Phenotyping of IgG4-related diseases based on affected organ pattern: A multicenter cohort study using cluster analysis

Abstract

Objectives

Immunoglobulin G4-related disease (IgG4-RD) is a systemic, multiorgan disease of unknown etiology. We aimed to classify IgG4-RD by a combination pattern of affected organs and identify the clinical features, including the comorbidities of each subgroup.

Methods

Patients diagnosed with IgG4-RD between April 1996 and June 2018 were enrolled from three institutes. Hierarchical cluster analysis was performed using six frequently affected organs (lacrimal gland and/or orbit, salivary gland, lung, pancreas, kidney, and retroperitone and/or aorta). Clinical features, such as comorbidities and outcomes, were compared between clusters.

Results

In total, 108 patients enrolled in this cohort could be stratified into five distinct subgroups: group 1, lung dominant group; group 2, retroperitoneal fibrosis and/or aortitis dominant group; group 3, salivary glands limited group; group 4, Mikulicz’s disease dominant group; and group 5, autoimmune pancreatitis with systemic involvement group. There were significant between-group differences in sex (male dominant in group 1, 2, and 5), history of asthma and allergies on the respiratory tract (most frequent in group 5), and malignancy (most frequent in group 5).

Conclusion

IgG4-RD can be classified into subgroups according to the pattern of affected organs. Group 5 may have frequent complications with allergies and malignancies.

Keywords:

• Autoimmune pancreatitis
• clinical phenotypes
• cluster analysis
• IgG4-related disease
• Mikulicz disease

Acknowledgments

We thank Dr. Kiminobu Tanizawa (Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University) and Dr. Yoshinari Nakatsuka (Department of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University) for their contribution to clinical practice of the patients.

Conflict of interest

None.

Additional information

Funding

This study was supported by grants from the Practical Research Project for Rare/Intractable Diseases from Japan Agency for Medical Research and Development, AMED [No. 16ek0109051h0003], the Research Committee to establish diagnostic criteria and treatment development for systemic IgG4-related sclerosing disease, supported by the Research Program of Intractable Disease, Ministry of Health, Labor, Welfare of Japan [No. H26-Nanchi-Ippan-050 and H29-Nanchi-Ippan-058], Japan Society for the Promotion of Science [No. 17K09612] and Ms. Mieko Sonoda Memorial Research Fund for Interstitial Lung Diseases. The funders had no role in the design of the study, the collection, analysis, and interpretation of data, and writing the manuscript.