Diagnostic performance of serum IgG4 level for IgG4-related disease: a meta-analysis

Abstract

An elevated serum IgG4 level is one of the most useful factors in the diagnosis of IgG4-related disease (IgG4-RD). In this study, we performed a meta-analysis of the published articles assessing the diagnostic accuracy of serum IgG4 concentrations for IgG4-RD. The databases of MEDLINE/PubMed, EMBASE and Web of Science were systematically searched for relevant studies. Sensitivities and specificities of serum IgG4 in each study were calculated, and the hierarchical summary receiver operating characteristic (HSROC) model with a random effects model were employed to obtain the individual and pooled estimates of sensitivities and specificities. In total, twenty-three studies comprising 6048 patients with IgG4-RD were included in the meta-analysis. The pooled sensitivity was 85% with a 95% confidence interval (CI) of 78–90%; the pooled specificity was 93% with a 95% CI of 90–95%. The HSROC curve for quantitative serum IgG4 lies closer to the upper left corner of the plot, and the area under the curve (AUC) was 0.95 (95% CI 0.93, 0.97), which suggested a high diagnostic accuracy of serum IgG4 for the entity of IgG4-RD. Our study suggests that serum IgG4 has high sensitivity and specificity in the diagnosis of IgG4-RD.

Mikulicz’s disease and Sjögren’s syndrome as the main autoimmune disorders involving salivary glands

“…Serum IgG4 level exhibits sensitivity ranging from 82.3% to 89.3% and a specificity of 94.6% to 95.8% [16]. Its positive predictive value in diagnosing ranges from 36% to 79% [16]. Moreover, this predictive value does not correspond with the cut-off value of the IgG4 level [17].…”

“…Eosinophilia and increased serum IgE level are reported more frequently in IgG4-related lacrimal gland enlargement and overlapping asthma-like symptoms. These findings can be explained by the enhanced Th2 cell differentiation and IL-10 production in the pathogenesis of IgG4-related lacrimal gland enlargement [16]. Thrombocytopenia rarely occurs in MD in contrast to SS [18].…”

“…The IgG4-related symptoms are a response to Th2-dependent cytokines. Serum IgG4 level exhibits sensitivity ranging from 82.3% to 89.3% and a specificity of 94.6% to 95.8% [16]. Its positive predictive value in diagnosing ranges from 36% to 79% [16].…”

Gastrointestinal and Extra-Intestinal Manifestations of IgG4–Related Disease

“…44 A meta-analysis of 23 studies comprising 6048 patients found that serum level of IgG4-RD detected IgG4-RD with a pooled sensitivity of 85% (95% CI, 78%-90%) and a pooled specificity value of 93% (95% CI, 90%-95%). 45 Limitations of such analyses, which are acknowledged in the study, include patient inclusion bias and variable methods of measurement of serum IgG4, as well their varying upper limits of normal. Use of fold-normal rather than absolute value for serum IgG4 is more appropriate until there is an agreed-upon standard for its measurement.…”

Diagnostic and treatment workup for IgG4-related disease

“…Great mimickers of IgG4-RD including pancreatic adenocarcinoma, lymphoma, and ANCA associated vasculitis can present with elevated serum IgG4 levels while biopsy confirmed IgG4-RD patients can have normal IgG4 concentrations. A meta-analysis of predominantly Caucasian and Asian patients did not reveal a specific cut off value for serum IgG4 level to diagnose IgG4-RD, but did find significantly high pooled sensitivity and specificity for serum IgG4 level testing (25). However, another study has shown specificity and positive predictive value of elevated serum IgG4 concentrations to be 60% and 34% respectively (26).…”