المؤلفون: Laura Pyle, Peter A. Gottlieb, Taylor M. Triolo, Andrea K. Steck, Liping Yu

المصدر: Diabetes. 69

مصطلحات موضوعية: endocrine system, Allergy, medicine.medical_specialty, Type 1 diabetes, business.industry, Endocrinology, Diabetes and Metabolism, Haplotype, Autoantibody, Human leukocyte antigen, medicine.disease, Diabetes mellitus, Internal medicine, Genotype, Internal Medicine, Medicine, Radiobinding assay, business

الوصف: Electrochemiluminescence (ECL) assays are high-affinity autoantibodies (Abs) that are more specific than radiobinding assay (RBA) Abs for the prediction of type 1 diabetes (T1D) in natural history studies screening for risk and progression to T1D. We analyzed 603 subjects from the TrialNet Pathway to Prevention Study who were positive for at least one RBA diabetes related Ab and for whom ECL and HLA data were available. We sought to characterize ECL-GADA and ECL-IAA positivity and levels (z-scores) by HLA genotype and haplotypes. Mean age at initial visit was 19.4 ± 13.7 years; 345 (57.2%) were female and 104 (17.2%) carried the high-risk HLA- DR3/4*0302 genotype. At initial visit 425 (70%) of subjects were positive for either ECL-GADA or ECL-IAA, with 207 (34.3%) ECL-IAA positive subjects and 367 (60.9%) ECL-GADA positive subjects. For subjects with high-risk HLA-DR3/4 genotype (n=104), 80 (76.9%) were positive for ECL-GADA, while 42 (40.4%) were positive for ECL-IAA. ECL and RBA-GADA z-scores were higher in subjects with HLA-DR3 haplotypes, while ECL-IAA (but not RBA-IAA) z-scores were associated with HLA-DR4 haplotypes. Associations of ECL and RIA Abs with high-risk HLA haplotypes are shown in the Table. In conclusion, ECL and RBA-GADA positivity are associated with both HLA-DR3 and DR4 haplotypes, whereas only ECL-IAA (but not RBA-IAA) positivity and levels are associated with HLA-DR4 haplotype. Disclosure T.M. Triolo: None. L. Pyle: None. L. Yu: None. P. Gottlieb: Advisory Panel; Self; Janssen Scientific Affairs, LLC., Tolerion, Inc., Viacyte, Inc. Research Support; Self; Caladrius Biosciences, Inc., Immune Tolerance Network, Janssen Pharmaceuticals, Inc., JDRF, Leona M. and Harry B. Helmsley Charitable Trust, Mercia/Nova Laboratories, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk Inc. Stock/Shareholder; Self; IM Therapeutics. A. Steck: None. Funding American Diabetes Association (1-14-CD-17 to A.S.); National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development; JDRF

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::21e35a8289d867fa1f8dd88c3853928dTest
https://doi.org/10.2337/db20-1617-pTest

المؤلفون: Polly J. Bingley, Cristina Brigatti, Vito Lampasona, Alistair J K Williams, Kathleen M Gillespie, Rebecca Wyatt, Peter Achenbach

المصدر: Diabetes 64, 3247-3252 (2015)

مصطلحات موضوعية: Adult, Male, endocrine system, Diabetes risk, Adolescent, Endocrinology, Diabetes and Metabolism, Sensitivity and Specificity, Young Adult, Diabetes mellitus, Internal Medicine, medicine, Humans, Family, In patient, Child, Autoantibodies, Type 1 diabetes, Glutamate Decarboxylase, business.industry, Autoantibody, Infant, Middle Aged, medicine.disease, Clinical disease, Peptide Fragments, Diabetes Mellitus, Type 1, Increased risk, Child, Preschool, Immunology, Disease Progression, Female, Radiobinding assay, business

