Serum immunoglobulin G4 associated with number and distribution of extrapancreatic lesions in type 1 autoimmune pancreatitis patients

Kaji, Ryohei; Takedatsu, Hidetoshi; Okabe, Yoshinobu; Ishida, Yusuke; Sugiyama, Gen; Yonemoto, Koji; Mitsuyama, Keiichi; Takahashi, Osamu; Sata, Michio

doi:10.1111/j.1440-1746.2011.06933.x

Cited by 17 publications

(13 citation statements)

References 25 publications

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“…That is, patients with elevated serum IgG4 concentrations denote a large subset of patients with IgG4-RD whose disease is characterized by more extensive organ involvement, high inflammatory markers, low complement levels, and (possibly) greater refractoriness to treatment as compared with patients with normal IgG4 levels. [11][12][13][14] In a study of patients with autoimmune pancreatitis, Matsubayashi et al 11 reported a higher frequency of certain symptoms (eg, jaundice) and number of extrahepatic lesions together with a large size of pancreatic lesions in patients with higher IgG4 levels.…”

Section: Serum Igg4 Levelsmentioning

confidence: 98%

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Diagnostic Approach to the Complexity of IgG4-Related Disease

Stone

Brito-Zerón

Bosch

et al. 2015

Mayo Clinic Proceedings

154

224

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IgG4-related disease (IgG4-RD) is a systemic disease characterized by the infiltration of IgG4-bearing plasma cells and, more importantly, distinctive histopathological features: storiform fibrosis, obliterative phlebitis, a lymphoplasmacytic infiltrate, and mild-to-moderate tissue eosinophilia. The diagnostic approach is complex and relies on the coexistence of various clinical, laboratory, and histopathological findings, none of which is pathognomonic in and of itself. IgG4-related disease should be suspected in patients presenting with unexplained enlargement or swelling of 1 or more organs or tissue organs. Four laboratory abnormalities often provide initial clues to the diagnosis of IgG4-RD: peripheral eosinophilia, hypergammaglobulinemia, elevated serum IgE levels, and hypocomplementemia. Elevated serum IgG4 levels provided critical information in identifying the first cases of IgG4-RD, but recent studies have reported substantial limitations to the measurement of serum IgG4 concentrations, precluding reliance on serum IgG4 concentrations for diagnostic purposes. In contrast, new studies have suggested a promising role of flow cytometry studies in the diagnosis and longitudinal management of IgG4-RD. Demonstration of the classic histopathological features of IgG4-RD remains crucial to diagnosis in most cases, and biopsy proof is preferred strongly by most disease experts before the initiation of treatment. Of note, the multiorgan nature of IgG4-RD was first established in 2003. This review intends to provide most recent knowledge about the clinical, laboratory, radiological, and pathological characteristics of IgG4-RD that may guide the physician to establish an early diagnosis. We searched PubMed and MEDLINE for relevant articles published between January 1, 2000, and November 1, 2014, using the search terms IgG4 and IgG4-related.

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Section: Serum Igg4 Levelsmentioning

confidence: 98%

“…None of these features is pathognomonic of IgG4-RD, however, and even elevated IgG4 levels have been reported in a wide range of diseases (Table 3). 14,[66][67][68][69][70] In addition, limitations about its test characteristics preclude reliance on measurements of serum IgG4 levels for the purpose of diagnosis.…”

Section: Differential Diagnosismentioning

confidence: 98%

Diagnostic Approach to the Complexity of IgG4-Related Disease

Stone

Brito-Zerón

Bosch

et al. 2015

Mayo Clinic Proceedings

154

224

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“…Firstly, there was inevitable heterogeneity in the meta-analysis of diagnostic accuracy due to the variability in design characteristics and the poor quality of reporting in the primary studies. The quality of the studies included in the meta-analysis was modest for our meta-analysis because ten studies were retrospective designed19232425262728293334, six studies were prospective designed111618303536, and seven studies did not report the study design291015173738. The QUADAS-2 tools for the methodological assessment indicated that other contributors to the potential heterogeneity across the studies result from the risk bias in patient selection due to the diagnosis of IgG4-RD on the basis of multiple criteria, as well as due to the detection method for serum IgG4 despite the clear cut-off value given in several studies2425262728.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, IgG4-RD is a rare disorder with low incidence compared with other autoimmune disease, and the small sample sizes in previous studies focusing on the features of serum IgG4 level frequently led to a variable diagnostic accuracy of IgG4 in patients with IgG4-RD6915. Notably, IgG4-RD is a systemic fibro-inflammatory disease that has a similar pathogenesis and cardinal features in affected organs; however, it was rarely analysed as an extensive entity but rather an individual disorder focused on a single organ, especially the pancreas and salivary or lacrimal glands21116171819.…”

mentioning

confidence: 99%

Diagnostic performance of serum IgG4 level for IgG4-related disease: a meta-analysis

