Background Sclerosing pancreatitis is a unique form of pancreatitisthat is characterized by irregular narrowing of the main pancreaticduct, lymphoplasmacytic inflammation of the pancreas, and hypergammaglobulinemiaand that responds to glucocorticoid treatment. Preliminary studiessuggested that serum IgG4 concentrations are elevated in thisdisease but not in other diseases of the pancreas or biliarytract.
Methods We measured serum IgG4 concentrations using single radialimmunodiffusion and an enzyme-linked immunosorbent assay in20 patients with sclerosing pancreatitis, 20 age- and sex-matchednormal subjects, and 154 patients with pancreatic cancer, ordinarychronic pancreatitis, primary biliary cirrhosis, primary sclerosingcholangitis, or Sjögren's syndrome. Serum concentrationsof immune complexes and the IgG4 subclass of immune complexeswere determined by means of an enzyme-linked immunosorbent assaywith monoclonal rheumatoid factor.
Results The median serum IgG4 concentration in the patientswith sclerosing pancreatitis was 663 mg per deciliter (5th and95th percentiles, 136 and 1150), as compared with 51 mg perdeciliter (5th and 95th percentiles, 15 and 128) in normal subjects(P<0.001). The serum IgG4 concentrations in the other groupsof patients were similar to those in the normal subjects. Inpatients with sclerosing pancreatitis, serum concentrationsof immune complexes and the IgG4 subclass of immune complexeswere significantly higher before glucocorticoid therapy thanafter four weeks of such therapy. Glucocorticoid therapy inducedclinical remissions and significantly decreased serum concentrationsof IgG4, immune complexes, and the IgG4 subclass of immune complexes.
Conclusions Patients with sclerosing pancreatitis have highserum IgG4 concentrations, providing a useful means of distinguishingthis disorder from other diseases of the pancreas or biliarytract.
Source Information
From the Second Department of Internal Medicine (H.H., S.K., A.H., H.U., N.F., T.A., K.K.) and the Departments of Laboratory Medicine (M.F.), Obstetrics and Gynecology (T.N.), Organ Generation (T.N.), and Anatomy (K.N.), Shinshu University School of Medicine, Matsumoto, Japan; and the Department of Anatomy, Fujita Health University School of Medicine, Toyoake, Japan (N.U.).
Address reprint requests to Dr. Kawa at the Second Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan, or at skawapc{at}hsp.md.shinshu-u.ac.jp.
LAW, R., BRONNER, M., VOGT, D., STEVENS, T.
(2009). Autoimmune pancreatitis: A mimic of pancreatic cancer. Cleveland Clinic Journal of Medicine
76: 607-615
[Abstract][Full Text]
Kurosawa, S., Akiyama, N., Ohwada, A., Warabi, M., Suenaga, M., Kojima, M., Tomiyama, J.
(2009). Idiopathic Plasmacytic Lymphadenopathy with Polyclonal Hypergammaglobulinemia Accompanied with Cutaneous Involvement and Renal Dysfunction. Jpn J Clin Oncol
39: 682-685
[Abstract][Full Text]
Patel, K. C., Flowers, R., Bhagat, R.
(2009). A DECADE WITH ATYPICAL LYMPHOPLASMACYTIC DISEASE PROCESS: A CASE WITH HYPER-IGG4 DISEASE OF THE LUNG. Chest Meeting
136: 18S-18S
[Abstract]
Masaki, Y, Dong, L, Kurose, N, Kitagawa, K, Morikawa, Y, Yamamoto, M, Takahashi, H, Shinomura, Y, Imai, K, Saeki, T, Azumi, A, Nakada, S, Sugiyama, E, Matsui, S, Origuchi, T, Nishiyama, S, Nishimori, I, Nojima, T, Yamada, K, Kawano, M, Zen, Y, Kaneko, M, Miyazaki, K, Tsubota, K, Eguchi, K, Tomoda, K, Sawaki, T, Kawanami, T, Tanaka, M, Fukushima, T, Sugai, S, Umehara, H
(2009). Proposal for a new clinical entity, IgG4-positive multiorgan lymphoproliferative syndrome: analysis of 64 cases of IgG4-related disorders. Ann Rheum Dis
68: 1310-1315
[Abstract][Full Text]
Stone, J. H., Caruso, P. A., Deshpande, V.
(2009). Case 24-2009 -- A 26-Year-Old Woman with Painful Swelling of the Neck. NEJM
361: 511-518
[Full Text]
Mise, N., Tomizawa, Y., Fujii, A., Yamaguchi, Y., Sugimoto, T.
(2009). A case of tubulointerstitial nephritis in IgG4-related systemic disease with markedly enlarged kidneys. NDT Plus
2: 233-235
[Abstract][Full Text]
Nagai, K., Hosaka, H., Takahashi, Y., Kubo, S., Nakamura, N., Andou, K.