الوصف: GAD autoantibodies (GADAs) identify individuals at increased risk of developing type 1 diabetes, but many people currently found to be GADA positive are unlikely to progress to clinical disease. More specific GADA assays are therefore needed. Recent international workshops have shown that the reactivity of sera from healthy donors varies according to assay type and indicated that the use of N-terminally truncated GAD65 radiolabels in GADA radiobinding assays is associated with higher specificity. To determine whether a radiobinding assay using radiolabeled GAD65(96–585) identified individuals who are at higher risk of developing diabetes, samples from recent-onset patients and GADA-positive first-degree relatives participating in the Bart’s-Oxford type 1 diabetes family study were reassayed with full-length or N-terminally truncated GAD using the National Institute of Diabetes and Digestive and Kidney Diseases harmonized protocol. The sensitivity in patients was the same with both labels, but fewer relatives retested positive with truncated GAD. Among relatives who progressed to diabetes, similar proportions were found to be GADA positive when tested with either label, but because of their higher specificity the cumulative risk of diabetes was higher in those with autoantibodies to GAD65(96–585). Autoantibodies to GAD65(96–585) in relatives are more closely associated with diabetes risk than those to full-length GAD, suggesting that assays using N-terminally truncated GAD should be used to select participants for intervention trials.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b58360d7f63d4291dbf795fc0f118c8fTest
https://doi.org/10.2337/db14-1694Test

المؤلفون: Polly J. Bingley, Karen T Elvers, Deborah K. Shoemark, Ivey A. Geoghegan, Vito Lampasona, Alistair J K Williams

المصدر: Diabetes

مصطلحات موضوعية: Adult, Male, Adolescent, Endocrinology, Diabetes and Metabolism, Molecular Sequence Data, 030209 endocrinology & metabolism, Protein tyrosine phosphatase, Biology, Epitope, Structure-Activity Relationship, 03 medical and health sciences, 0302 clinical medicine, Protein structure, Internal Medicine, Humans, Receptor-Like Protein Tyrosine Phosphatases, Class 8, Amino Acid Sequence, Cysteine, Child, Autoantibodies, 030304 developmental biology, 0303 health sciences, Autoantibody, Antibodies, Monoclonal, Molecular biology, Protein Structure, Tertiary, 3. Good health, Diabetes Mellitus, Type 1, Epitope mapping, Biochemistry, Child, Preschool, Female, Radiobinding assay, Immunology and Transplantation, Epitope Mapping, Conformational epitope

الوصف: Cysteines are thought integral to conformational epitopes of islet antigen-2 (IA-2) autoantibodies (IA-2A), possibly through disulfide bond formation. We therefore investigated which cysteines are critical to IA-2A binding in patients with newly diagnosed type 1 diabetes. All 10 cysteines in the intracellular domain of IA-2 were modified to serine by site-directed mutagenesis, and the effects of these changes on autoantibody binding in comparison with wild-type control were investigated by radiobinding assay. Mutation of the protein tyrosine phosphatase (PTP) core cysteine (C909) in IA-2 caused large reductions in autoantibody binding. In contrast, little or no reduction in binding was seen following substitution of the other cysteines. Modification of the core cysteine (C945) in IA-2β also greatly reduced autoantibody binding. Lysine substitution of glutamate-836 in IA-2 or glutamate-872 in IA-2β resulted in modest reductions in binding and identified a second epitope region. Binding to IA-2 PTP and IA-2β PTP was almost abolished by mutation of both the core cysteine and these glutamates. The core cysteine is key to the major PTP conformational epitope, but disulfide bonding contributes little to IA-2A epitope integrity. In most patients, at disease onset, >90% of antibodies binding to the PTP domain of IA-2 recognize just two epitope regions.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7e2407457a3072b0aa6c8ac3c3fb527bTest
https://doi.org/10.2337/db11-1590Test

المؤلفون: David V. Serreze, Thomas W.H. Kay, Mark A. Atkinson, George S. Eisenbarth, Bhagirath Singh, Ezio Bonifacio, Edwin Lee-Chan

