Measurement Of Autoantibodies Research Articles

7007 Analytical & Clinical Performance of a Novel Sensitive Rapid Bioassay for Thyrotropin Receptor Antibodies

Abstract Disclosure: P.D. Olivo: Consulting Fee; Self; QuidelOrtho, CA USA. H. Kim: Employee; Self; QuidelOrtho. L. Miao: Employee; Self; QuidelOrtho. J. Houtz: Employee; Self; QuidelOrtho. M. Luffy: None. J. Wolf: None. G.J. Kahaly: Grant Recipient; Self; QuidelOrtho, USA. Background: The role of stimulatory anti-TSH-R-Ab in the pathogenesis of autoimmune hyperthyroidism is well established. A novel and rapid cell-based bioassay, referred to as Turbo TSITM, for measurement of thyroid-stimulating autoantibodies (TSAb) was recently developed. An assessment of the analytical & clinical performance of this bioassay is described herein. Methods: Turbo TSI greatly reduces the complexity and time required to measure TSAb. It avoids the need for cell culture, has no wash or lysis steps, and has a total turn-around-time of less than 90 minutes. Thawed cells from Turbo TSI kits were treated with different concentrations of a World Health Organization (WHO) international standard (IS) TSI or TSAb-positive serum. TSAb was measured as a function of luciferase activity measured as relative light units (RLU) and converted into international units per liter (IU/L). Two users at two sites performed analytical performance studies on numerous samples, over multiple days. Results: The limit of blank, limit of detection and limit of quantitation were determined to be 0.007 IU/L, 0.014 IU/L, and 0.021 IU/L, respectively. Receiver operator characteristics (ROC) analysis determined the cut-off to be 0.0241 IU/L with an area under the curve of 0.984. The linear range was shown to be from 0.015 to 11.958 IU/L. The intra-laboratory precision was ≤15 percent CV. The overall reproducibility of the assay was ≤20 percent CV for five concentrations (0.06 to 5.16 IU/L). Interference and cross reactivity studies with a variety of substances showed that the assay was robust. Turbo TSI demonstrated 95.2% (95% CI 83.3-98.1) sensitivity and 94.8% (95% CI 90.9-97.1) specificity when compared with an FDA-cleared bioassay (Thyretain® TSI) using serum from 295 patients with autoimmune thyroid disease (AITD). When testing 172 unselected, consecutive TSAb+ AITD patients, a US based, prospective, multicenter, blinded study showed a 98% concordance between Turbo TSI and Thyretain® TSI. When comparing Turbo TSI, Thyretain TSI and a TSH-R-Ab binding immunoassay (Cobas) in 670 unselected, consecutive, treated and untreated AITD subjects, sensitivity was 83%, 79% and 68%, respectively (Turbo vs. Cobas, P<0.001). Furthermore, testing 84 patients with naïve, untreated Graves’ hyperthyroidism, detection of TSH-R-Ab was 100%, 98% and 92%, respectively (Turbo TSI vs binding assay, P<0.01). Finally, 95% vs. 73% of 332 patients with Graves’ orbitopathy were TSH-R-Ab+ with Turbo TSI vs. binding assay (P<0.001). Conclusions: The Turbo TSI bioassay exhibits excellent analytical & clinical performance, a high level of reproducibility, and compares well with the FDA-cleared Thyretain® TSI. Presentation: 6/1/2024

Enhanced Differentiation of Amiodarone-Induced Thyrotoxicosis Types Using Semi-Quantitative 99mTc-MIBI Uptake Analysis: A Pilot Study.

BACKGROUND Technetium (99mTc)-labelled Methoxy-2-Isobutylisonitrile (MIBI) is a diagnostic lipophilic cationic radiotracer used to evaluate the cardiac, breast, thyroid, and parathyroid pathology. This study aimed to evaluate the role of MIBI combined with Tc-99m pertechnetate thyroid scintigraphy, thyroid ultrasonography, and measurement of thyrotropin, thyroid hormones, and autoantibodies to subtype amiodarone-induced thyrotoxicosis (AIT) and the contribution of semi-quantitative analysis of MIBI uptake. MATERIAL AND METHODS This cross-sectional study included 36 patients with AIT who underwent thyrotropin, thyroid hormone, and autoantibody analysis using chemiluminescent method, ultrasonography, pertechnetate, and MIBI thyroid scintigraphy with semi-quantitative uptake, including calculation of the target-to-background ratio (TBR) with 2 different background regions. The MIBI washout rate (WR) was analyzed in all groups. Statistical analysis was performed using descriptive statistics, correlations, and the receiver operating characteristic curve - area under the curve (ROC-AUC). The results were compared with the control group. RESULTS Based on visual and semi-quantitative analyses, patients were successfully categorized into AIT groups (AIT-1, AIT-2 and AIT-3) but the latter method enabled better differentiation of MIBI uptake between all groups. Additionally, ROC-AUC analysis determined cutoff values which enabled discerning between AIT-1 and AIT-2 groups, and AIT-1 and AIT-3 groups. WR showed no significant difference between all AIT groups and controls (P>0.05). CONCLUSIONS Visual MIBI analysis enabled differentiation between AIT-1 and 2 groups, but the method was substantially improved with semi-quantitative analysis, especially in defining AIT-3 group. However, multicenter collaboration with larger studies is needed to standardize the method and obtain more accurate and consistent results.