Ling

Wang³

et al. 2016

Sci Rep

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An elevated serum IgG4 level is one of the most useful factors in the diagnosis of IgG4-related disease (IgG4-RD). In this study, we performed a meta-analysis of the published articles assessing the diagnostic accuracy of serum IgG4 concentrations for IgG4-RD. The databases of MEDLINE/PubMed, EMBASE and Web of Science were systematically searched for relevant studies. Sensitivities and specificities of serum IgG4 in each study were calculated, and the hierarchical summary receiver operating characteristic (HSROC) model with a random effects model were employed to obtain the individual and pooled estimates of sensitivities and specificities. In total, twenty-three studies comprising 6048 patients with IgG4-RD were included in the meta-analysis. The pooled sensitivity was 85% with a 95% confidence interval (CI) of 78–90%; the pooled specificity was 93% with a 95% CI of 90–95%. The HSROC curve for quantitative serum IgG4 lies closer to the upper left corner of the plot, and the area under the curve (AUC) was 0.95 (95% CI 0.93, 0.97), which suggested a high diagnostic accuracy of serum IgG4 for the entity of IgG4-RD. Our study suggests that serum IgG4 has high sensitivity and specificity in the diagnosis of IgG4-RD.

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“…For serum IgG4 levels, the sensitivity and specificity were 78.7% and 87.7%, respectively, which are not as high as the initial study by Hamano et al 26 , but are close to the reports by Ghazale et al 9 and other previous reports 10 11 12 . The differences in the diagnostic values of serum IgG4 for AIP could be attributed to differences in the patients enrolled in the studies, or differences in the disease activity of the cases selected 27 28 .…”

Section: Discussionmentioning

confidence: 99%

Hybrid kappa\lambda antibody is a new serological marker to diagnose autoimmune pancreatitis and differentiate it from pancreatic cancer

Hao

et al. 2016

Sci Rep

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The only generally accepted serological marker currently used for the diagnosis of autoimmune pancreatitis (AIP) is IgG4. Our aim was mainly to determine whether hybrid κ\λ antibody can help to diagnose AIP and to differentiate it from pancreatic cancer. We established an enzyme-linked immunosorbent assay (ELISA) system to measure the levels of hybrid κ\λ antibodies in human sera. Sera were obtained from 338 patients, including 61 with AIP, 74 with pancreatic cancer, 50 with acute pancreatitis, 40 with ordinary chronic pancreatitis, 15 with miscellaneous pancreatic diseases, and 98 with normal pancreas. Our study showed levels of hybrid κ\λ antibodies in the AIP group were significantly higher than in the non-AIP group (P < 0.001). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of AIP were 80.3%, 91%, 66.2% and 95.5% respectively. Furthermore, the combined measurement of serum hybrid κ\λ antibody and IgG4 tended to increase the sensitivity although the difference was not statistically significant (90.2% vs. 78.7%, P = 0.08), compared to measurement of IgG4 alone. Our findings suggest that hybrid κ\λ antibody could be a new serological marker to diagnose AIP and differentiate it from pancreatic cancer.

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Serum immunoglobulin G4 associated with number and distribution of extrapancreatic lesions in type 1 autoimmune pancreatitis patients

Abstract: Our findings indicated that serum IgG4 was useful in both the diagnosis of type 1 AIP and the detection of systemic EPL. Our finding may help the concept and diagnostic criteria of IgG4-related disease with type 1 AIP.

Cited by 17 publications

References 25 publications

Diagnostic Approach to the Complexity of IgG4-Related Disease

Diagnostic Approach to the Complexity of IgG4-Related Disease

Diagnostic performance of serum IgG4 level for IgG4-related disease: a meta-analysis

Hybrid kappa\lambda antibody is a new serological marker to diagnose autoimmune pancreatitis and differentiate it from pancreatic cancer

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