المصدر: Diabetes. 50:2451-2458

مصطلحات موضوعية: Autoimmune disease, medicine.medical_specialty, Type 1 diabetes, Endocrinology, Diabetes and Metabolism, Autoantibody, Nod, Biology, medicine.disease_cause, medicine.disease, Autoimmunity, Endocrinology, Diabetes mellitus, Internal medicine, Immunology, Internal Medicine, medicine, Radiobinding assay, NOD mice

الوصف: 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 (50%) at diabetes onset, with results concordant with those of RBA. Remarkably, GADA and IA-2A frequencies varied significantly with respect to the source colony of NOD mice. Furthermore, whereas neither GADA nor IA-2A correlated with IAA, there was strong concordance between GADA and IA-2A in individual mice. Sera with increased binding to GAD and IA-2 also had increased binding to the unrelated antigen myelin oligodendrocyte glycoprotein, and binding to GAD could not be inhibited with excess unlabeled antigen, suggesting nonspecific interactions. In sum, this workshop demonstrated that IAA measured by sensitive RBA are a marker of autoimmunity in NOD mice and draw into question the true nature of GADA and IA-2A in this animal model.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::601b730a6627d2c6569d7e501c2a76a5Test
https://doi.org/10.2337Test/diabetes.50.11.2451

المؤلفون: George S. Eisenbarth, Peter G. Colman, Charles F. Verge, D Stenger, P. J. Bingley, C Pilcher, Ezio Bonifacio

المصدر: Diabetes. 47:1857-1866

مصطلحات موضوعية: medicine.medical_specialty, Type 1 diabetes, medicine.diagnostic_test, biology, business.industry, Endocrinology, Diabetes and Metabolism, Insulin, medicine.medical_treatment, Autoantibody, Radioimmunoassay, medicine.disease, Endocrinology, Internal medicine, Immunoassay, Diabetes mellitus, Immunology, Internal Medicine, medicine, biology.protein, Radiobinding assay, Antibody, business

الوصف: The aim of this workshop was to assess the ability of individual autoantibody (ab) assays and their use in combination to discriminate between type 1 diabetic and control sera. Coded aliquots of sera were measured in a total of 119 assays by 49 participating laboratories in 17 countries. The sera were from 51 patients with new onset type 1 diabetes and 101 healthy control subjects with no family history of diabetes. In the final analysis, data on diabetic sera were restricted to 43 subjects younger than age 30 years. The laboratories were asked to report results for these sera using their currently available anti-islet autoantibody assays. In addition, they were asked to combine information from their assays to classify sera as having high, moderate, or low probability of originating from a patient with type 1 diabetes. Actual strategies for combining assays were determined by each laboratory. There were no significant differences in sensitivity among 19 radioimmunoassays (RIAs) for IA-2 autoantibodies (cytoplasmic islet cell antibody [ICA] 512) using different constructs that included the intracellular portion of the molecule (mean sensitivity 73%). However, an enzyme-linked immunosorbent assay (ELISA) using the extracellular portion of the IA-2 molecule did not discriminate between diabetic and control sera. Among GAD autoantibody assays that achieved sensitivity >70%, 26 were RIAs and one was an ELISA. When the sera were ranked according to their autoantibody levels, the concordance for insulin autoantibodies (IAAs) in different laboratories was markedly less than for IA-2ab and GADab. Using a combination of autoantibody assays, several laboratories achieved excellent discrimination between diabetic and control sera (sensitivity up to 80% with false-positive rate of 0%). A variety of strategies for combining information from different assays were successful (e.g., those including and excluding ICA), and no one strategy emerged as clearly superior. In conclusion, IA-2/ICA512 autoantibodies are a marker of type 1 diabetes and can be measured consistently by most assays. Several different strategies for combining assays achieved high sensitivity with a low false-positive rate.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::021d4871300fb5a556925bb50a37c8c8Test
https://doi.org/10.2337Test/diabetes.47.12.1857

