Diagnostic Performance of Serum IgG4 Levels in Patients With IgG4-Related Disease

Abstract

The aim of this study is to study the clinical features and diagnostic performance of IgG4 in Chinese populations with IgG4-related diseases (IgG4-RDs).The medical records of 2901 adult subjects who underwent serum IgG4 level tests conducted between December 2007 and May 2014 were reviewed.Serum concentrations of IgG4 were measured in 2901 cases, including 161 (5.6%) patients with IgG4-RD and 2740 (94.4%) patients without IgG4-RD (non-IgG4-RD group). The mean age of the IgG4-RD patients was 58.4 ± 16.1 years (range: 21–87), and 48 (29.8%) were women. The mean serum IgG4 level was significantly much higher in IgG4-RD patients than in non-IgG4-RD (1062.6 vs 104.3 mg/dL, P < 0.001) participants. For IgG4 >135 mg/dL, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio (LR)+, and LR− were 86%, 77%, 18%, 99%, 3.70, and 0.19, respectively. When the upper limit of normal was doubled for an IgG4 >270 mg/dL, the corresponding data were 75%, 94%, 43%, 98%, 12.79, and 0.26, respectively. For IgG4 >405 mg/dL (tripling the upper limit of normal), the corresponding data were 62%, 98%, 68%, 98%, 37.00, and 0.39, respectively. When calculated according to the manufacturer's package insert cutoff (>201 mg/dL) for the diagnosis of IgG4-RD, the corresponding sensitivity, specificity, PPV, NPV, LR+, and LR− were 80%, 89%, 29%, 99%, 7.00, and 0.23, respectively. For IgG4 >402 mg/dL (>2× the upper limit of the normal range), the corresponding data were 62%, 98%, 68%, 98%, 36.21, and 0.39, respectively. For IgG4 >603 mg/dL (>3× the upper limit of the normal range), the corresponding data were 50%, 99%, 84%, 97%, 90.77 and 0.51, respectively. The optimal cutoff value of serum IgG4 (measured by nephelometry using a Siemens BN ProSpec instrument and Siemens reagent) for the diagnosis of IgG4-RD was 248 mg/dL, the sensitivity and specificity were 77.6% and 92.8%, respectively.The present study demonstrated that 2 or 3 times the upper limit of the manufacturer's reference range of the IgG4 level was a useful marker for the diagnosis of various types of IgG4-RD and the optimal cutoff level was 248 mg/dL.

iMAP™ imaging of tumorous lesions surrounding the coronary arteries in a patient with an elevated serum level of immunoglobulin G4

“…In our case, repeated measures of serum IgG4 level showed a largest value of four times the upper limit of normal. Although the upper limit of the serum IgG4 level was rather different from that in Yu et al study, an IgG4 level of 427 mg/dL was greater than the 405 mg/dl cutoff value cited in the study by Yu et al where a sensitivity, specificity, positive predictive value, and negative predictive value were 62, 98, 68, and 98 %, respectively [37]. We excluded the possibility of malignant lymphoma or other malignant tumors using PET/CT, gallium scintigraphy, and whole-body CT, as well as soluble IL2R measurement.…”

“…Thus, the diagnosis of suspected IgG4-RD was limited to a possibility at best, and was performed by checking for elevated levels of serum IgG4 and the presence of multiple periarterial lesions, as indicated in the comprehensive clinical diagnostic criteria for IgG4-RD [16,36]. Recently, Yu et al reported that a level of two or three times the upper limit of the manufacturer's reference range for serum IgG4 is a marker of various types of IgG4-RD [37]. The optimal cutoff value of serum IgG4 for the diagnosis of IgG4-RD was 248 mg/day, and the sensitivity and specificity were 77.6 and 92.8 %, respectively.…”

Immunoglobulin G4-Related Disease and the Lung

“…3,21,[61][62][63] Serum IgG4 level has been reported to be elevated in 50% to 95% of patients with active IgG4-RD. 8,61,63,64 Conversely, only 10% to 20% of patients with an elevated serum IgG4 level in clinical practice have IgG4-RD. 62,65,66 Thus, an elevated serum IgG4 level is supportive of the diagnosis of IgG4-RD but not necessary nor sufficient.…”

Orbital IgG4-associated diseases

“…Additional IgG4-RDs have been identified, based on systemic fibroinflammatory disease characterized by the presence of lesions with lymphoplasmacytic infiltrate with high levels of IgG4-positive plasma cells. In addition,a correlation between higher levels of IgG4 and good response to therapy with corticoids has been observed [2,[6][7][8][9][11][12][13][14][15][16][17][18]. Hamano et al, [19,20] observed not only elevated levels of IgG4 in autoimmune pancreatitis, but also found characteristic histopathological manifestations accompanying retroperitoneal fibrosis.…”

“…Polyclonal increase of IgG4 levels as a result of common food and animal-derived allergens supports the idea of potential damage of regulatory mechanisms of immune system [33]. It is important to note that IgG4-RD can be diagnosed even without elevated levels of IgG4 [18,34]. Despite clear progress, dependable diagnostic criteria remain to be found [21,22].…”