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Exploring the role of insulin-like growth factor binding protein-1 in identifying idiopathic multicentric Castleman's
Remi Sumiyoshi1, Tomohiro Koga2, Shoichi Fukui2
1Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Clincal Research Center, Nagasaki University Hospital, Nagasaki, Japan.
Objective:
To determine the molecular differences between iMCD-thrombocytopenia, anasarca, fevers, reticulin myelofibrosis, organomegaly (TAFRO), and iMCD-not otherwise specified (NOS).
Methods:
CD4-positive T cells were isolated from two iMCD-TAFRO and two iMCD-NOS patients for RNA sequencing comparison. Serum proteins of two iMCD-TAFRO and four iMCD-NOS patients were comprehensively analyzed to identify pathogenesis-associated proteins. IGFBP-1 protein, extracted from serum analysis, was compared to healthy controls, iMCD, systemic lupus erythematosus, and rheumatoid arthritis patients.
Results:
RNA sequencing of CD4-positive T cells revealed enhanced mTOR-related signaling in iMCD-TAFRO compared to iMCD-NOS. Comprehensive serum analysis found IGFBP-1 linked to iMCD pathogenesis, significantly higher in iMCD-TAFRO. This protein may be elevated in patients with iMCD caused by an enhanced mTOR pathway.
Conclusion:
The mTOR pathway is suggested to be activated in iMCD-TAFRO compared to iMCD-NOS, which may elevate the protein IGFBP-1. This protein may be a biomarker to distinguish iMCD-TAFRO from iMCD-NOS.
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