Usefulness of serum IgG4 in the diagnosis and follow up of autoimmune pancreatitis: A systematic literature review and meta‐analysis

Abstract

High circulating serum immunoglobulin G4 (IgG4) levels have been proposed as a marker of autoimmune pancreatitis (AIP). The aim of the present study was to review the data existing in the English literature on the usefulness of the IgG4 serum levels in the diagnosis and follow up of patients with AIP. A total of 159 patients with AIP and 1099 controls were described in seven selected papers reporting the usefulness of serum IgG4 in diagnosing AIP. In total, 304 controls had pancreatic cancer, 96 had autoimmune diseases, and the remaining 699 had other conditions. The summary receiver-operating characteristic curve analysis was carried out by means of Meta-DiSc open-access software. Serum IgG4 showed good accuracy in distinguishing between AIP and the overall controls, pancreatic cancer and other autoimmune diseases (area under the curve [Ϯ SE]: 0.920 Ϯ 0.073, 0.914 Ϯ 0.191, and 0.949 Ϯ 0.024, respectively). The studies analyzed showed significantly heterogeneous specificity values in each of the three analyses performed. The analysis of the four studies comparing AIP and pancreatic cancers also showed significantly heterogeneous values of sensitivities and odds ratios. Regarding the usefulness of IgG4 as a marker of efficacy of steroid treatment, a decrease in the serum concentrations of IgG4 was found in the four available studies. The serum IgG4 subclass is a good marker of AIP, and its determination should be included in the diagnostic workup of this disease. However, the heterogeneity of the studies published until now means that more studies are necessary in order to better evaluate the true accuracy of IgG4 in discriminating AIP versus other autoimmune diseases.

Brief Report: Spuriously Low Serum IgG4 Concentrations Caused by the Prozone Phenomenon in Patients With IgG4‐Related Disease

“…Wide variability exists in the reported frequency of elevated serum IgG4 levels (14)(15)(16)(17)(18), and the reliability of the serum IgG4 concentration as a biomarker for diagnosis and disease activity has been questioned. Although the prozone effect appears to explain a substantial number of false-negative results of serum IgG4 assays, the cumulative literature and our own experience suggest the existence of patients with biopsy-proven IgG4-RD and normal serum IgG4 concentrations.…”

Autoimmune pancreatitis : An entity difficult to diagnose

“…Pathogenesis of AIP is not completely understood but involves autoimmune mechanisms such as hyper agammaglobulinemia, increased serum levels of IgG4 and development of autoantibodies against lactoferrin and carbonic anhydrase II. AIP has two distinct typestype 1, is lymphoplasmacytic sclerosing pancreatitis presenting with diffuse swelling of the pancreas, raised serum levels of IgG, frequently associated with other autoimmune-related diseases [4][5][6]. AIP type 2 presents in younger age group and has pathognomonic duct-centric pancreatitis [7].…”

Autoimmune pancreatitis as a systemic, protracted and potentially fatal disease

“…W badaniach laboratoryjnych stwierdza się wzrost aktywności enzymów cholestatycznych, niewielki i okresowo występujący wzrost aktywności lipazy i amylazy, zwiększenie stężenia γ-globulin, immunoglobuliny klasy G lub podklasy IgG 4 . Stężenie IgG 4 powyżej 135 mg/dl charakteryzuje się czułością i swoistością diagnostyczną w granicach 66,7-94,3% [6,12,18,20]. Stężenie IgG 4 koreluje z aktywnością choroby, dlatego wykorzystywane jest zarówno w diagnostyce, jak i ocenie skuteczności leczenia, jednak u niektórych chorych może się także zmniejszać spontanicznie bez terapii [20].…”

“…Stężenie IgG 4 powyżej 135 mg/dl charakteryzuje się czułością i swoistością diagnostyczną w granicach 66,7-94,3% [6,12,18,20]. Stężenie IgG 4 koreluje z aktywnością choroby, dlatego wykorzystywane jest zarówno w diagnostyce, jak i ocenie skuteczności leczenia, jednak u niektórych chorych może się także zmniejszać spontanicznie bez terapii [20]. W panelu badań immunologicznych często stwierdza się obecność przeciwciał przeciw laktoferynie, anhydrazie węglanowej II i IV, czynnika reumatoidalnego, ANA, ASMA i rzadziej AMA [1,10].…”