Fifth International Serum Exchange Workshop for Insulin Autoantibody (IAA) Standardization

Greenbaum, Carla J.; Wilkin, Terence J.; Palmer, Jerry P.; Agopian, Melkon S.; Villena, Antonio Arnaiz; Becker, Dorothy J.; Becker, Frank; Bosi, Emanuele; Bottazzo, G. F.; Bouix, O.; Colman, Peter G; Dawkins, R. L.; Leiva, Alberto de; Dean, B M; Dimario, Umberto; Eisenbarth, George S.; Elliot, R. B.; Gorus, Frans; Huang, Wujiao; Humbel, René‐Louis; Juliá, M. R.; Karjalainen, J.; Keilacker, H; Kuglin, B.; Kwan, Jennifer; Marchal, Cécile; Maclaren, Noel K.; McEvoy, Robert; Molenaar, J Jaap; Reinauer, K. M.; Scherbaum, Werner A.; Sodoyez, J. C.; Vialettes, B.; Zanchetta, R.; Ziegler, Anette G.

doi:10.1007/bf00429105

Cited by 26 publications

(18 citation statements)

References 6 publications

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“…Three patients tested positive for GAD antibodies, no patients tested positive for IA-2 antibodies and three patients tested weakly positive for insulin antibodies. Thus, the prevalence rates of antibodies against GAD, IA2 and insulin in the study population are not significantly different from those for the general population [7][8][9] or those for a population of patients with type 2 diabetes [11,12]. Moreover, antibody-positive patients were not diagnosed with diabetes, and none of the subjects tested positive for more than one antibody, a result that is generally considered to be highly predictive of type 1 diabetes.…”

Section: To the Editormentioning

confidence: 68%

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Immunological characteristics of diabetes in schizophrenia

2005

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Abbreviations IA2: insulinoma antigen 2 . LADA: latent autoimmune diabetes of adults To the EditorIn 1899, Henry Maudsley, the first psychiatrist to link diabetes to psychiatric illness, wrote that "diabetes is a disease which often shows itself in families in which insanity prevails" [1]. With this observation, Maudsley suggested that patients with schizophrenia are genetically predisposed to diabetes. The introduction of chlorpromazine (in 1953) and, more recently, the atypical antipsychotics was followed by an increase in the number of cases of new-onset diabetes and the worsening of glycaemic control in cases of existing diabetes in patients with schizophrenia [2]. These findings suggest an iatrogenic, rather than a genetic, origin of diabetes in schizophrenia, in the form of antipsychoticinduced weight gain. However, this debate has not, as yet, been settled.In general, diabetes associated with schizophrenia is classified as type 2 diabetes. However, there are two arguments against this classification. The first argument is the rapid onset of schizophrenia-associated diabetes: over 80% of patients who develop diabetes do so within 6 months of initiating antipsychotic therapy [2]. With such a rapid onset, weight gain is unlikely to be the main stimulus for the development of the diabetes. A prospective randomised trial comparing the classical antipsychotic haloperidol with the three atypicals clozapine, olanzapine and risperidone found no relationship between glucose change and weight gain at endpoint, thereby confirming the independence of these two measures [3]. The second argument is the dramatic clinical presentation of diabetes in schizophrenia. There is an enhanced risk of metabolic complications, such as ketosis, acidosis and ketoacidosis, which are associated with a mortality rate of 26.5% [4][5][6]. These features are suggestive of type 1 diabetes or latent autoimmune diabetes of adults (LADA) rather than type 2 diabetes.Type 1 diabetes and LADA are characterised by diabetes-related antibodies, i.e. antibodies against insulin, GAD and insulinoma antigen 2 (IA2), which are found in over 80% of type 1 diabetic subjects and in fewer than 5% of the general population [7,8]. The aim of this study was to determine the prevalence of the three diabetes-related antibodies in schizophrenic patients, thereby establishing whether autoimmune phenomena play a role in diabetes associated with schizophrenia.Patients (81 men [68.1%], 38 women [31.9%]; mean age 41.5 years [SD=10.9, range 19-65]) gave informed consent to participate in the study, which was approved by the Ethics Committee of the University of Utrecht. The psychiatric diagnosis was based on the shortened version of the

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Section: To the Editormentioning

confidence: 68%

“…After fasting overnight, patients underwent a standardised OGTT. Autoantibodies against GAD, IA-2, and insulin were measured in serum by RIAs [7][8][9]. Patients with pre-existing diabetes were exempt from the OGTT, but had blood samples taken for determination of autoantibodies.…”

Section: To the Editormentioning

confidence: 99%

Immunological characteristics of diabetes in schizophrenia

2005

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“…These diagnostic and predictive abilities did not naturally present themselves, as much of the early literature regarding autoantibodies in type 1 diabetes was subject to controversies and conflicting information-factors due in large part to variances in the methods and substrates used for autoantibody detection. Considerable advances toward overcoming these difficulties came through the voluntary performance of many investigators in more than a dozen international autoantibody workshops, often organized under the auspices of the Immunology of Diabetes Workshops, an organization that later became known as the Immunology of Diabetes Society (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Among their many findings, these workshops validated insulin, GAD, and IA-2 as autoantigens associated with type 1 diabetes in humans; identified sensitive and specific methods for autoantibody measurement; and introduced reference standards for diabetesassociated autoantibodies.…”

