Castleman Disease Diagnostics and Treatment Strategies

Castleman disease is a heterogeneous group of rare lymphoproliferative disorders encompassing unicentric and multicentric forms. Diagnostics integrate clinical evaluation, imaging, histopathology and molecular biomarkers to distinguish between hyaline-vascular, plasma-cell and mixed histological variants and to identify idiopathic multicentric Castleman disease (iMCD) subtypes. Technological advances in CT and MRI have refined non-invasive detection of characteristic lymphadenopathy, vascular proliferation and organomegaly while serological assays for cytokines, chemokines and acute-phase reactants support early recognition of inflammatory flares. The emergence of circulating biomarkers such as CXCL13 and interferon γ-induced protein 10 has facilitated stratification of disease activity, particularly in TAFRO syndrome—a constellation of thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly. Treatment strategies have evolved from corticosteroids and cytotoxic chemotherapy to targeted agents including anti-interleukin-6 monoclonal antibodies, JAK inhibitors and mTOR inhibitors. Long-term safety data for IL-6 blockade confirm durable disease control, whereas preclinical models of T-cell and cytokine pathways herald novel immunoregulatory approaches. Multidisciplinary protocols that combine molecular diagnostics and precision therapies are enhancing outcomes and offering globally applicable models for management of this complex condition.

Research from Nature Portfolio

Recent studies have elucidated the pathogenic roles of peripheral helper T cells and chemokine signalling in iMCD. A humanised xenograft model demonstrated that expansion of Tph cells drives lethal inflammation via elevated CXCL13, and that neutralisation of CXCL13 mitigates tissue pathology and improves survival. This work positions chemokine blockade as a potential diagnostic marker and therapeutic strategy. Complementary investigations have characterised the cytokine milieu in TAFRO-type iMCD, revealing markedly raised levels of IP-10 during disease flares alongside elevations of IL-10, IL-23 and vascular endothelial growth factor-A. These findings suggest that circulating IP-10 may serve as a biomarker for disease onset and progression and provide a rationale for cytokine-targeted interventions.

Castleman Disease Diagnostics and Treatment Strategies publication trend

The graph below shows the total number of articles in castleman disease diagnostics and treatment strategies across all publications each year (not limited to Nature Index journals).

Technical terms

Idiopathic multicentric Castleman disease (iMCD): A subtype of Castleman disease without HHV-8 association, marked by systemic inflammatory symptoms and multiple lymph node involvement.

TAFRO syndrome: A clinical variant of iMCD characterised by thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly.

CXCL13: A B-cell chemoattractant chemokine implicated in follicular helper T-cell recruitment and lymphoid tissue organisation, elevated in iMCD.

Interferon γ-induced protein 10 (IP-10): A chemokine involved in T-cell trafficking and inflammation, associated with disease flares in TAFRO syndrome.

mTOR (mechanistic target of rapamycin): A serine-threonine kinase regulating cell growth and immune responses, abnormally activated in TAFRO-type iMCD.

References

1. Peripheral helper-T-cell-derived CXCL13 is a crucial pathogenic factor in idiopathic multicentric Castleman disease. Nature Communications (2023).
2. Elevated serum interferon γ-induced protein 10 kDa is associated with TAFRO syndrome. Scientific Reports (2017).
3. Exploring the Clinical Diversity of Castleman Disease and TAFRO Syndrome: A Japanese Multicenter Study on Lymph Node Distribution Patterns. American Journal of Hematology (2025).
4. Imaging and clinical features of Castleman Disease. Cancer Imaging (2019).
5. Type I IFN response associated with mTOR activation in the TAFRO subtype of idiopathic multicentric Castleman disease. JCI Insight (2020).
6. A phase 2, open-label, multicenter study of the long-term safety of siltuximab (an anti-interleukin-6 monoclonal antibody) in patients with multicentric Castleman disease. Oncotarget (2015).