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IL-6 expression helps distinguish Castleman's disease from IgG4-related disease in the lung
Yasuhiro Kinugawa1, Takeshi Uehara2, Mai Iwaya1
1Department of Laboratory Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
Background:
It is difficult to distinguish between multicentric Castleman's disease (MCD) and IgG4-related lung disease (IgG4-LD), an IgG4-related disease (IgG4-RD) in the lung.
Methods:
We focused on IL-6, which is elevated in MCD, to distinguish between MCD and IgG4-LD by RNAscope, a highly sensitive RNA in situ method. Six cases of MCD and four cases of IgG4-LD were selected.
Results:
In all cases of MCD and IgG4-LD, 10 or more IgG4-positive cells were found in one high-power field. All MCD cases were inconsistent with the pathological IgG4-related comprehensive diagnostic criteria, but 2 of 6 cases had an IgG4/IgG ratio greater than 40%. In all IgG4-LD cases, histological features were consistent with the pathological IgG4-RD comprehensive diagnostic criteria. IL-6 expression was observed in all MCD and IgG4-LD cases except for one IgG4-LD biopsy. IL-6-expressing cells were mainly identified in the stroma. Sites of IL-6 expression were not characteristic and were sparse. IL-6 expression tended to be higher in MCD compared with IgG4-LD. A positive correlation was found between the IL-6 H-score and serum IL-6 level.
Conclusion:
Differences in IL-6 expression may help distinguish between MCD and IgG4-LD. In addition, the presence of high IL-6 levels may help elucidate the pathological mechanisms of IgG4-LD.
Insights
Distinguishing multicentric Castleman's disease (MCD) from IgG4-related lung disease (IgG4-LD) can be challenging. Interleukin-6 (IL-6) expression levels may aid in differentiating these conditions, offering insights into IgG4-related disease mechanisms.
Area of Science:
- Pulmonology
- Immunology
- Pathology
Background:
- Differentiating multicentric Castleman's disease (MCD) from IgG4-related lung disease (IgG4-LD) presents diagnostic challenges.
- Both conditions can affect the lungs and share some overlapping features.
Purpose of the Study:
- To investigate the utility of Interleukin-6 (IL-6) expression in distinguishing between MCD and IgG4-LD.
- To explore the role of IL-6 in the potential pathogenesis of IgG4-related lung disease.
Main Methods:
- Analyzed six cases of MCD and four cases of IgG4-LD.
- Utilized RNAscope, a sensitive RNA in situ hybridization method, to assess IL-6 expression.
- Evaluated IgG4-positive cell counts and IgG4/IgG ratios.
Main Results:
- While both conditions showed IgG4-positive cells, MCD cases did not fully meet IgG4-related disease criteria.
- IL-6 expression was detected in most cases of both MCD and IgG4-LD, primarily in stromal cells.
- IL-6 expression levels tended to be higher in MCD compared to IgG4-LD, with a positive correlation between IL-6 H-score and serum IL-6 levels.
Conclusions:
- Differential IL-6 expression patterns may serve as a biomarker to distinguish between MCD and IgG4-LD.
- Elevated IL-6 levels might contribute to the understanding of the pathological mechanisms underlying IgG4-LD.

