Diagnostic utility of serum IgG4 level in IgG4-related diseases: a comprehensive systematic review and meta-analysis

Background Despite many studies suggesting an association between serum IgG4 and IgG4-related diseases (IgG4-RD), the evidence of the utility of serum IgG4 titres in differentiating between IgG4-RD and non-IgG4-RD remains uncertain. Methods The primary analysis was based on published studies. Data were pooled by means of a random-effect model, and sensitivity, specificity, positive likelihood ratios (LR+), negative likelihood ratios (LR–), diagnostic ORs (DOR) and summary receiver operating characteristic curve (SROC) were calculated. Subgroup analyses were performed based on the racial/ethnic distribution of these studies. Results A total of 27 studies with 1691 (8.6%) IgG4-RD cases and 17 944 non-IgG4-RD subjects were included. Moreover, 1462 (86.5%) of the 1691 IgG4-RD patients had elevated serum IgG4 levels whereas 10.5% (1,882 of 17,944) of the non-IgG4-RD subjects had elevated serum IgG4 levels. The pooled sensitivity of serum IgG4 was 86% (85%–88%), specificity was 90% (89%–90%), LR+ was 9.19 (7.16–11.78), LR– was 0.17 (0.12–0.24), and the DOR was 60.8 (40.9–90.4), respectively. The area under the SROC curve for the differential diagnosis between IgG4-RD and non-IgG4-RD was 0.95 (0.94–0.97). Ethnic subgroup analyses revealed different findings with respect to DOR for Asian (103.8; 95% CI 63.3 to 170.2), and Caucasian (25.7; 95% CI 17.6 to 37.5) populations. Conclusions Overall, elevated serum IgG4 levels were associated with IgG4-RD. The results revealed a moderate-to-high sensitivity (86%, 85%–88%) and high specificity (90%, 89%–90%). Subgroup analyses in serum IgG4 diagnostic performance revealed differences among Asian and Caucasian populations.