Clinical and Pathological Predictors of Relapse in IgG4-Related Disease

Ji Zongfei; Chen Lingli; Sun Ying; Ma Lingying; Zhang Lijuan; Liu Dongmei; Dai Xiaomin; Hou Yingyong; Chen Huiyong; Ma Lili; Jiang Lindi


Arthritis Res Ther. 2022;24(106) 

In This Article

Abstract and Introduction


Objectives: In IgG4-related disease, the relationship between pathological findings and relapse has not been well established. This study aimed to identify the clinical and pathological predictors of disease relapse in IgG4-RD.

Methods: Patients with newly diagnosed IgG4-RD (n = 71) were enrolled between January 2011 and April 2020; all cases were pathologically confirmed. The clinical and pathological features were recorded in a database at baseline and each follow-up visit. Patients were followed up at least once a month via outpatient clinic examinations and telephone calls. Univariate and multivariate Cox regression analyses and receiver operating curve (ROC) analysis were used to identify the predictors of disease relapse and to assess their predictive value.

Results: Over a median follow-up of 26 (range, 6–123) months, 3/71 (4.2%) patients died. Of the remaining 68 patients, 47 (69.1%) patients had achieved clinical remission and 21 (30.9%) had suffered relapse at the last follow-up. The independent predictors of relapse were IgG4 ≥ 6.5 g/L (HR = 2.84, 95% CI: 1.11–7.23), IgG ≥ 20.8 g/L (HR = 4.11, 95% CI: 1.53–11.06), IgG4-RD responder index (RI) ≥ 9 (HR = 3.82, 95% CI: 1.28–11.37), and severe IgG4+ plasma cell infiltration (HR = 6.32, 95% CI: 1.79–22.41). A prognostic score developed using three of the identified predictors (IgG ≥ 20.8 g/L, IgG4-RD RI ≥ 9, and severe IgG4+ plasma cell infiltration) showed good value for predicting impending relapse (AUC, 0.806).

Conclusions: In patients with IgG4-RD, IgG4 ≥ 6.5 g/L, IgG ≥ 20.8 g/L, IgG4-RD responder index (RI) ≥ 9, and severe IgG4+ plasma cell infiltration are predictors of relapse.


IgG4-related disease (IgG4-RD) is a newly recognized systemic autoimmune disease that can involve the pancreatobiliary tract, retroperitoneum/aorta, head and neck region, and salivary glands.[1] The etiology is unknown. Single or multiple organomegaly may be present and, therefore, the disease often has to be differentiated from tumor.[1] Histopathological examination is one of the major criteria for the diagnosis of IgG4-RD according to the 2019 ACR/EULAR classification criteria, the characteristic findings being IgG4+ plasma cell infiltration, storiform fibrosis, and obliterative phlebitis.[2,3]

Relapse is common in IgG4-RD, occurring in 24–54% of patients after reduction of glucocorticoid dose.[4–9] The 2-year relapse rates are 23.0–41.4%.[9,10] Patients with relapse present with reappearance of organomegaly and organ dysfunction (e.g., renal insufficiency, liver cirrhosis, intestinal obstruction). Previous studies have identified high serum IgG4 level, multiple organ involvement, high IgG4-RD responder index (RI) score, high serum IgE, and high eosinophil count at baseline as predictors of long-term relapse.[11,12] Increase in memory B cell count after corticosteroid treatment and persistence of T-follicular helper cells after rituximab are also reported to be associated with relapse.[13,14] In addition, our previous study[8] found serum TNF-α level and IL-2R to be independent predictors of relapse.

Although the pathological diagnostic criteria for IgG4-RD have been established,[15–21] the pathological features associated with disease relapse are not known. The aim of this study was to investigate the relationship between pathological manifestations and disease relapse in IgG4-RD and to identify the independent predictors of disease relapse.