab therapy showed partial effectiveness, tirabrutinib, a Bruton tyrosine kinase inhibitor, achieved complete remission of both renal and neurological manifestations with sustained response over three years. Immunofluorescence staining revealed increased nuclear factor (NF)-κB and STAT3 expression in infiltrating immune cells and elevated NF-κB in surrounding tubular epithelial cells, suggesting activation of these pathways downstream of the <i>MYD88</i> mutation in kidney pathology. Our findings suggest a potential contribution of Bruton's tyrosine kinase signaling to both kidney and neurological pathology in Bing-Neel syndrome, with tirabrutinib achieving clinical improvement in both organ manifestations.</p> Graphical abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Membranous nephropathy preceding Bing-Neel syndrome: successful treatment with tirabrutinib

  • 期刊论文

  • 发表日期：

    2025年9月26日

查看全文
  • Kanako Watanabe-Kusunoki,
  • Daigo Nakazawa,
  • Hiroyuki Ohigashi,
  • Takahiro Tsuji,
  • Tatsuya Atsumi

摘要

We report a unique case of membranous nephropathy and tubulointerstitial nephritis preceding neurological manifestations of Bing-Neel syndrome, a rare variant of Waldenström macroglobulinemia. A 46-year-old man presented with nephrotic syndrome, and kidney biopsy revealed membranous nephropathy with phospholipase A2 receptor positivity and IgG4 predominance. Despite initial partial remission with corticosteroids and cyclosporine, neurological symptoms emerged alongside nephrotic syndrome relapse two years after onset. Diagnostic workup revealed serum monoclonal IgM kappa, abnormal lymphoplasmacytic cells in bone marrow and cerebrospinal fluid, and MYD88 L265P mutation in the latter, confirming Bing-Neel syndrome. Immunostaining of the initial kidney biopsy demonstrated IgM-kappa-positive lymphoplasmacytic infiltration consistent with the monoclonal protein. After bendamustine-rituximab therapy showed partial effectiveness, tirabrutinib, a Bruton tyrosine kinase inhibitor, achieved complete remission of both renal and neurological manifestations with sustained response over three years. Immunofluorescence staining revealed increased nuclear factor (NF)-κB and STAT3 expression in infiltrating immune cells and elevated NF-κB in surrounding tubular epithelial cells, suggesting activation of these pathways downstream of the MYD88 mutation in kidney pathology. Our findings suggest a potential contribution of Bruton's tyrosine kinase signaling to both kidney and neurological pathology in Bing-Neel syndrome, with tirabrutinib achieving clinical improvement in both organ manifestations.

Graphical abstract