(2009). A case of IgG4-related sclerosing disease complicated by sclerosing cholangitis, retroperitoneal fibrosis and orbital pseudotumour. BMJ Case Reports
2009: bcr0220091590-bcr0220091590
[Abstract][Full Text]
Inoue, D., Zen, Y., Abo, H., Gabata, T., Demachi, H., Kobayashi, T., Yoshikawa, J., Miyayama, S., Yasui, M., Nakanuma, Y., Matsui, O.
(2009). Immunoglobulin G4-related Lung Disease: CT Findings with Pathologic Correlations. Radiology
251: 260-270
[Abstract][Full Text]
Endo, T., Takizawa, S., Tanaka, S., Takahashi, M., Fujii, H., Kamisawa, T., Kobayashi, T.
(2009). Amylase {alpha}-2A Autoantibodies: Novel Marker of Autoimmune Pancreatitis and Fulminant Type 1 Diabetes. Diabetes
58: 732-737
[Abstract][Full Text]
Ryu, J. H.
(2009). Unusual and Uncommon Pulmonary Disorders. ACCP Pulmonary Med Brd Rev
25: 479-486
[Full Text]
Hirschfield, G. M., Al-Harthi, N., Heathcote, E. J.
(2009). Review: Current status of therapy in autoimmune liver disease. Therapeutic Advances in Gastroenterology
2: 11-28
[Abstract]
Shakov, R., DePasquale, J. R., Elfarra, H., Spira, R. S.
(2009). Autoimmune Pancreatitis: Case Series and Review of the Literature.. Annals of Clinical & Laboratory Science
39: 167-175
[Abstract][Full Text]
Sahani, D. V., Sainani, N. I., Deshpande, V., Shaikh, M. S., Frinkelberg, D. L., Fernandez-del Castillo, C.
(2009). Autoimmune Pancreatitis: Disease Evolution, Staging, Response Assessment, and CT Features That Predict Response to Corticosteroid Therapy. Radiology
250: 118-129
[Abstract][Full Text]
Moon, S-H, Kim, M-H, Park, D H, Hwang, C Y, Park, S J, Lee, S S, Seo, D W, Lee, S K
(2008). Is a 2-week steroid trial after initial negative investigation for malignancy useful in differentiating autoimmune pancreatitis from pancreatic cancer? A prospective outcome study. Gut
57: 1704-1712
[Abstract][Full Text]
Leise, M. D., Jacobson, K. M., Chari, S. T.
(2008). 75-Year-Old Man With Abdominal Pain and Weight Loss. Mayo Clin Proc.
83: 1161-1164
[Full Text]
Chen, T S, Montgomery, E A
(2008). Are tumefactive lesions classified as sclerosing mesenteritis a subset of IgG4-related sclerosing disorders?. J. Clin. Pathol.
61: 1093-1097
[Abstract][Full Text]
Kojima, M., Miyawaki, S., Takada, S., Kashiwabara, K., Igarashi, T., Nakamura, S.
(2008). Lymphoplasmacytic Infiltrate of Regional Lymph Nodes in Kuttner's Tumor (Chronic Sclerosing Sialadenitis): A Report of 3 Cases. INT J SURG PATHOL
16: 263-268
[Abstract]
Kawamoto, S., Siegelman, S. S., Hruban, R. H., Fishman, E. K.
(2008). Lymphoplasmacytic Sclerosing Pancreatitis (Autoimmune Pancreatitis): Evaluation with Multidetector CT. RadioGraphics
28: 157-170
[Abstract][Full Text]
Hirano, K., Tada, M., Isayama, H., Yagioka, H., Sasaki, T., Kogure, H., Nakai, Y., Sasahira, N., Tsujino, T., Yoshida, H., Kawabe, T., Omata, M.
(2007). Long-term prognosis of autoimmune pancreatitis with and without corticosteroid treatment. Gut
56: 1719-1724
[Abstract][Full Text]
Umemura, T, Zen, Y, Hamano, H, Ichijo, T, Kawa, S, Nakanuma, Y, Kiyosawa, K
(2007). IgG4 associated autoimmune hepatitis: a differential diagnosis for classical autoimmune hepatitis. Gut
56: 1471-1472
[Full Text]
Kobayashi, S, Yoshida, M, Kitahara, T, Abe, Y, Tsuchida, A, Nojima, Y
(2007). Autoimmune pancreatitis as the initial presentation of systemic lupus erythematosus. Lupus
16: 133-136
[Abstract]
Tsushima, K., Kubo, K., Kawa, S., Hamano, H.
