scholarly journals Differential diagnostic utilities of combined testing for islet cell antibody, glutamic acid decarboxylase antibody, and tyrosine phosphatase antibody

2018 ◽  
Vol 21 (2) ◽  
pp. 74-83
Author(s):  
Alexei V. Timofeev ◽  
Igor E. Koltunov ◽  
Elena E. Petriaikina ◽  
Irina G. Rybkina ◽  
Lubov N. Samsonova ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Islet Cells ◽  
Autoimmune Diabetes ◽  
Tyrosine Phosphatase ◽  
Islet Cell Antibody ◽  
Acid Decarboxylase ◽  
Triple Combination ◽  
Radioimmune Assay ◽  
Cell Antibody ◽  
Posttest Probability

Background. Beta-cell antibody tests are used for the differential diagnosis of diabetes mellitus. They permit to discriminate between the type 1 diabetes (T1D) and non-autoimmune diabetes types. To choose an appropriate test for ruling in or ruling out the T1D a physician needs to know how conclusive test results are. The most powerful estimate of test conclusiveness is its likelihood ratio (LHR). The higher LHR of a positive result (LHR+), the more posttest probability of T1D; the lower LHR of a negative result (LHR), the less posttest probability of T1D. Aims. To compare conclusiveness of single and combined tests for antibodies to islet cells (ICA), glutamate decarboxylase (GADA), and tyrosine phosphatase IA-2 (IA-2A), and to evaluate posttest probabilities of T1D at various pretest probabilities. Methods. All antibodies were tested in parallel in 169 children and adolescents with a new-onset T1D, and in 169 persons without this disease. ICA, GADA, and IA-2A were determined by indirect immunofluorescence, radioimmune assay, and ELISA, respectively. LHR+ and LHR were calculated with the MedCalc Statistical Software. Posttest T1D probabilities were calculated from Bayes theorem-based equation. Results. Among single tests, an ICA test had the greatest LHR+ and the smallest LHR, and consequently was the most reliable either for ruling in or ruling out the T1D. Among test combinations, an ICAGADA combination had the greatest LHR+ and was the most suitable for T1D confirmation. The triple combination ICAGADAIA-2A had the smallest LHR and was the most suitable for T1D exclusion. Conclusions. In the differential diagnosis of diabetes, the most appropriate test for ruling in the T1D is the double combination ICAGADA. With both antibodies positive, this combination provides the highest posttest T1D probabilities at any pretest probability. The most appropriate test for ruling out the T1D is the triple combination ICAGADAIA-2A. With all three antibodies negative, this combination provides the lowest posttest T1D probabilities.

scholarly journals 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

2016 ◽  
Vol 19 (4) ◽  
pp. 331-340 ◽  
Author(s):  
Alexei V. Timofeev ◽  
Ksenia A. Gorst ◽  
Valentin Y. Uvarov ◽  
Ekaterina A. Pronina ◽  
Alisa V. Vitebskaya ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Islet Cell ◽  
Tyrosine Phosphatase ◽  
Diagnostic Value ◽  
Islet Cell Antibody ◽  
Acid Decarboxylase ◽  
Antibody Assay ◽  
Glutamic Acid Decarboxylase Antibody ◽  
Cell Antibody

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. 

scholarly journals 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.

10.14341/8032 ◽  
2016 ◽  
Vol 19 (4) ◽  
pp. 331
Author(s):  
Alexei V. Timofeev ◽  
Ksenia A. Gorst ◽  
Valentin Y. Uvarov ◽  
Ekaterina A. Pronina ◽  
Alisa V. Vitebskaya ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Islet Cell ◽  
Tyrosine Phosphatase ◽  
Diagnostic Value ◽  
Islet Cell Antibody ◽  
Acid Decarboxylase ◽  
Antibody Assay ◽  
Glutamic Acid Decarboxylase Antibody ◽  
Cell Antibody

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. 

scholarly journals Evaluation of Two Nonisotopic Immunoassays for Determination of Glutamic Acid Decarboxylase and Tyrosine Phosphatase Autoantibodies in Serum