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confidence: 99%

International Workshop on Lessons From Animal Models for Human Type 1 Diabetes

Bonifacio¹,

et al. 2001

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Several self-antigens have been reported as targets of the autoimmune response in nonobese diabetic (NOD) mice. The aim of this workshop was to identify autoantibody assays that could provide useful markers of autoimmunity in this animal model for type 1 diabetes. More than 400 serum samples from NOD (4, 8, and 12 weeks of age and at diabetes onset), BALB/c, and B6 mice were collected from six separate animal facilities, coded, and distributed to five laboratories for autoantibody measurement. Insulin autoantibodies (IAA) were measured by radiobinding assay (RBA) by four laboratories and by enzyme-linked immunosorbent assay (ELISA) in one laboratory. Using the 99th percentile of BALB/c and B6 control mice as the threshold definition of positivity, IAA by RBA were detected in NOD mice at frequencies ranging from 10 to 30% at age 4 weeks, from 26 to 56% at 8 weeks, from 42 to 56% at 12 weeks, and from 15 to 75% at diabetes onset. With ELISA, IAA signals differed significantly between control mouse strains and increased with age in both control and NOD mice, with frequencies in NOD animals being 0% at 4 weeks, 14% at 8 weeks, 19% at 12 weeks, and 42% at diabetes onset. For IAA, the ELISA results were relatively discordant with those of RBA. GAD autoantibody (GADA) and IA-2 autoantibody (IA-2A) signals obtained by RBA were low (maximum 2.5% of total) but were increased in NOD mice compared with control mice at diabetes onset (GADA 29 -50%; IA-2A 36 -47%). ELISA also detected GADA (42%) and IA-2A

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“…Инсулин -маленькая молекула (масса всего 5800 Да); при сорбции ее конформация нарушается, и многие антигенные детерминанты становятся недоступными для сывороточных антител к инсулину. Низкая ДЧ им-муноферментных тест-систем для определения IA, рабо-тающих по описанному выше принципу, неоднократно отмечалась в литературе [13,14].…”

Section: сахарный диабет Diabetes Mellitusunclassified

Diagnostic value of islet autoantibody assays practised in Russia. 1. Classic immunofluorescence islet cell antibody assay, immunoradiometric glutamic acid decarboxylase antibody assay, and ELISA tyrosine phosphatase antibody and insulin antibody assays

Timofeev¹,

Валентинович²,

Gorst³

et al. 2016

Diabetes mellitus

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Objective. To estimate performance characteristics and diagnostic value of immunofluorescent islet cell antibody (ICA) assay, immunoradiometric glutamic acid decarboxylase antibody (GADA) assay, and ELISA tyrosine phosphatase IA-2 antibody (IA-2A) and insulin antibody (IA) assays.Research Design and Methods. Antibodies were tested in 438 children and adolescents with newly diagnosed diabetes mellitus (DM) type 1, and in 891 subjects without DM type 1. ICA were determined by the classic indirect immunofluorescent method recommended by the Juvenile Diabetes Foundation International, GADA were determined with the Immunotech IRMA Anti-GAD kit, and IA-2A and IA were determined with Medizym Anti-IA2 and Orgentec Anti-Insulin ELISA kits, respectively. Sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of the tests were estimated with contingency tables. Diagnostic accuracy was estimated from areas under receiver operating curves (AUC).Results. ICA test was of the greatest diagnostic value (Se=88%, Sp=96%, PPV=96%, NPV=94%, AUC=0,94), followed by IA-2A (Se=66%, Sp=98%, PPV=98%, NPV=59%, AUC=0,82) and GADA (Se=73%, Sp=84%, PPV=75%, NPV=83%, AUC=0,79). IA test exhibited a very low Se (4,3%) and lacked diagnostic accuracy (AUC=0,5).Conclusions. We recommend to use ICA, IA-2A and GADA tests surveyed in our study for diagnosis of DM type 1 and differential diagnosis of DM. We don’t recommend IA testing with an Orgentec Anti-Insulin ELISA kit for usage in clinical practice.

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Fifth International Serum Exchange Workshop for Insulin Autoantibody (IAA) Standardization

Abstract: Report prepared by C.J. Greenbaum 1, T. J. Wilkin 2 and J. P. Palmer 1 on behalf of the Immunology and Diabetes Workshops and participating laboratories*

Cited by 26 publications

References 6 publications

Immunological characteristics of diabetes in schizophrenia

Immunological characteristics of diabetes in schizophrenia

International Workshop on Lessons From Animal Models for Human Type 1 Diabetes

Diagnostic value of islet autoantibody assays practised in Russia. 1. Classic immunofluorescence islet cell antibody assay, immunoradiometric glutamic acid decarboxylase antibody assay, and ELISA tyrosine phosphatase antibody and insulin antibody assays

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