(2007). IgG4-associated multifocal systemic fibrosis presenting with fever of unknown origin. QJM
100: 141-142
[Full Text]
Aleksic, T., Baumann, B., Wagner, M., Adler, G., Wirth, T., Weber, C. K
(2007). Cellular immune reaction in the pancreas is induced by constitutively active I{kappa}B kinase-2. Gut
56: 227-236
[Abstract][Full Text]
Umemura, T, Ota, M, Hamano, H, Katsuyama, Y, Kiyosawa, K, Kawa, S
(2006). Genetic association of Fc receptor-like 3 polymorphisms with autoimmune pancreatitis in Japanese patients.. Gut
55: 1367-1368
[Full Text]
Rudmik, L., Trpkov, K., Nash, C., Kinnear, S., Falck, V., Dushinski, J., Dixon, E.
(2006). Autoimmune pancreatitis associated with renal lesions mimicking metastatic tumours.. CMAJ
175: 367-369
[Abstract][Full Text]
Sutton, R
(2005). Autoimmune pancreatitis--also a Western disease. Gut
54: 581-583
[Full Text]
Aparisi, L, Farre, A, Gomez-Cambronero, L, Martinez, J, De Las Heras, G, Corts, J, Navarro, S, Mora, J, Lopez-Hoyos, M, Sabater, L, Ferrandez, A, Bautista, D, Perez-Mateo, M, Mery, S, Sastre, J
(2005). Antibodies to carbonic anhydrase and IgG4 levels in idiopathic chronic pancreatitis: relevance for diagnosis of autoimmune pancreatitis. Gut
54: 703-709
[Abstract][Full Text]
Yamamoto, M., Harada, S., Ohara, M., Suzuki, C., Naishiro, Y., Yamamoto, H., Takahashi, H., Imai, K.
(2005). Clinical and pathological differences between Mikulicz's disease and Sjogren's syndrome. Rheumatology (Oxford)
44: 227-234
[Abstract][Full Text]
van der Vliet, H. J.J., Perenboom, R. M.
(2004). Multiple Pseudotumors in IgG4-Associated Multifocal Systemic Fibrosis. ANN INTERN MED
141: 896-897
[Full Text]
Kawamoto, S., Siegelman, S. S., Hruban, R. H., Fishman, E. K.
(2004). Lymphoplasmacytic Sclerosing Pancreatitis with Obstructive Jaundice: CT and Pathology Features. Am. J. Roentgenol.
183: 915-921
[Abstract][Full Text]
Duvic, C., Desrame, J., Leveque, C., Nedelec, G.
(2004). Retroperitoneal fibrosis, sclerosing pancreatitis and bronchiolitis obliterans with organizing pneumonia. Nephrol Dial Transplant
19: 2397-2399
[Full Text]
Messiou, C, Chalmers, A G
(2004). Imaging in acute pancreatitis. Imaging
16: 314-322
[Abstract][Full Text]
Pallais, J. C., Kifor, O., Chen, Y.-B., Slovik, D., Brown, E. M.
(2004). Acquired Hypocalciuric Hypercalcemia Due to Autoantibodies against the Calcium-Sensing Receptor. NEJM
351: 362-369
[Full Text]
Taniguchi, T, Ko, M, Seko, S, Nishida, O, Inoue, F, Kobayashi, H, Saiga, T, Okamoto, M, Fukuse, T, Kamisawa, T, Funata, N, Okamoto, A
(2004). Interstitial pneumonia associated with autoimmune pancreatitis * Author's reply. Gut
53: 770-771
[Full Text]
Fernandez-del Castillo, C. F., Sahani, D. V., Lauwers, G. Y.
(2003). Case 27-2003 - A 36-Year-Old Man with Recurrent Epigastric Pain and Elevated Amylase Levels. NEJM
349: 893-901
[Full Text]
Kamisawa, T, Funata, N, Hayashi, Y, Tsuruta, K, Okamoto, A, Amemiya, K, Egawa, N, Nakajima, H
(2003). Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis. Gut
52: 683-687
[Abstract][Full Text]
Okazaki, K, Chiba, T
(2002). Autoimmune related pancreatitis. Gut
51: 1-4
[Abstract][Full Text]
Chen, R. Y.M., Adams, D. B.
(2002). IgG4 Levels in Non-Japanese Patients with Autoimmune Sclerosing Pancreatitis. NEJM
346: 1919-1919
[Full Text]
Aithal, G. P., Breslin, N. P., Gumustop, B., Kawa, S., Hamano, H., Kiyosawa, K.
(2001). High Serum IgG4 Concentrations in Patients with Sclerosing Pancreatitis. NEJM
345: 147-148
[Full Text]
(2001). Sclerosing Pancreatitis: A Unique Disease Associated with High IgG4 Concentrations. JWatch Gastroenterology
2001: 6-6
[Full Text]