Decreased production of immunoglobulin M and A in autoimmune pancreatitis
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Abstract
Background
Autoimmune pancreatitis (AIP) is a rare type of chronic pancreatitis caused by an autoimmune abnormality. It is well known that high serum concentrations of IgG4 are helpful for making a diagnosis of AIP; however, it is unclear whether there are abnormalities in the production of other immunoglobulins in AIP.
Methods
We examined the immune condition of AIP patients before and after glucocorticoid treatment, focusing on serum levels of IgG, IgG4, IgM and IgA, and compared the results with those in other hepato-pancreatic diseases, such as autoimmune hepatitis, primary biliary cirrhosis, chronic pancreatitis and pancreatic carcinoma.
Results
IgM and IgA were decreased in patients with untreated AIP. IgM and IgG or IgG4 were negatively correlated in patients with AIP. The ratios of IgG to IgM and IgG to IgA in patients with AIP were significantly increased compared with the other diseases. The diagnostic sensitivity of IgG to IgM and IgG to IgA was 0.800 and 0.950, and the specificity of each ratio was 0.703 and 0.728, respectively, in the differentiation of AIP from the other diseases. IgM was not significantly changed after glucocorticoid treatment in the patients with AIP, while IgG, IgG4 and IgA decreased.
Conclusions
The ratios of IgG to IgM and IgG to IgA may serve as novel diagnostic markers to differentiate AIP from other hepato-pancreatic diseases. Furthermore, low concentrations of IgM and IgA may be involved in the pathogenesis of AIP.
Keywords
Autoimmune pancreatitis Immunodeficiency Immunoglobulin A Immunoglobulin G Immunoglobulin MReferences
- 1.Otsuki M. Chronic pancreatitis in Japan: epidemiology, prognosis, diagnostic criteria, and future problems. J Gastroenterol. 2003;38:315–26.CrossRefPubMedGoogle Scholar
- 2.Otsuki M. Chronic pancreatitis. The problems of diagnostic criteria. Pancreatology. 2004;4:28–41.CrossRefPubMedGoogle Scholar
- 3.Steer ML, Waxman I, Freedman S. Chronic pancreatitis. N Engl J Med. 1995;332:1482–90.CrossRefPubMedGoogle Scholar
- 4.Whitcomb DC. Mechanisms of disease: advances in understanding the mechanisms leading to chronic pancreatitis. Nat Clin Pract Gastroenterol Hepatol. 2004;1:46–52.CrossRefPubMedGoogle Scholar
- 5.Yoshida K, Toki F, Takeuchi T, Watanabe S, Shiratori K, Hayashi N. Chronic pancreatitis caused by an autoimmune abnormality. Proposal of the concept of autoimmune pancreatitis. Dig Dis Sci. 1995;40:1561–8.CrossRefPubMedGoogle Scholar
- 6.Hamano H, Kawa S, Horiuchi A, Unno H, Furuya N, Akamatsu T, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med. 2001;344:732–8.CrossRefPubMedGoogle Scholar
- 7.Kamisawa T, Funata N, Hayashi Y, Tsuruta K, Okamoto A, Amemiya K, et al. Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis. Gut. 2003;52:683–7.CrossRefPubMedGoogle Scholar
- 8.Okazaki K, Chiba T. Autoimmune related pancreatitis. Gut. 2002;51:1–4.CrossRefPubMedGoogle Scholar
- 9.Okazaki K, Uchida K, Fukui T. Recent advances in autoimmune pancreatitis: concept, diagnosis, and pathogenesis. J Gastroenterol. 2008;43:409–18.CrossRefPubMedGoogle Scholar
- 10.Okazaki K, Kawa S, Kamisawa T, Naruse S, Tanaka S, Nishimori I, et al. Clinical diagnostic criteria of autoimmune pancreatitis: revised proposal. J Gastroenterol. 2006;41:626–31.CrossRefPubMedGoogle Scholar
- 11.Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK, Cancado EL, et al. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999;31:929–38.CrossRefPubMedGoogle Scholar