المؤلفون: Massimo Pietropaolo, Richard A. Jackson, Charles F. Verge, H. P. Chase, Liping Yu, George S. Eisenbarth, Roberto Gianani, Eiji Kawasaki

المصدر: Diabetes. 45:926-933

مصطلحات موضوعية: Proband, Adult, Male, medicine.medical_specialty, Time Factors, Adolescent, Offspring, medicine.medical_treatment, Insulin Antibodies, Endocrinology, Diabetes and Metabolism, Mothers, Risk Assessment, Disease-Free Survival, Nuclear Family, Fathers, Predictive Value of Tests, Diabetes mellitus, Internal medicine, medicine, Internal Medicine, Humans, Risk factor, First-degree relatives, Child, Aged, Autoantibodies, Models, Genetic, business.industry, Glutamate Decarboxylase, Insulin, Autoantibody, Infant, Newborn, Infant, Middle Aged, medicine.disease, Endocrinology, Diabetes Mellitus, Type 1, Child, Preschool, Female, Radiobinding assay, business, Follow-Up Studies

الوصف: Islet cell antibodies (ICAs) are predictive of type I diabetes in first-degree relatives, but this immunohistochemical assay has proven difficult to standardize. As an alternative, we assessed the use of radioassays for antibodies against three molecularly characterized islet autoantigens, including ICA512bdc (amino acid residues 256–979 of the IA-2 molecule, incorporating the intracellular domain). We measured insulin autoantibodies (IAAs), GAD autoantibodies (GAAs), and ICA512bdc autoantibodies (ICA512bdcAAs) by radioassay, in addition to ICAs, in 882 first-degree relatives of patients with type I diabetes, 50 of whom later developed diabetes with a median follow-up of 2.0 years (maximum 11.3 years). The cutoff for each radioassay was determined by testing >200 control subjects. When autoantibody frequencies among the relatives were analyzed according to relationship to the proband, the offspring of diabetic fathers had a higher frequency of ICA512bdcAAs (P = 0.008), IAAs (P = 0.0001) and GAAs (P = 0.0001) than the offspring of diabetic mothers. ICA512bdcAAs and IAAs both showed a significant association with HLA-DR4-DQ8 (P = 0.0005). Among relatives developing diabetes, 98% had one or more of IAAs, GAAs, or ICA512bdcAAs, and 80% had two or more of these autoantibodies, compared with none of the control subjects. Using survival analysis to allow for different lengths of follow-up, there was a significant increase in the risk of diabetes with the number of these autoantibodies present, comparing zero, one, two, and three autoantibodies (P < 0.0001, log-rank test), and by Cox regression analysis, this was independent of ICAs and age. For relatives with two or more of these autoantibodies, the risk of diabetes within 3 years was 39% (95% CI, 27–52) and the risk within 5 years was 68% (95% CI, 52–84). Relatives with all three autoantibodies had a risk within 5 years estimated to be 100%. The presence of low first-phase insulin release further increased the risk for relatives with one or two autoantibodies. We conclude that the presence of two or more autoantibodies (out of IAAs, GAAs, and ICA512bdcAAs) is highly predictive of the development of type I diabetes among relatives.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4b092777f6c97ca5a816c41ba01ae986Test
https://doi.org/10.2337Test/diabetes.45.7.926

المؤلفون: Vito Lampasona, Ezio Bonifacio, Anette Gabriele Ziegler, Laura Bernasconi

المصدر: Diabetes. 49(2)

مصطلحات موضوعية: endocrine system, endocrine system diseases, Offspring, Endocrinology, Diabetes and Metabolism, Autoimmunity, Biology, medicine.disease_cause, Epitope, Cohort Studies, Epitopes, Child Development, immune system diseases, Internal Medicine, medicine, Humans, Child, Autoimmune disease, Glutamate Decarboxylase, Autoantibody, Antibody titer, nutritional and metabolic diseases, Infant, medicine.disease, Diabetes Mellitus, Type 1, Child, Preschool, Immunology, Antibody Formation, biology.protein, Disease Progression, Radiobinding assay, Antibody

