Clinical and pathological differences between serum immunoglobulin G4-positive and -negative type 1 autoimmune pancreatitis

Abstract

Aim: To identify clinical and pathological differences between serum immunoglobulin G4 (IgG4)-positive (SIP) and IgG4-negative (SIN) type 1 autoimmune pancreatitis (AIP) in South Korea.

Methods: AIP was diagnosed by the international consensus diagnostic criteria. The medical records and pathology were retrospectively reviewed and IgG4-positive cells were counted in a high power field (HPF). Type I AIP was defined as a high serum level of IgG4 or histological finding. SIN type 1 AIP was defined as a histological evidence of type 1 AIP and a normal serum IgG4 level. The clinical and pathological findings were compared between the two groups. The analysis was performed using Student's t test, Fischer's exact test and Mann-Whitney's U test. A P value of < 0.05 was considered statistically significant. As repeated comparison was made, P values of less than 5% (P < 0.05) were considered significant.

Results: Twenty five patients with definite type 1 AIP (19 histologically and six serologically diagnosed cases) were enrolled. The mean tissue IgG4 concentrations were significantly higher in SIP than SIN group (40 cells per HPF vs 18 cells per HPF, P = 0.02). Among eight SIN patients, the tissue IgG4 concentrations were less than 15 cells per HPF in most of cases, except one. The sensitivity of serum IgG4 was 68% (17 SIP and eight SIN AIP). Other organ involvement was more frequently associated with SIP than SIN AIP (59% vs 26%, P = 0.016). However, the relapse rate and diffuse swelling of the pancreas were not associated with serum IgG4 level. The concentrations of IgG4-positive cells per HPF were higher in SIP than SIN AIP (40 vs 18, P = 0.02).

Conclusion: The sensitivity of serum IgG4 was 68% in type 1 AIP. High serum IgG4 level was associated with other organ involvement and tissue IgG4 concentration but did not affect the relapse rate in type 1 AIP.

Keywords: Autoimmunity; Chronic pancreatitis; Immunoglobulin G4; Immunoglobulin G4-related systemic disease; Lymphoplasmacytic sclerosing pancreatitis.

Figure 1

Enrolled patients and classification of autoimmune pancreatitis. Among 37 patients with autoimmune pancreatitis (AIP), one case was type 2 AIP and 19 patients were type 1 AIP by histology. The pathological diagnosis was inconclusive in three cases among 23 tissue samples. Among 14 patients without histology, eight patients were excluded because of normal serum immunoglobulin G4 (IgG4) levels. Ultimately, 25 patients with definite type 1 AIP (19 histologically and six serologically diagnosed cases) were enrolled in this study. LPSP: Lymphoplasmacytic sclerosing pancreatitis; IDCP: Idiopathic duct-centric chronic pancreatitis.

Figure 2

Correlation between serum and tissue immunoglobulin G4 concentrations. Among eight serum immunoglobulin G4 (IgG4)-negative (SIN) patients, the tissue IgG4 concentrations were less than 15 cells per high power filed (HPF) in most of cases, except one. Among 11 serum IgG4-positive (SIP) patients, the tissue IgG4 concentrations were more than 25 cells per HPF, except one case (15 cells per HPF). There was no linear correlation between serum and tissue IgG4 concentration among the 11 SIP patients.

Figure 3

Magnetic resonance image of 61-year-old male patient with normal serum immunoglobulin G4. A: Magnetic resonance image shows slightly exophytic mass of iso-attenuation at the body of pancreas; B: Distal parenchymal atrophy and abrupt cutting of pancreatic duct with upstream ductal dilatation.

Figure 4

Histology and immunoglobulin G4 immunohistochemical staining. A: Hematoxylin and eosin staining shows typical finding of lymphoplasmacytic sclerosing pancreatitis (× 200); B: Immunoglobulin G4 (IgG4) staining shows dense infiltration of IgG4 positive cells (× 400).