2004 ◽  
Vol 50 (8) ◽  
pp. 1378-1382 ◽  
Author(s):  
Xavier Palomer ◽  
Dídac Mauricio ◽  
José Rodríguez-Espinosa ◽  
Edgar Zapico ◽  
Carme Mayoral ◽  
...  
Keyword(s):  
Glutamic Acid ◽  
Glutamic Acid Decarboxylase ◽  
Clinical Laboratory ◽  
Autoimmune Diabetes ◽  
Tyrosine Phosphatase ◽  
Acid Decarboxylase ◽  
Time Resolved ◽  
Radiobinding Assay

Abstract Background: Autoantibodies for the 65-kDa form of glutamic acid decarboxylase (GAD65) and protein tyrosine phosphatase-like protein (IA-2) are measured for risk prediction and diagnosis of autoimmune diabetes mellitus. There is a lack of adequate nonisotopic alternatives to the most widely used method for both autoantibodies, which is a radiobinding assay (RBA). Methods: We compared two commercially available immunoassays, an ELISA and a time-resolved immunofluorometric assay (TR-IFMA), with RBA. Results: We found excellent agreement between the RBA and ELISA for measurement of GAD65 autoantibodies (GADAs); they showed comparable analytical precision in the cutoff range and achieved similar diagnostic specificity. The ELISA identified more GADA-positive individuals among patients with new-onset type 1 diabetes than did the RBA [89% (95% confidence interval, 78–95%), vs 71% (58–82%); P <0.03]. For IA-2 autoantibodies (IA-2As), only the TR-IFMA achieved analytical performance and diagnostic accuracy comparable to that of the RBA. These results with the GADA ELISA and IA-2A TR-IFMA were consistent with those obtained blindly in the Diabetes Antibody Standardization Program 2003. The performance of the GADA TR-IFMA and IA-2A ELISA was unsatisfactory, and these tests were not subjected to clinical evaluation. Conclusions: The GADA ELISA and IA-2A TR-IFMA behave comparably with RBA and are thus suitable for use in the clinical laboratory.

CLINICAL AND IMMUNOLOGICAL ASPECTS OF VERIFICATION OF LATENT AUTOIMMUNE DIABETES IN ADULTS AT EARLY STAGES OF DISEASE MANIFESTATION

2021 ◽  
Vol 74 (7) ◽  
pp. 1707-1712
Author(s):  
Tetiana М. Tykhonova ◽  
Igor V. Belozоrov ◽  
Nadiya Ye. Barabash ◽  
Larysa O. Martymianova
Keyword(s):  
Autoimmune Diabetes ◽  
Tyrosine Phosphatase ◽  
Disease Onset ◽  
Acid Decarboxylase ◽  
Excess Body Weight ◽  
Disease Manifestation ◽  
Latent Autoimmune Diabetes ◽  
Immunological Examination ◽  
High Level

The aim: To establish diagnostic markers of LADA at the stage of manifestation based on the analysis of clinical and anamnestic data, the results of immunological examination of patients with different types of DM. Materials and methods: Study included 121 patients with LADA (1st (main) group), 60 patients with type 1 DM (2nd group), 81 patients with type 2 DM (3d group). The examination included analysis of complaints, medical history, determination of anthropometric data, studies of the level of antibodies to glutamic acid decarboxylase (GAD ab), cytoplasmic antigen (ICA ab), tyrosine phosphatase (IA-2 ab). Results: Criteria of LADA diagnosis included slow nature of DM course, the average age of the disease onset (45,02±9,96) years, combination of diabetic complaints with gradual weight loss, frequent detection of DM (64,46%) on request, fairly high level of glycemia at diagnosis ((14,12±4,57) mmol/l)), the possibility of ketonuria episodes in a certain amount (23,14%) of cases in the absence of acute ketoacidotic states. The presence of excess body weight and even obesity is not a criterion for excluding LADA. Conclusions: To verify the diagnosis of LADA it is necessary to study of at least two types of antibodies. The most conclusive is the determination of GAD ab and IA-2 ab.