الوصف: GAD is a major target of autoimmunity in preclinical type 1 diabetes. Here we examine the maturation of the humoral response to GAD epitopes sequentially from birth to diabetes onset or current follow-up in 29 GAD antibody (GADA)+ offspring of parents with diabetes from the BABYDIAB Study. Antibodies were measured against GAD65, GAD67, and GAD65/67 chimeras by radiobinding assay. In 28 of 29 offspring, the first GADAs contained reactivity against epitopes within GAD65 residues 96-444, suggesting that the middle GAD65 region is a primary target of GAD humoral autoimmunity. In 7 of these 28 offspring, initial antibody reactivity was against all epitope regions tested (middle GAD65, COOH-terminal GAD65 residues 445-585, NH2-terminal GAD65 residues 1-95, and GAD67); in 16 offspring, reactivity was to middle and COOH-terminal GAD65 epitopes, and in 5 offspring, reactivity was only to the middle GAD65 epitopes. The single offspring without middle GAD65 reactivity had antibodies to the NH2-terminal epitopes in the absence of all other islet autoimmunity. Subsequent GADA epitope spreading was frequent and seen in 10 of 15 offspring with informative follow-up samples. Spreading was mostly (eight cases) to NH2-terminal GAD65 epitopes. In two offspring, spreading to new epitopes was found when antibody titers to GAD65 and early epitopes were declining, suggesting determinant-specific regulation of the humoral response. None of the GADA reactivities nor any changes in reactivity over time were specifically associated with diabetes onset. The findings suggest that the humoral autoimmune response to GAD found in childhood is dynamic, is initially against epitopes within the middle portion of GAD65, and spreads to epitopes in other regions of GAD65 and GAD67.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2168cc7a59c555d31eda17a6a21d707aTest
https://pubmed.ncbi.nlm.nih.gov/10868936Test

المؤلفون: J Dittler, D Seidel, Anette-G. Ziegler, M Schenker

المصدر: Diabetes. 47(4)

مصطلحات موضوعية: Proband, Adult, Risk, medicine.medical_specialty, Diabetes risk, Adolescent, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Biology, Autoantigens, Sensitivity and Specificity, Islets of Langerhans, Radioligand Assay, Predictive Value of Tests, Internal medicine, Internal Medicine, medicine, Humans, Insulin, Family, Life Tables, Receptor-Like Protein Tyrosine Phosphatases, Class 8, Child, Aged, Autoantibodies, Protein Tyrosine Phosphatase, Non-Receptor Type 1, Type 1 diabetes, Glutamate Decarboxylase, Autoantibody, Infant, Membrane Proteins, Glucose Tolerance Test, Middle Aged, medicine.disease, Titer, Endocrinology, Diabetes Mellitus, Type 1, Child, Preschool, biology.protein, Radiobinding assay, Antibody, Protein Tyrosine Phosphatases, Biomarkers

