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Actual condition survey regarding mismatch of measurements between radioimmunoassay and enzyme-linked immunosorbent assay tests for anti-glutamic acid decarboxylase antibody in real-world clinical practice.

ABSTRACT: Anti-glutamic acid decarboxylase antibody (GADA) is an important islet cell-associated autoantibody for the diagnosis of autoimmune type 1 diabetes mellitus. In Japan, the GADA assay kit was recently changed from radioimmunoassay (RIA) to enzyme-linked immunosorbent assay (ELISA). Thereafter, a mismatched measurement between the two tests became apparent in clinical situations. The present study aimed to clarify the actual extent of mismatch between the two measurements on a larger-scale real-world clinical practice. In this cross-sectional non-local/non-hospital-based study, we collected anonymized data on GADA levels of 598 participants, who were simultaneously measured with GADA-RIA and GADA enzyme-linked immunosorbent assay tests. We found that 34% of the GADA-RIA-positive participants showed negative results in the GADA enzyme-linked immunosorbent assay test; the mismatch was predominantly observed in participants with relatively low GADA-RIA levels (<32 U/mL). This considerable mismatch might lead to physicians' confusion in diagnosing type 1 diabetes mellitus.

SUBMITTER: Oikawa Y

PROVIDER: S-EPMC6497777 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Actual condition survey regarding mismatch of measurements between radioimmunoassay and enzyme-linked immunosorbent assay tests for anti-glutamic acid decarboxylase antibody in real-world clinical practice.

Oikawa Yoichi Y Kondo Takuma T Shimada Akira A Seino Yutaka Y Kitaoka Masafumi M

Journal of diabetes investigation 20181102 3

Anti-glutamic acid decarboxylase antibody (GADA) is an important islet cell-associated autoantibody for the diagnosis of autoimmune type 1 diabetes mellitus. In Japan, the GADA assay kit was recently changed from radioimmunoassay (RIA) to enzyme-linked immunosorbent assay (ELISA). Thereafter, a mismatched measurement between the two tests became apparent in clinical situations. The present study aimed to clarify the actual extent of mismatch between the two measurements on a larger-scale real-wo ...[more]

PMID: 30307126

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Project description:ImportanceLittle is known of glutamic acid decarboxylase antibodies (GAD-abs) in the paraneoplastic context. Clinical recognition of such cases will lead to prompt tumor diagnosis and appropriate treatment.ObjectiveTo report the clinical and immunological features of patients with paraneoplastic neurological syndromes (PNS) and GAD-abs.Design, setting, and participantsRetrospective case series study and immunological investigations conducted in February 2014 in a center for autoimmune neurological disorders. Fifteen cases with GAD65-abs evaluated between 1995 and 2013 who fulfilled criteria of definite or possible PNS without concomitant onconeural antibodies were included in this study.Main outcomes and measuresAnalysis of the clinical records of 15 patients and review of 19 previously reported cases. Indirect immunofluorescence with rat hippocampal neuronal cultures and cell-based assays with known neuronal cell-surface antigens were used. One hundred six patients with GAD65-abs and no cancer served as control individuals.ResultsEight of the 15 patients with cancer presented as classic paraneoplastic syndromes (5 limbic encephalitis, 1 paraneoplastic encephalomyelitis, 1 paraneoplastic cerebellar degeneration, and 1 opsoclonus-myoclonus syndrome). When compared with the 106 non-PNS cases, those with PNS were older (median age, 60 years vs 48 years; P = .03), more frequently male (60% vs 13%; P < .001), and had more often coexisting neuronal cell-surface antibodies, mainly against γ-aminobutyric acid receptors (53% vs 11%; P < .001). The tumors more frequently involved were lung (n = 6) and thymic neoplasms (n = 4). The risk for an underlying tumor was higher if the presentation was a classic PNS, if it was different from stiff-person syndrome or cerebellar ataxia (odds ratio, 10.5; 95% CI, 3.2-34.5), or if the patient had coexisting neuronal cell-surface antibodies (odds ratio, 6.8; 95% CI, 1.1-40.5). Compared with the current series, the 19 previously reported cases had more frequent stiff-person syndrome (74% vs 13%; P = .001) and better responses to treatment (79% vs 27%; P = .005). Predictors of improvement in the 34 patients (current and previously reported) included presentation with stiff-person syndrome and the presence of a thymic tumor.Conclusions and relevancePatients with GAD-abs must be screened for an underlying cancer if they have clinical presentations different from those typically associated with this autoimmunity or develop classic PNS. The risk for cancer increases with age, male sex, and the presence of coexisting neuronal cell-surface antibodies.

Project description:IMPORTANCE:High titers of autoantibodies to glutamic acid decarboxylase (GAD) are well documented in association with stiff person syndrome (SPS). Glutamic acid decarboxylase is the rate-limiting enzyme in the synthesis of ?-aminobutyric acid (GABA), and impaired function of GABAergic neurons has been implicated in the pathogenesis of SPS. Autoantibodies to GAD might be the causative agent or a disease marker. OBJECTIVE:To investigate the characteristics and potential pathogenicity of GAD autoantibodies in patients with SPS and related disorders. DESIGN:Retrospective cohort study and laboratory investigation. SETTING:Weatherall Institute of Molecular Medicine, University of Oxford. PARTICIPANTS:Twenty-five patients with SPS and related conditions identified from the Neuroimmunology Service. EXPOSURES:Neurological examination, serological characterization and experimental studies. MAIN OUTCOMES AND MEASURES:Characterization of serum GAD antibodies from patients with SPS and evidence for potential pathogenicity. RESULTS:We detected GAD autoantibodies at a very high titer (median, 7500 U/mL) in 19 patients (76%), including all 12 patients with classic SPS. The GAD autoantibodies were high affinity (antibody dissociation constant, 0.06-0.78 nmol) and predominantly IgG1 subclass. The patients’ autoantibodies co-localized with GAD on immunohistochemistry and in permeabilized cultured cerebellar GABAergic neurons, as expected, but they also bound to the cell surface of unpermeabilized GABAergic neurons. Adsorption of the highest titer (700 000 U/mL) serum with recombinant GAD indicated that these neuronal surface antibodies were not directed against GAD itself. Although intraperitoneal injection of IgG purified from the 2 available GAD autoantibody–ositive purified IgG preparations did not produce clinical or pathological evidence of disease, SPS and control IgG were detected in specific regions of the mouse central nervous system, particularly around the lateral and fourth ventricles. CONCLUSIONS AND RELEVANCE:Autoantibodies to GAD are associated with antibodies that bind to the surface of GABAergic neurons and that could be pathogenic. Moreover, in mice, human IgG from the periphery gained access to relevant areas in the hippocampus and brainstem. Identification of the target of the non-GAD antibodies and peripheral and intrathecal transfer protocols, combined with adsorption studies, should be used to demonstrate the role of the non-GAD IgG in SPS.

Dataset Information

Actual condition survey regarding mismatch of measurements between radioimmunoassay and enzyme-linked immunosorbent assay tests for anti-glutamic acid decarboxylase antibody in real-world clinical practice.

Publications

Actual condition survey regarding mismatch of measurements between radioimmunoassay and enzyme-linked immunosorbent assay tests for anti-glutamic acid decarboxylase antibody in real-world clinical practice.

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