A Comparative Study on Serum Immunoglobulin and Tumor Marker Levels in the Patients with Autoimmune Pancreatitis and Pancreatobiliary Malignancies

Hwan Yoon; Myung-Hwan Kim; Sung Hyun Won; Do Hyun Park; Sang Soo Lee; Dong Wan Seo; Sung Koo Lee

doi:10.4166/kjg.2013.61.6.327

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Yoon, Kim, Won, Park, Lee, Seo, and Lee: A Comparative Study on Serum Immunoglobulin and Tumor Marker Levels in the Patients with Autoimmune Pancreatitis and Pancreatobiliary Malignancies

Original Article

Korean J Gastroenterol 2013;61(6):327-332.

Published online: 4 October 2013

DOI: https://doi.org/10.4166/kjg.2013.61.6.327

A Comparative Study on Serum Immunoglobulin and Tumor Marker Levels in the Patients with Autoimmune Pancreatitis and Pancreatobiliary Malignancies

Hwan Yoon, Myung-Hwan Kim, Sung Hyun Won, Do Hyun Park, Sang Soo Lee, Dong Wan Seo, Sung Koo Lee

Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Correspondence to: Myung-Hwan Kim, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa- gu, Seoul 138-736, Korea. Tel: +82-2-3010-3183, Fax: +82-2-3010-3180, E-mail: mhkim@amc.seoul.kr

Received 13 November 20129 May 2013 Accepted 10 May 2013

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background/Aims

Autoimmune pancreatitis (AIP) often occurs with obstructive jaundice in old age in cases of weight loss, mimicking pancreatobiliary cancer. This study aimed to determine the sensitivity and specificity serum IgG, IgG4 and CEA, CA 19–9 levels for the diagnosis of AIP and their ability to distinguish AIP from pancreatobiliary cancer.

Methods

The level of serums IgG, IgG4 and CEA, CA 19–9 were measured in 413 patients including 125 with AIP, 201 with pancreatic cancer, and 87 with cholangiocarcinoma.

Results

Among AIP patients, 43.2% (54/125) showed elevated IgG levels (≥1,800 mg/dL) and 52% (65/125) showed elevated IgG4 levels (≥135 mg/dL). Sensitivity and specificity of elevated serum IgG for diagnosis AIP were 43% and 88% respectively, and 52% and 97%, respectively for elevated serum IgG4. When the cut-off value of serum IgG4 was raised to 270 mg/dL (twice the upper limit of normal), the specificity improved to 100%. About 25% of the AIP patients showed an increased level of CA 19–9 at ＞37 U/mL and about 12.2% of them showed an increased level of CA 19–9 at ＞100 U/mL. On the contrary, only 1.8% of the AIP patients showed an increased level of CEA at ＞6.0 ng/mL.

Conclusions

To avoid unnecessary surgeries resulting from a misdiagnosed pancreatobiliary cancer as opposed to AIP, it is necessary to consider both serum immunoglobulin and tumor marker. In particular, because high level of IgG4 (≥270 mg/dL) and CA19–9 (＞100 U/mL) are relatively rare in pancreatobiliary cancer and AIP, respectively, they will be helpful in differential diagnosis.

Keywords: Autoimmune pancreatitis, Immunoglobulins, Immunoglobulin G4, Carcinoembryonic antigen, CA 19–9

References

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Fig. 1.

Distribution of serum IgG level. There was a significant difference in the serum IgG levels among the 3 groups (Kruskal- Wallis after logarithmic transformation, p＜0.001). AIP, autoimmune pancreatitis.

Fig. 2.

Distribution of serum IgG4 level. There was a significant difference in the serum IgG4 levels among the 3 groups (Kruskal- Wallis after logarithmic transformation, p＜0.001). AIP, autoimmune pancreatitis.

Fig. 3.

Receiver operating characteristics (ROC) curve of serum IgG and IgG4 in patients with autoimmune pancreatitis (AIP). The sensitivity and specificity of IgG4 at 133 mg/dL was 52% and 97%, respectively, in the differentiation of AIP from pancreatobiliary malignancies (area under the ROC curve [AUC], 0.77). The sensitivity and specificity of IgG at 1,335 mg/dL was 78.4% and 55.6%, respectively (AUC, 0.73).

Table 1.

