High serum IgG4 concentrations in patients with sclerosing pancreatitis.
08 Mar 2001-The New England Journal of Medicine (Massachusetts Medical Society)-Vol. 344, Iss: 10, pp 732-738
TL;DR: Patients with sclerosing pancreatitis have high serum IgG4 concentrations, providing a useful means of distinguishing this disorder from other diseases of the pancreas or biliary tract.
Abstract: Background Sclerosing pancreatitis is a unique form of pancreatitis that is characterized by irregular narrowing of the main pancreatic duct, lymphoplasmacytic inflammation of the pancreas, and hypergammaglobulinemia and that responds to glucocorticoid treatment. Preliminary studies suggested that serum IgG4 concentrations are elevated in this disease but not in other diseases of the pancreas or biliary tract. Methods We measured serum IgG4 concentrations using single radial immunodiffusion and an enzyme-linked immunosorbent assay in 20 patients with sclerosing pancreatitis, 20 age- and sex-matched normal subjects, and 154 patients with pancreatic cancer, ordinary chronic pancreatitis, primary biliary cirrhosis, primary sclerosing cholangitis, or Sjogren's syndrome. Serum concentrations of immune complexes and the IgG4 subclass of immune complexes were determined by means of an enzyme-linked immunosorbent assay with monoclonal rheumatoid factor. Results The median serum IgG4 concentration in the patients ...
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Harvard University1, University of Cambridge2, Mayo Clinic3, Okayama University4, Technische Universität München5, Dalhousie University6, University of Amsterdam7, Southampton General Hospital8, Tokyo Metropolitan Komagome Hospital9, Shinshu University10, Kanazawa University11, Kanazawa Medical University12, Kansai Medical University13, Seoul National University14, University College London15, Sapporo Medical University16, University of Verona17
TL;DR: This statement proposes a terminology scheme for the diagnosis of IgG4-related disease that is based primarily on the morphological appearance on biopsy, and advocates the use of strict criteria for accepting newly proposed entities or sites as components of the IgG 4- related disease spectrum.
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1,948 citations
Kanazawa Medical University1, Kansai Medical University2, Kanazawa University3, Sapporo Medical University4, University of Toyama5, Okayama University6, Nagoya University7, Shinshu University8, Tokyo Metropolitan Komagome Hospital9, Tohoku University10, Kyushu University11, University of Tsukuba12, Kyoto University13, Keio University14, Kagoshima University15, Fujita Health University16, Nagoya City University17
TL;DR: The comprehensive diagnostic criteria for IgG4-RD are practically useful for general physicians and nonspecialists and have increased the sensitivity of diagnosis to 100% for Igg4-related MD, KD, and AIP.
Abstract: IgG4-related disease (IgG4-RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4+ plasma cells Although IgG4-RD is not rare and is clinically important, its clinical diagnostic criteria have not been established Comprehensive diagnostic criteria for IgG4-RD, including the involvement of various organs, are intended for the practical use of general physicians and nonspecialists Two IgG4-RD study groups, the Umehara and Okazaki teams, were organized by the Ministry of Health, Labor and Welfare Japan As IgG4-RD comprises a wide variety of diseases, these groups consist of physicians and researchers in various disciplines, including rheumatology, hematology, gastroenterology, nephrology, pulmonology, ophthalmology, odontology, pathology, statistics, and basic and molecular immunology throughout Japan, with 66 and 56 members of the Umehara and Okazaki teams, respectively Collaborations of the two study groups involved detailed analyses of clinical symptoms, laboratory results, and biopsy specimens of patients with IgG4-RD, resulting in the establishment of comprehensive diagnostic criteria for IgG4-RD Although many patients with IgG4-RD have lesions in several organs, either synchronously or metachronously, and the pathological features of each organ differ, consensus has been reached on two diagnostic criteria for IgG4RD: (1) serum IgG4 concentration >135 mg/dl, and (2) >40% of IgG+ plasma cells being IgG4+ and >10 cells/high powered field of biopsy sample Although the comprehensive diagnostic criteria are not sufficiently sensitive for the diagnosis of type 1 IgG4-related autoimmune pancreatitis (IgG4-related AIP), they are adequately sensitive for IgG4-related Mikulicz’s disease (MD) and kidney disease (KD) In addition, the comprehensive diagnostic criteria, combined with organ-specific diagnostic criteria, have increased the sensitivity of diagnosis to 100% for IgG4-related MD, KD, and AIP Our comprehensive diagnostic criteria for IgG4-RD are practically useful for general physicians and nonspecialists
1,417 citations
Cites methods from "High serum IgG4 concentrations in p..."
...The cutoff value for serum IgG4 concentration, 135 mg/dl, was based on receiver operating characteristic (ROC) curves, and its validity was confirmed in patients with AIP [26, 28]....
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TL;DR: It is suggested that AIP is not simply pancreatitis but that it is a pancreatic lesion involved in IgG4-related systemic disease with extensive organ involvement, and a new clinicopathological entity is proposed.
Abstract: Autoimmune pancreatitis (AIP) is occasionally associated with other autoimmune diseases. To investigate the pathophysiology of AIP, we immunohistochemically examined the pancreas and other organs in eight patients with AIP, and in controls, using anti-CD4-T and CD8-T cell subsets, as well as IgG4 antibodies. In AIP patients, severe or moderate infiltration of IgG4-positive plasma cells associated with CD4- or CD8-positive T lymphocytes was detected in the peripancreatic tissue (6/6), bile duct (8/8), gallbladder (8/8), portal area of the liver (3/3), gastric mucosa (5/7), colonic mucosa (2/2), salivary glands (1/2), lymph nodes (6/6), and bone marrow (2/2), as well as in the pancreas (8/8). There were few IgG4-positive plasma cells at the same sites in controls. These results suggest that AIP is not simply pancreatitis but that it is a pancreatic lesion involved in IgG4-related systemic disease with extensive organ involvement. We propose a new clinicopathological entity, of a systemic IgG4-related autoimmune disease in which AIP and its associated diseases might be involved.