scholarly journals Factors associated with increased irisin levels in the type 1 diabetes mellitus

2017 ◽  
Vol 51 (1) ◽  
pp. 1-7 ◽  
Author(s):  
I. Ates ◽  
M. F. Arikan ◽  
K. Erdogan ◽  
M. Kaplan ◽  
M. Yuksel ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Glycosylated Hemoglobin ◽  
Islet Cell Antibody ◽  
Acid Decarboxylase ◽  
Insulin Autoantibody ◽  
Cell Antibody ◽  
Positive Groups

Abstract Objective. The aim of the present study was to determine the irisin levels in patients with the type 1 diabetes mellitus (T1DM) and to examine the relation of irisin levels with the inflammation and autoimmunity.Methods. This study included 35 cases diagnosed with T1DM and 36 healthy volunteers. Antiglutamic acid decarboxylase (anti-GAD), islet cell antibody (ICA), and insulin autoantibody levels were measured in patients at the time when they were included into the study and recorded from the patient files. Serum irisin levels were measured by ELISA kit.Results. The median irisin levels were determined higher in T1DM group compared to the control one (6.8 ng/ml vs. 4.8 ng/ml, p=0.022; respectively). Median irisin levels were higher in anti-GAD (p=0.022) and ICA (p=0.044) positive groups compared to negative groups. In T1DM group, irisin levels displayed positive correlation with glycosylated hemoglobin (HbA1c) (r=0.377, p<0.001) and anti-GAD (r=0.392, p=0.020) and negative correlation with creatinine (r=-0390, p=0.021). In multivariate regression model, HbA1c (B±SE: 2.76±17683, p<0.001), and anti-GAD (B±SE: 2.311±0.610, p=0.001) were determined as independent predictors for predicting the irisin levels.Conclusion. In patients with T1DM, which chronic inflammation and autoimmunity take part in their etiopathogenesis, anti-GAD levels were an independent risk factor for the irisin. Th is may suggest that factors such as inflammation and autoimmunity can be effective in the synthesis of irisin.

scholarly journals Number of autoantibodies and HLA genotype, more than high titers of glutamic acid decarboxylase autoantibodies, predict insulin dependence in latent autoimmune diabetes of adults

2010 ◽  
Vol 163 (4) ◽  
pp. 541-549 ◽  
Author(s):  
M Maioli ◽  
G M Pes ◽  
G Delitala ◽  
L Puddu ◽  
A Falorni ◽  
...  
Keyword(s):  
Glutamic Acid ◽  
Disease Progression ◽  
Glutamic Acid Decarboxylase ◽  
Autoimmune Diabetes ◽  
Tyrosine Phosphatase ◽  
Female Gender ◽  
Acid Decarboxylase ◽  
Latent Autoimmune Diabetes ◽  
Insulin Dependence ◽  
Glutamic Acid Decarboxylase Autoantibodies

ObjectiveIn latent autoimmune diabetes of adults (LADA), the progression into insulin-dependent diabetes is usually faster than in type 2 diabetes (T2D) but the factors influencing this progression are not completely known. In this study, we searched for sensitive markers associated with early development of insulin dependence.DesignThe screening of 5568 T2D patients for glutamic acid decarboxylase autoantibodies (GAD65Ab) identified 276 LADA patients (M=131; F=145) and in 251 of them, tyrosine phosphatase-2 (IA-2Ab) and thyroperoxidase autoantibodies (TPOAbs), some clinical features and genotype variation of the main type 1 diabetes (T1D) disease susceptibility loci (HLA-DRB1 and HLA-DQB1) were analyzed.ResultsFour years after the diagnosis of diabetes, high GAD65Ab titer was not significantly associated with faster progression toward insulin deficiency (P=0.104). Patients with GAD65Ab and TPOAb or IA-2Ab or triple positivity for both islet and TPOAbs (GAD65Ab/IA-2Ab/TPOAb) showed a significantly faster disease progression (P=0.002). Among 104 TPOAb-positive LADA patients, 10 received replacement therapy (l-thyroxine), 43 showed high TSH levels (62.7% developed insulin dependence), and 3 had hyperthyroidism treated with methimazole. Multivariate analysis revealed a significant effect on disease progression only for TPOAb (P=0.022), female gender (P=0.036), low body mass index (BMI; P=0.001), and T1D high/intermediate risk HLA-DRB1/DQB1 genotypes grouped (P=0.020).ConclusionsHigh GAD65Ab titers per se are not a major risk factor for disease progression in LADA, while the number of positive autoantibodies and HLA DRB1-DQB1 genotypes at high risk for T1D are significant predictors. Moreover, clinical characteristics such as low BMI and female gender are more likely to identify patients who will require insulin therapy within 4 years of diagnosis.

