IgG4 is Elevated in Eosinophilic Esophagitis but Not in Gastroesophageal Reflux Disease Patients

Abstract

Background: For eosinophilic esophagitis (EoE) recently an association with immunoglobulin (Ig)G4 rather than IgE has been reported. Gastroesophageal reflux disease (GERD) is the most important differential diagnosis of EoE. We compared esophageal IgG4 plasma cell infiltration and serum IgG4 levels of EoE patients (before and after budesonide therapy) with GERD patients. Methods: Prospectively collected serum samples of 17 EoE patients before and after 8 weeks of therapy with budesonide (1 mg BID) were analyzed for total and antigen-specific IgG4 and IgE levels. Also, immunohistochemical analysis of total and IgG4-positive plasma cells was performed on esophageal biopsies of these patients. In total, 14 GERD patients without histologic proof of eosinophilic infiltration were taken as a control group. Results: Total IgG4 serum levels in EoE patients were significantly higher than in GERD patients (121.0 vs. 71.2 mg/dL; P=0.038) and decreased under budesonide therapy (121.0 vs. 104.2 mg/dL; P=0.019). IgE levels did not differ significantly between all groups. In EoE patients also a high number of esophageal IgG4-positive plasma cells was detected and significantly reduced under therapy (29.1 vs. 0.1 IgG4-positive cells; P<0.001). In GERD patients no relevant esophageal plasma cell infiltration could be seen. Conclusions: In EoE patients elevated systemic IgG4 serum levels compared with GERD patients can be seen and decrease under topical steroid therapy. Also, local IgG4 plasma cells expression is high in EoE, but not in GERD patients and normalize under therapy. These findings are further proof for a possible association of EoE with IgG4.

Distinguishing gastroesophageal reflux disease and eosinophilic esophagitis in adults: The role of esophageal mucosal immunoglobulin G4

“…14 Thus, EoE is hypothesized to be associated with IgG4 and not related to IgG4. 14 We observed that IgG4 staining was able to distinguish between EoE and GERD with a moderate sensitivity of 77% and a high specificity of 93%. This is similar to a study that showed a sensitivity and specificity of 88% and 100%, respectively.…”

“…5,6 Our results suggest that IgG4 staining can be used as an adjunct to help differentiate between EoE and GERD as previously proposed. 14 This is the first study to our knowledge that has shown positive IgG4 staining in the GERD cohort (7% [2/30]). These two patients have been confirmed, on repeat examination of their medical records, to not meet criteria for a diagnosis of EoE.…”

“…Although we confirm that IgG4 stain is significantly more prevalent in EoE than GERD, the specificity is not 100% and is consistent with most previous studies. [11][12][13][14][15][16] In the current study, less than 10% of GERD patients had a positive IgG4 stain, and up to a quarter of EoE patients had a negative IgG4 stain. Overall, our study suggests that the use of IgG4 stain has a positive predictive value of 92% for distinguishing EoE from GERD, which can be valuable in the clinical assessment of undifferentiated presentation.…”

“…15 Serum IgG4 levels and local IgG4 plasma cells expression were found to be elevated in EoE compared to GERD and reduced with topical steroid therapy, suggesting that IgG4 may be a marker of disease activity. 14 It is important to distinguish between EoE and GERD as their pathogenesis, natural history, monitoring, and treatment differ. 5 This can be challenging as many of their clinical and histological features overlap.…”

Eosinophilic esophagitis: Current concepts in diagnosis and treatment

“…EoE has not been shown to be influenced by immunoglobulin E (IgE)[25]; however, an increase in IgG4 has been found in tissue samples, and IgG4 specific to some SFED food allergens has been found in serum samples[26,27], which supports the theory that EoE is truly an IgG4-mediated disease. In clinical practice, immunostaining for IgG4 in esophageal biopsies has not been effective in diagnosing EoE, as it has a low sensitivity of 48%[28].…”