- 12.Heathcote EJ. Management of primary biliary cirrhosis. The American Association for the Study of Liver Diseases practice guidelines. Hepatology. 2000;31:1005–13.CrossRefPubMedGoogle Scholar
- 13.Goldstein MF, Goldstein AL, Dunsky EH, Dvorin DJ, Belecanech GA. Shamir K Selective IgM immunodeficiency: retrospective analysis of 36 adult patients with review of the literature. Ann Allergy Asthma Immunol. 2006;97:717–30.PubMedGoogle Scholar
- 14.Chandra RK, Kaveramma B, Soothill JF. Generalised non-progressive vaccinia associated with IgM deficiency. Lancet. 1969;1:687–9.CrossRefPubMedGoogle Scholar
- 15.Hobbs JR. IgM deficiency. Birth Defects Orig Artic Ser. 1975;11:112–6.PubMedGoogle Scholar
- 16.Blecher TE, Brzechwa-Ajdukiewicz A, McCarthy CF, Read AE. Serum immunoglobulins and lymphocyte transformation studies in coeliac disease. Gut. 1969;10:57–62.CrossRefPubMedGoogle Scholar
- 17.Kimura S, Tanigawa M, Nakahashi Y, Inoue M, Yamamura Y, Kato H, et al. Selective IgM deficiency in a patient with Hashimoto’s disease. Intern Med. 1993;32:302–7.CrossRefPubMedGoogle Scholar
- 18.Komatsu K, Hamano H, Ochi Y, Takayama M, Muraki T, Yoshizawa K, et al. High prevalence of hypothyroidism in patients with autoimmune pancreatitis. Dig Dis Sci. 2005;50:1052–7.CrossRefPubMedGoogle Scholar
- 19.Raziuddin S, Danial HB, Kelley M. OKT4+ T cell abnormality in patients with active systemic lupus erythematosus: HLA-DR antigen expressions. Clin Immunol Immunopathol. 1988;48:42–9.CrossRefPubMedGoogle Scholar
- 20.Takeuchi T, Nakagawa T, Maeda Y, Hirano S, Sasaki-Hayashi M, Makino S, et al. Functional defect of B lymphocytes in a patient with selective IgM deficiency associated with systemic lupus erythematosus. Autoimmunity. 2001;34:115–22.PubMedCrossRefGoogle Scholar
- 21.Boes M, Schmidt T, Linkemann K, Beaudette BC, Marshak-Rothstein A, Chen J. Accelerated development of IgG autoantibodies and autoimmune disease in the absence of secreted IgM. Proc Natl Acad Sci USA. 2000;97:1184–9.CrossRefPubMedGoogle Scholar
- 22.Botto M, Dell’Agnola C, Bygrave AE, Thompson EM, Cook HT, Petry F, et al. Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat Genet. 1998;19:56–9.CrossRefPubMedGoogle Scholar
- 23.Muraki T, Hamano H, Ochi Y, Komatsu K, Komiyama Y, Arakura N, et al. Autoimmune pancreatitis and complement activation system. Pancreas. 2006;32:16–21.CrossRefPubMedGoogle Scholar
- 24.Mestecky J, Russell MW, Elson CO. Intestinal IgA: novel views on its function in the defence of the largest mucosal surface. Gut. 1999;44:2–5.PubMedCrossRefGoogle Scholar
- 25.Jacob CM, Pastorino AC, Fahl K, Carneiro-Sampaio M, Monteiro RC. Autoimmunity in IgA deficiency: revisiting the role of IgA as a silent housekeeper. J Clin Immunol. 2008;28(Suppl 1):S56–61.CrossRefPubMedGoogle Scholar
- 26.Carneiro-Sampaio M, Coutinho A. Tolerance and autoimmunity: lessons at the bedside of primary immunodeficiencies. Adv Immunol. 2007;95:51–82.CrossRefPubMedGoogle Scholar
- 27.Goldstein MF, Goldstein AL, Dunsky EH, Dvorin DJ, Belecanech GA, Shamir K. Pediatric selective IgM immunodeficiency. Clin Dev Immunol. 2008;2008:624850.PubMedGoogle Scholar
- 28.Hammarstrom L, Vorechovsky I, Webster D. Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID). Clin Exp Immunol. 2000;120:225–31.CrossRefPubMedGoogle Scholar
- 29.Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids new mechanisms for old drugs. N Engl J Med. 2005;353:1711–23.CrossRefPubMedGoogle Scholar