scholarly journals Organ-specific and non-organ-specific autoantibodies in children and young adults with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)

2000 ◽  
pp. 497-503 ◽  
Author(s):  
R Perniola ◽  
A Falorni ◽  
MG Clemente ◽  
F Forini ◽  
E Accogli ◽  
...  
Keyword(s):  
Islet Cells ◽  
Tyrosine Phosphatase ◽  
Intrinsic Factor ◽  
Addison’S Disease ◽  
The Other ◽  
Acid Decarboxylase ◽  
Addison's Disease ◽  
Cyp Enzymes ◽  
Autoimmune Polyendocrinopathy ◽  
Organ Specific

OBJECTIVE: The aim of the study was to assess the complex of autoantibodies which can be detected in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a rare autosomal recessive disease in which the extent of autoimmunity is still unknown. DESIGN: Antibodies (A) to parathyroid glands, adrenal cortex (AC-A), ovary and testis (steroid cell antibodies, SC-A), pancreatic islet cells (IC-A), gastric parietal cells, and non-organ-specific antigens were investigated in 11 APECED patients living in the Salento region of southern Italy. Further measurements included antibodies to cytochrome P450 (CYP) enzymes: cholesterol side-chain cleavage enzyme (CYP11A), 21-hydroxylase (CYP21) and 17alpha-hydroxylase (CYP17); and to glutamic acid decarboxylase 65-kDa isoform (GAD65), tyrosine phosphatase-like protein IA2, thyroglobulin (TG), thyroperoxidase (TPO), thyrotropin receptor, liver CYP enzymes and intrinsic factor. METHODS: Antibodies to organs and subcellular fractions were detected by immunofluorescence. Radiobinding, immunoradiometric, and immunoblotting assays were used for the other measurements. RESULTS: AC-A and SC-A were positive in all sera; among antibodies to adrenal CYP enzymes, only CYP21-A were present in all the patients with Addison's disease of short-medium duration (<15 years). Of three patients with Addison's disease of long duration (>15 years), two tested positive for antibodies to all three CYP enzymes, and the other for only CYP11A-A. In all sera CYP11A-A and/or CYP17-A were found. Two patients tested positive for both IC-A and GAD65-A, one for both IC-A and IA2-A, and one for GAD65-A; the fasting C-peptide assay showed no statistical difference between these four subjects and the others. All four hypothyroid patients were positive for TPO-A, while two of them were positive and two were negative for TG-A; two euthyroid subjects had positivity for TG-A. Liver-kidney microsomal antibodies reacting against the CYP2A6 were detected in two patients with autoimmune hepatitis. All but one sera contained anti-nuclear antibodies at a titre ranging between 1:20 and 1:80; however, only two patients had a connective tissue disease (Sjogren's syndrome). CONCLUSIONS: Several autoantibodies may be detected in any APECED patient. Our data confirm that CYP21-A and TPO-A are major autoantibodies involved in APECED-associated Addison's disease and hypothyroidism respectively, while CYP11A-A and CYP17-A correlate with positivity for SC-A. Markers of islet cell autoimmunity are frequent, but prevalence and modalities of progression to overt beta-cell failure have to be clarified. Low-titre non-organ-specific autoantibodies are a feature of autoimmunity in APECED, but their role has yet to be fully explained.

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