Distribution characteristics of elevated serum immunoglobulin G4 (IgG4) and its relationship with IgG4-related disease

Objective: To elucidate the distribution characteristics of elevated serum immunoglobulin G(4) (IgG(4)) and its relationship with immunoglobulin G(4)-related disease (IgG(4)-RD). Methods: In total, 14 522 unique patients who were tested for serum IgG(4) over a 4.5 year period were enrolled. Demographic and serological characteristics of all patients, and the range of diseases and serological characteristics of patients with elevated serum IgG(4), were retrospectively analysed. Organ involvement in IgG(4)-RD patients and the utility of serum immunoglobulin for distinguishing IgG(4)-RD from non-IgG(4)-RD were also investigated. Results: Elevated serum IgG(4) (> 1.4 g/L) was observed in 1793/14 522 patients (12.3%) and primarily appeared in middle-aged and elderly men. Only 7.3% of patients with elevated serum IgG(4) met the diagnostic criteria for IgG(4)-RD. Elevated serum IgG(4) was also found in over 30 types of non-IgG(4)-RD. Serum IgG(4) levels were higher in IgG(4)-RD patients with multiple-organ involvement and were positively correlated with the number of affected organs. The diagnostic utility of serum IgG(4) for IgG(4)-RD was higher than that of the IgG(4)/IgG ratio and serum IgG. The optimal serum IgG(4) cut-off value for diagnosing IgG(4)-RD was 2.06 g/L, with a sensitivity of 95.6% and specificity of 94.7%. Conclusions: Elevated serum IgG(4) may be present in multiple non-IgG(4)-RD conditions. However, a high serum IgG(4) concentration is of great value for IgG(4)-RD diagnosis, and there appears to be a positive relationship between serum IgG(4) levels and organ involvement in patients with IgG(4)-RD. Examining the IgG(4)/IgG ratio and serum IgG does not improve the ability of IgG(4)-RD diagnosis.