Korean Criteria for Autoimmune Pancreatitis (by Korean Pancreatobiliary Association, 2007)

Definite diagnosis: Criterion I together with any of criterion II to IV Criterion I. Imaging (both required)

1. Imaging (CT or MRI) of pancreatic parenchyma; Diffusely/segmentally/focally enlarged gland, occasionally with mass and/or hypoattenuation rim

2. Imaging (ERCP or MRCP) of pancreaticobiliary ducts; Diffuse/segmental/focal pancreatic ductal narrowing, often with the stensosis of bile duct

Criterion II. Serology (one required)

1. Elevated level of serum IgG or IgG4

2. Detected autoantibodies

Criterion III. Histopathology of pancreatic/extrapancreatic lesions (one required)

1. Lymphoplasmacytic infiltration & fibrosis, often with obliterative phlebitis

2. Presence of abundant (＞10 cells/high power field) IgG4-positive plasma cells

Criterion IV. Response to steroids

1. Resolution/marked improvement of pancreatic/extrapancreatic lesion with steroid therapy

Probable Diagnosis: Criterion V or VI Criterion V.

1. Unexplained pancreatic disease but only with characteristic pancreatic histology

Criterion VI. (Both required)

1. Other organ involvement and/or serologic abnormalities

2. Various atypical pancreatic imaging suggesting chronic pancreatitis with negative workup for known etiologies

Table 2.

Comparision of Patients with AIP and Pancreatobiliary Malignancies

Group	AIP (n=125)	Pancreatic cancer (n=201)	Cholangiocarcinoma (n=87)	p-value
Age (yr)	56.4±15.1	61.2±11.1	63.4±11.5	0.003
Male to female ratio	5.3:1	1.5:1	1.4:1	0.004
IgG level (mg/dL)	1,970.4±1,011.9 (781–6,990)	1,306.0±325.4 (780–2,650)	1,536.3±482.8 (839–3,850)	＜0.001
IgG4 level (mg/dL)	274.1±420.6 (2–3,200)	42.1±37.1 (1–253)	43.9±40.0 (1–153)	＜0.001
CEA level (ng/mL)	1.94±1.56 (0.1–32.0)	16.9±83.5 (0.4–771.0)	29.6±213.3 (0.5–1,970.0)	＜0.001
CA 19–9 level (mg/dL)	49.1±112.7 (0.6–783)	957.1±3,997.0 (0.6–51,600.0)	2,004.1±482.8 (0.6–50,600.0)	) ＜0.001

Values are presented as mean±SD, median (range), or number only.

AIP, autoimmune pancreatitis.

Table 3.

Sensitivity and Specificity of IgG4 in the Diagnosis of AIP

Immunoglobulin (mg/dL)	AIP (n=125)	PC (n=201)	CCC (n=87)	Sensitivity (%)	Specificity (%)
IgG≥1,800	54/125	15/201	19/87	43.2	88.2
	(43.2)	(7.5)	(21.8)
IgG4≥135	65/125	6/201	2/87	52.0	97.2
	(52.0)	(3.0)	(2.3)
IgG4≥270	43/125	0/201	0/87	34.4	100
	(34.4)	(0)	(0)

Values are presented as n (%) or percent only.

AIP, autoimmune pancreatitis; PC, pancreatic cancer; CCC, cholangiocarcinoma.

Table 4.

The Elevation of Serum IgG and IgG4 in Patients with Autoimmune Pancreatitis (n=125)

	IgG4 elevation (＞135 mg/dL)
	Yes	No
IgG elevation Yes	34 (27.2)	20 (16)
(≥1,800 mg/dL) No	31 (24.8)	40 (32)

Values are presented as n (%).

Table 5.

Serum CEA and CA 19–9 Levels of AIP and Pancreatobiliary Malignancies

	AIP (n=125)	PC (n=201)	CCC (n=87)	p-value
CEA elevation
＞6 ng/mL	2/112	39/201	21/87	0.004
	(1.8)	(19.4)	(24.1)
CA 19–9 elevation
＞37 mg/dL	29/115	142/201	57/87	＜0.001
	(25.2)	(70.6)	(65.5)
＞100 mg/dL	14/115	105/201	39/87	＜0.001
	(12.2)	(52.2)	(44.8)

Values are presented as n (%).

AIP, autoimmune pancreatitis; PC, pancreatic cancer; CCC, cholangiocarcinoma.

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