الوصف: A new radiobinding assay for the simultaneous detection of antibodies to GAD and the tyrosine phosphatase IA2 has been recently described in patients with newly diagnosed type 1 diabetes. Here we assessed sensitivity and predictive value of this GADIA2-combi test in first-degree relatives of type 1 diabetic patients compared with islet cell antibody (ICA) and insulin autoantibody (IAA) screening. Of 1,606 relatives, 77 (4.8%) had elevated GADIA2-combi titers above the 99th percentile of 105 nondiabetic control subjects, and results were confirmed by testing these samples for GAD antibody (GADA) and tyrosine phosphatase IA2 antibody (IA2A) in the single antibody test (29 GADA+/IA2A+, 44 GADA+/IA2A-, and 4 IA2A+/GADA-). A further 9 of 1,606 relatives had detectable ICA (1) or IAA (8), but they were negative in the GADIA2-combi assay as well as in the single test for GADA or IA2A. Twenty-four relatives progressed to IDDM within a median follow-up time of 5.6 years (range 0.5-8.2). The sensitivity of antibody determination in relatives with progression to IDDM was 92% for the GADIA2-combi assay, 96% for the combined testing of IAA and GADIA2-combi antibodies, and 83, 67, 67, and 79%, respectively, for GADA, IA2A, IAA, or ICA testing alone. The cumulative life-table risk of antibody-positive relatives was related to GADIA2-combi titers (5-year risk: >50 U, 51% [95% CI 30-73]; >10 to 50 U, 12% [1-24]; 15 years) or relation to proband (offspring, sibling, parent). Relatives with GADIA2-combi antibodies >10 U and the additional presence of IAA had a slightly higher diabetes risk than relatives without IAA (5-year: IAA+, 46% [23-68]; IAA-, 19% [6-32]; P=0.07). Furthermore, low first-phase insulin release after intravenous glucose tolerance test was associated with risk in relatives with GADIA2-combi antibodies (P=0.01). These results indicate that the GADIA2-combi test is a valuable marker for first-line screening and risk assessment of type 1 diabetes in relatives. It can be used for venous as well as capillary blood samples.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1459318171e847e0a7d8cfe34a49d8ffTest
https://pubmed.ncbi.nlm.nih.gov/9568692Test

المؤلفون: Robert S. Schmidli, Peter G. Colman, Ezio Bonifacio

المصدر: Diabetes. 44(6)

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Serial dilution, Adolescent, medicine.drug_class, Endocrinology, Diabetes and Metabolism, Glutamate decarboxylase, Radioimmunoassay, Enzyme-Linked Immunosorbent Assay, Monoclonal antibody, Sensitivity and Specificity, Antibodies, Immunopathology, Internal medicine, Internal Medicine, medicine, Humans, Child, Aged, biology, business.industry, Glutamate Decarboxylase, Middle Aged, Precipitin, Precipitin Tests, Endocrinology, Diabetes Mellitus, Type 1, biology.protein, Female, Radiobinding assay, Antibody, business

الوصف: There is increasing interest in the use of glutamic acid decarboxylase antibodies (GADAbs) for identification of subjects at increased risk of developing insulin-dependent diabetes mellitus (IDDM). However, considerable variation exists between laboratories in the reported frequency of GADAb in various clinical situations, and disease sensitivity and specificity have not yet been compared between assays. An international workshop was held in which 101 coded freeze-dried sera, including 39 from subjects with newly diagnosed IDDM, 32 from healthy control subjects, 4 from nondiabetic subjects with Graves' disease, and 4 from islet cell antibody–positive subjects, were analyzed in 52 assays (radiobinding assay [RBA], 26; enzyme-linked immunosorbent assay [ELISA], 19; and enzymatic immunoprecipitation assay [EIP], 7). The mean sensitivity for RBAs (76.2%) was higher than for ELISAs (36.5%) and EIPs (49.9%) (P < 0.01). The mean specificity was similar for each assay format (RBA, 89.4%; ELISA. 89.4%; and EIP, 92.3%). The lower sensitivities of the ELISA and EIP were predominantly due to the inability of these assays to detect low levels of GADAb in IDDM. To convert results to standard units, standard curves were constructed using duplicate dilutions of the anti–glutamic acid decarboxylase monoclonal antibody MICA 3 and serum from a patient with stiff-man syndrome (SMS). Curves could be derived in 28 assays using the MICA 3 serum and in 29 using the SMS serum. The mean coefficients of variation between assays for disease and control samples were 45% when results were converted to MICA units, 77% for SMS units, and 76% for SD scores. The relatively lower scatter observed using the MICA 3 serum as a standard indicates that this serum may be useful as an international reference. Because assays for GADAb with a high level of sensitivity and specificity are now available, prospective studies are now required to establish the role of GADAbin clinical applications such as preclinical screening for IDDM.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ba98b5fd5fd33d23b1ec110ec8c095d7Test
https://pubmed.ncbi.nlm.nih.gov/7789627Test