1,242 citations
TL;DR: The categorization of AIP into types 1 and 2 should be helpful for further clarification of the clinical features, pathogenesis, and natural history of these diseases.
Abstract: Objectives:To achieve the goal of developing international consensus diagnostic criteria (ICDC) for autoimmune pancreatitis (AIP).Methods:An international panel of experts met during the 14th Congress of the International Association of Pancreatology held in Fukuoka, Japan, from July 11 through 13,
1,232 citations
References
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TL;DR: A representation and interpretation of the area under a receiver operating characteristic (ROC) curve obtained by the "rating" method, or by mathematical predictions based on patient characteristics, is presented and it is shown that in such a setting the area represents the probability that a randomly chosen diseased subject is (correctly) rated or ranked with greater suspicion than a random chosen non-diseased subject.
Abstract: A representation and interpretation of the area under a receiver operating characteristic (ROC) curve obtained by the "rating" method, or by mathematical predictions based on patient characteristics, is presented. It is shown that in such a setting the area represents the probability that a randomly chosen diseased subject is (correctly) rated or ranked with greater suspicion than a randomly chosen non-diseased subject. Moreover, this probability of a correct ranking is the same quantity that is estimated by the already well-studied nonparametric Wilcoxon statistic. These two relationships are exploited to (a) provide rapid closed-form expressions for the approximate magnitude of the sampling variability, i.e., standard error that one uses to accompany the area under a smoothed ROC curve, (b) guide in determining the size of the sample required to provide a sufficiently reliable estimate of this area, and (c) determine how large sample sizes should be to ensure that one can statistically detect difference...
19,398 citations
TL;DR: Receiver-operating characteristic (ROC) plots provide a pure index of accuracy by demonstrating the limits of a test's ability to discriminate between alternative states of health over the complete spectrum of operating conditions.
Abstract: The clinical performance of a laboratory test can be described in terms of diagnostic accuracy, or the ability to correctly classify subjects into clinically relevant subgroups. Diagnostic accuracy refers to the quality of the information provided by the classification device and should be distinguished from the usefulness, or actual practical value, of the information. Receiver-operating characteristic (ROC) plots provide a pure index of accuracy by demonstrating the limits of a test's ability to discriminate between alternative states of health over the complete spectrum of operating conditions. Furthermore, ROC plots occupy a central or unifying position in the process of assessing and using diagnostic tools. Once the plot is generated, a user can readily go on to many other activities such as performing quantitative ROC analysis and comparisons of tests, using likelihood ratio to revise the probability of disease in individual subjects, selecting decision thresholds, using logistic-regression analysis, using discriminant-function analysis, or incorporating the tool into a clinical strategy by using decision analysis.
6,339 citations
Additional excerpts
...ELISA 51 (15, 128) 41 (14, 156) 663 (136, 1150) 597 ( 24 , 1230) <0.001 <0.001...
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TL;DR: Bernard Rosner's FUNDAMENTALS of BIOSTATISTICS is a practical introduction to the methods, techniques, and computation of statistics with human subjects that prepares students for their future courses and careers.
Abstract: Bernard Rosner's FUNDAMENTALS OF BIOSTATISTICS is a practical introduction to the methods, techniques, and computation of statistics with human subjects. It prepares students for their future courses and careers by introducing the statistical methods most often used in medical literature. Rosner minimizes the amount of mathematical formulation (algebra-based) while still giving complete explanations of all the important concepts. As in previous editions, a major strength of this book is that every new concept is developed systematically through completely worked out examples from current medical research problems.
4,624 citations
Book•
01 Jan 1982
TL;DR: Bernard Rosner's "Fundamentals of BIOSTATISTICS" as mentioned in this paper is a practical introduction to the methods, techniques, and computation of statistics with human subjects.
Abstract: Bernard Rosner's FUNDAMENTALS OF BIOSTATISTICS is a practical introduction to the methods, techniques, and computation of statistics with human subjects. It prepares students for their future courses and careers by introducing the statistical methods most often used in medical literature. Rosner minimizes the amount of mathematical formulation (algebra-based) while still giving complete explanations of all the important concepts. As in previous editions, a major strength of this book is that every new concept is developed systematically through completely worked out examples from current medical research problems.
4,438 citations
TL;DR: In this paper, the authors reported a case of chronic pancreatitis in which an autoimmune mechanism is involved in the etiology and summarized the cases of pancreatitis suspected of being caused by an auto-antibody-positive mechanism in the Japanese and English literature.
Abstract: Several authors have reported a case of chronic pancreatitis associated with Sjogren's syndrome in which an autoimmune mechanism may have been involved in the etiology and in which steroid therapy was effective. We recently encountered a patient with pancreatitis who had hyperglobulinemia, was autoantibody-positive, and responded to steroid therapy. This patient, however, failed to show any evidence of association with Sjogren's syndrome or other collagen diseases. Although the concept of autoimmune hepatitis and the criteria for diagnosing it have been established, autoimmune pancreatitis has not yet been defined as a clinical entity. We report a case of chronic pancreatitis in which an autoimmune mechanism is involved in the etiology and summarize the cases of pancreatitis suspected of being caused by an autoimmune mechanism in the Japanese and English literature.
1,297 citations