Serology

Serum markers associated with autoimmune pancreatitis (AIP) are roughly classified as immunoglobulins, autoantibodies, complement, and activity markers for lymphoid cells. These markers have been used for the diagnosis of AIP, differentiation of AIP from

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Serology Shigeyuki Kawa, Takayuki Watanabe, and Takashi Muraki

Introduction Serum markers associated with autoimmune pancreatitis (AIP) are roughly classified as immunoglobulins, autoantibodies, complement, and activity markers for lymphoid cells. These markers have been used for the diagnosis of AIP, differentiation of AIP from pancreatic cancer, prediction of AIP recurrence, and estimation of AIP disease activity in clinical follow-up assessments [1]. Among these markers, IgG4 is recognized to be specifically associated with AIP; thus, it is a characteristic indicator with high clinical utility [2]. Many studies have focused on the association between AIP and IgG4. However, other markers also represent useful tools in the various clinical aspects of AIP. In the following sections, we describe the clinical significance of these markers.

We compared the rates of positive detection for each marker (Table 9.1) and found that IgG4 provided the best result.

Immunoglobulins IgG4 The sera of patients with AIP exhibited a polyclonal band in the rapidly migrating fraction of gel electrophoresis that contained γ-globulins; this resulted in the finding that β−γ globulin bridging was a characteristic of AIP. Immunoprecipitation assays revealed that this polyclonal band was the result of high serum concentrations of IgG4 [2]. IgG4 is typically a minor component in IgG

Diagnosis

Table 9.1 Rates of detection for each serum marker in autoimmune pancreatitis

Marker Sensitivities

Marker Immunoglobulins IgG4 IgG IgE IgA IgM Autoantibodies Antinuclear antibody (ANA) Rheumatoid factor (RF) Anti-SSA(Ro) antibody Anti-SSB(La) antibody Antimitochondrial antibody (AMA) Complement components and immune complex C3 C4 Circulating immune complex (CIC) Activity markers for lymphoid cells Soluble interleukin-2 receptor (sIL-2R) β2 microglobulin (β2-m)

Many serum markers have been assessed for their utility in diagnosing AIP, and many are included in diagnostic criteria for AIP. The first diagnostic criteria for AIP were published by the Japanese Pancreas Society (2002). Those criteria included laboratory data that demonstrated abnormally elevated levels of serum γ-globulin and/or IgG or the presence of autoantibodies [3]. After the clinical usefulness of IgG4 was discovered [2], most diagnostic criteria for AIP in Japan and other countries included only IgG4 as a diagnostic serum marker [4–10].

S. Kawa, MD, PhD (*) Center for Health, Safety, and Environmental Management, Shinshu University, 3-1-1 Asahi, Matsumoto 390-8621, Japan e-mail: [email protected] T. Watanabe, MD, PhD • T. Muraki, MD, PhD Department of Gastroenterology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan

T. Kamisawa, J.B. Chung (eds.), Autoimmune Pancreatitis, DOI 10.1007/978-3-642-55086-7_9, © Springer-Verlag Berlin Heidelberg 2015

Positive/total (n)

%

80/88 59/88 33/83 7/88 4/88

90.9 67.0 39.8 8.0 4.5

39/74 18/67 0/56 0/56 2/47

52.7 23.9 0.0 0.0 4.3

29/84 27/84 68/82

34.5 32.1 82.9

68/81 62/82

84.0 75.6

61

62 Fig.