Evaluation of serum IgG4 levels as a screening tool for IgG4-related disease: Data from a retrospective study

IgG4-related disease (IgG4-RD) is a systemic, immune-mediated, fibro-inflammatory condition with an uncertain etiology and pathophysiology that can affect multiple organs, presenting common clinical, radiological, and serological features. Although the disease is associated with IgG4, serum levels are not elevated in all patients and have also been described in other diseases. The aim of this study is to evaluate the clinical utility of elevated serum IgG4 as a screening marker in the suspicion of IgG4-related disease.

A retrospective single-center study was conducted, analysing serological IgG4 test requests from electronic medical records of patients ordered by various hospital departments from January 2010 to June 2023. Only those with elevated IgG4 levels were included in the analysis. Additionally, demographic data and final diagnoses, including those with IgG4-RD, were collected.

A total of 2288 test requests were reviewed, of which 247 showed elevated IgG4 levels (181 after excluding duplicates). Among the patients with elevated IgG4, only 11 met the criteria for IgG4-RD based on the 2011 Umehara-Okazaki classification and its 2020 update. However, only 6 patients (3.31%) met the more recent 2019 ACR/EULAR classification criteria for IgG4-RD. In the remaining patients with elevated IgG4, the most common diagnoses were respiratory diseases, such as COPD and asthma, followed by systemic autoimmune diseases, primarily SLE, RA, and EGPA. Elevated IgG4 levels were also observed in malignant neoplasms, predominantly lung and hematologic cancers.

Our study highlights that elevated IgG4 levels are not exclusive to IgG4-RD and can also be observed in various respiratory diseases (e.g., COPD), autoimmune diseases (e.g., SLE and RA), and neoplasms (e.g., lung cancer).