Background/Purpose: Hyper-immunoglobulin G4 (IgG4) has been reported in various conditions including autoimmune disease, gastrointestinal disorders, lymphoproliferative/granulomatous diseases and solid tumors. IgG4-related disease is an immune-mediated fibroinflammatory condition with multiorgan involvement. This diagnosis relies on significant IgG4+plasma cell infiltrate in tissues in the proper clinical setting. Systemic autoinflammatory disease(SAID) is rare, and its potential association with hyper-IgG4 has not been reported. This study was to report the first case series of patients.

Methods: A retrospective study of a case series of adult patients with SAIDs and elevated serum IgG4 level between 2016 and April 2022 was conducted. These patients were thoroughly evaluated and managed in our Center of Autoinflammatory Disease. Systemic autoimmune diseases were excluded after extensive workups. All patients had genetic testing for periodic fever syndromes. Individual SAID was diagnosed based on the characteristic phenotype and specific genotypes.

Results: A total of 4 adult patients with SAIDs were included. The demographic, clinical, molecular and theraptic data are listed in Table 1. The mean age at disease diagnosis was 31 years and the average disease duration at diagnosis was 18 years. All patients were females. Patient 1 was diagnosed with TNF receptor associated periodic syndrome(TRAPS) along with elevated serum IgG4 level. Patient 2 was diagnosed with Yao syndrome with elevated serum IgG4 level. Cervical lymph node biopsy showed no adequate IgG4 staining. Patients 3 was diagnosed with NLRP3-AID. Due to the higher levels of serum IgG4, cervial lymph node biopsy did not support IgG4 related disease. Patient 4 was diagnosed with familial Medetranean fever(FMF) with good therapeutic response to colchicine. The patient had temporary serum IgG4 elevation. Our results showed mild to moderate elevation of serum IgG4 levels in all 4 patrients but there was insufficient evidence of IgG4-related disease. All 4 patients reported a history of food or drug allergies that could be associated with IgG4 elevation or SAIDs. All patients reported significant gastrointestinal symptoms without inflammatory bowel disease. Taken together, these data suggest that hyper-IgG4 could be an integral part of certain SAIDs rather than coexistence of both SAID and IgG4-related disease.

Conclusion: Our study is the first report to show that hyper-IgG4 can occur in SAID patients. Serum IgG4 elevation could be involved in the autoinflammatory process and may not represent a IgG4 related disease. Further study is needed with a larger sample size.

« Back to ACR Convergence 2022

ACR Meeting Abstracts - https://acrabstracts.org/abstract/hyper-igg4-in-patients-with-systemic-autoinflammatory-disease/