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Myofibroblast and pro-fibrotic cytokines in fibrosis of IgG4-related disease (IgG4-RD) patients from South Asia: preliminary data

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Abstract

Introduction

Fibrosis is a typical pathological characteristic in IgG4-RD patients and often irreversible. There exists a lack of suitable markers for detection of earlier onset of fibrosis in various organs in IgG4-RD patients. Hence, this study aims at analysing ambispectively the myofibroblasts and the pro-fibrotic cytokines, IFN gamma and IL-33 involved in IgG4-RD associated fibrosis in South Asian patients.

Method

Archived biopsy samples of definite/probable/possible cases of IgG4-RD, classified according to diagnostic criteria, taken from patients who attended the OPD and IPD of our tertiary care centre during January 2015–January 2020 were chosen for this study. The paraffin sections were examined qualitatively for fibrosis and the excessive collagen deposition by Hematoxylin & Eosin and Masson’s Trichrome staining. Also, the presence of alpha-Smooth muscle actin (α-SMA) expressing myofibroblasts and the involvement of pro-fibrotic cytokines (IFN-gamma, IL-33) were assessed by Immunohistochemistry and scored semi-quantitatively (+mild, ++moderate, +++ severe). Serum IL-33 levels were analysed by indirect Elisa (R & D Systems).

Results

Myofibroblasts were present in 10/12 biopsy samples, in moderate levels in 4 (33%) and very high levels (+++) in 3 (25%) of the patients. IFN-gamma was expressed at low levels in 6 (50%) and absent in 6 (50%). All patients showed IL-33 expression with very high levels in tissue (6, 50%), as well as in serum samples.

Conclusion

The findings of this study reinforce the role of myofibroblasts and profibrotic cytokines like IL-33 in fibrosis of Ig4-RD patients, pointing to their potential as earlier predictive markers of onset and extent of fibrosis.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to acknowledge Dr. Amey Baitule and Dr. Reshma Kurien, Dept. Pathology, CMC Vellore for helping in screening of IgG4-RD patients. We are thankful to Mrs. Priya and Mr. Karthi for technical support to this work.

Funding

This work is funded by the internal fluid grant (No. 12562) of Christian Medical College, Vellore.

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Authors and Affiliations

  1. Department of Clinical Immunology & Rheumatology, Christian Medical College, Vellore, Tamil Nadu, 632004, India

    Josna Joseph, V. Prabhu & John Mathew

  2. Department of Pathology, Christian Medical College, Vellore, India

    Meera Thomas & Thomas Alex Kodiatte

  3. Department of Biostatistics, Christian Medical College, Vellore, India

    Reka Karuppusami

  4. Head and Neck Surgery Unit I, Christian Medical College, Vellore, India

    Rajiv Michael

  5. Department of Hepatopancreaticobiliary (HPB) Surgery, Christian Medical College, Vellore, India

    Manbha L. Rymbai

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  1. Josna Joseph
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [Josna Joseph, Prabhu V, Meera Thomas, Reka Karuppusami, John Mathew). The first draft of the manuscript was written by [Josna Joseph] and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to John Mathew.

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Joseph, J., Prabhu, V., Thomas, M. et al. Myofibroblast and pro-fibrotic cytokines in fibrosis of IgG4-related disease (IgG4-RD) patients from South Asia: preliminary data. Clin Rheumatol 43, 1103–1110 (2024). https://doi.org/10.1007/s10067-023-06861-9

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