CXCL13 Expression in the Lymph Node and Kidney of a Patient with Idiopathic Multicentric Castleman Disease with TAFRO Syndrome

Idiopathic multicentric Castleman disease with TAFRO syndrome (iMCD-TAFRO) is an inflammatory disorder caused by a cytokine storm involving interleukin-6 (IL-6) and is often associated with kidney injury. Recent proteomic analyses have identified CXCL13 (a chemokine for inducing migration of B cells) as one of the most upregulated serum proteins in iMCD. CXCL13 is highly expressed in iMCD lymph nodes. However, the mechanisms underlying kidney injury in iMCD and the contribution of CXCL13 remain unclear.

We report a case of iMCD-TAFRO complicated by kidney injury, in which CXCL13 was highly expressed not only in the lymph node but also in the kidney. The patient showed marked improvement of kidney function and proteinuria following treatment with corticosteroids and tocilizumab, an anti–IL-6 receptor antibody.

A 57-year-old man presented with 1 month of progressive anasarca, oliguria, fatigue, and dyspnea. Nephrotic syndrome was suspected, and he was admitted to the nephrology department for further evaluation. Laboratory data showed a urine protein-creatinine ratio of 5.31 g/gCr, microscopic hematuria (50–99 RBC/HPF), serum albumin 2.9 g/dL, and serum creatinine 1.2 mg/dL, consistent with nephrotic syndrome with hematuria and kidney dysfunction. Additional testing revealed thrombocytopenia (platelet count 94 ×103/μL) and elevated inflammatory markers (CRP 10.04 mg/dL and IL-6 37.2 pg/mL). Computed tomography demonstrated splenomegaly, cervical lymphadenopathy, and pleural and ascitic effusions. Kidney biopsy showed endothelial cell swelling in all glomeruli. Bone marrow biopsy revealed increased reticulin fibers and megakaryocytic proliferation. Cervical lymph node biopsy demonstrated blurring of follicular architecture with indistinct germinal centers and prominent vascular proliferation. CXCL13 immunostaining showed positive staining not only in the germinal centers of the lymph node but also in a subset of glomerular cells and extensively within tubular epithelial cells in the kidney. Taken together, these findings established a diagnosis of iMCD-TAFRO. Intravenous methylprednisolone (500 mg/day for 3 days) followed by oral prednisolone (60 mg/day, approximately 1 mg/kg/day) was started on hospital day 8. Kidney function began to improve; however, proteinuria (approximately 1–2 g/g creatinine) and low-grade inflammation (CRP 1–2 mg/dL) persisted. Tocilizumab 560 mg (8 mg/kg every 2 weeks) was initiated on hospital day 25. Clinical symptoms resolved, inflammatory markers normalized, kidney function returned to baseline (serum creatinine 0.94 mg/dL), and the patient was discharged on hospital day 58. Proteinuria improved to 0.66 g/gCr two months after the initiation of tocilizumab.

Combination therapy with glucocorticoids and tocilizumab achieved clinical remission in iMCD-TAFRO with kidney involvement. The presence of CXCL13-positive cells in glomeruli and tubules suggests that intrarenal CXCL13 expression may contribute to iMCD–associated kidney injury.

Figure 1. Kidney and lymph node biopsy findings: (a) PAM staining shows endothelial injury. (b) CXCL13 is positive in the glomerulus and tubules of the kidney. (c) CXCL13 is positive in the germinal centers of the lymph node.