A child with recurrent headache, fever and diffuse meningeal enhancement on MRI.

Juvenile neurolupus presents primarily with neuropsychiatric manifestations which may also be the initial presentation. Such primary neuropsychiatric SLE (NPSLE) events are a consequence either of microvasculopathy and thrombosis, or of autoantibodies and inflammatory mediators. Diagnosis of NPSLE requires the exclusion of other causes, and clinical assessment directs the selection of appropriate investigations. These investigations include measurement of autoantibodies, analysis of cerebrospinal fluid, electrophysiological studies, neuropsychological assessment and neuroimaging to evaluate brain structure and function. In our patient, the disease presented with chronic headache initially diagnosed as migraine, followed by fever and paraparesis. Fundoscopy showed retinal haemorrhages. Investigations revealed anaemia, neutrophilic leucocytosis, thrombocytopenia and raised inflammatory markers (ESR 119mm/h CRP 58mg/L) and high globulin. MRI brain showed diffuse meningeal enhancement resembling meningitis but CSF analysis was normal. ANA and dsDNA were positive with low C3, C4. All diffuse meningeal enhancements may not be meningitis and one needs to corroborate all the clinical, biochemical and imaging analyses to come to a diagnosis.

Altered Elastin Turnover, Immune Response, and Age-Related Retinal Thinning in a Transgenic Mouse Model With RPE-Specific HTRA1 Overexpression.

A single-nucleotide polymorphism in HTRA1 has been linked to age-related macular degeneration (AMD). Here we investigated the potential links between age-related retinal changes, elastin turnover, elastin autoantibody production, and complement C3 deposition in a mouse model with RPE-specific human HTRA1 overexpression. HTRA1 transgenic mice and age-matched CD1 wild-type mice were analyzed at 6 weeks and 4, 6, and 12 to 14months of age using in vivo retinal imaging by optical coherence tomography (OCT) and fundus photography, as well as molecular readouts, focusing on elastin and elastin-derived peptide quantification, antielastin autoantibody, and total Ig antibody measurements and immunohistochemistry to examine elastin, IgG, and C3 protein levels in retinal sections. OCT imaging indicated thinning of inner nuclear layer as an early phenotype in HTRA1 mice, followed by age and age/genotype-related thinning of the photoreceptor layer, RPE, and total retina. HTRA1 mice exhibited reduced elastin protein levels in the RPE/choroid and increased elastin breakdown products in the retina and serum. A corresponding age-dependent increase of serum antielastin IgG and IgM autoantibodies and total Ig antibody levels was observed. In the RPE/choroid, these changes were associated with an age-related increase of IgG and C3 deposition. Our results confirm that RPE-specific overexpression of human HTRA1 induces certain AMD-like phenotypes in mice. This includes altered elastin turnover, immune response, and complement deposition in the RPE/choroid in addition to age-related outer retinal and photoreceptor layer thinning. The identification of elastin-derived peptides and corresponding antielastin autoantibodies, together with increased C3 deposition in the RPE/choroid, provides a rationale for an overactive complement system in AMD irrespective of the underlying genetic risk.

Autoantibody-positivity before and seroconversion during treatment with anti-PD-1 is associated with immune-related adverse events in patients with melanoma

IntroductionTreatment with the immune checkpoint inhibitor anti-programmed cell death protein-1 (PD-1) often causes immune-related adverse events (irAEs). Since irAEs resemble autoimmune diseases, autoantibodies might play a role and could potentially...

An easy assay to detect autoantibodies neutralizing cytokines in subjects with critical infections

Autoantibodies against type I interferon (IFN) are associated with a worse outcome in COVID-19. The measurement of cytokine-neutralizing autoantibodies has been limited, hindering understanding of their role in clinical practice. We showed that an easy and reliable assay can be reproduced and validated to measure the neutralizing potency of autoantibodies directed to type I or type II IFN. Identifying of anti-cytokine autoantibodies might reflect on early treatments for subsequent infections, such as with antivirals or virus-neutralizing monoclonal antibodies.

How to Perform Autoantibody Testing for Autoimmune and Inflammatory Diseases of Peripheral Nerves and Muscles

Measurement of autoantibodies is essential for the management of several peripheral nerve and muscle diseases. The clinical significance of autoantibody testing differs for each antibody. In addition, clinicians must understand several issues including the accuracy of the test, isotype and subclass distribution, and its relationship to disease activity. Moreover, many autoantibody tests are not covered by health insurance. With limited medical resources, clinicians are required to be up-to-date with the latest information to utilize test results in daily practice without misunderstanding.

Immune-Mediated Necrotizing Myopathy

Immune-mediated necrotizing myopathy (IMNM) is a form of autoimmune myositis characterized by the presence of necrotic and regenerating process as a major finding in the muscle. Anti-SRP and anti-HMGCR have been identified as IMNM-specific autoantibodies. Patients with this disease often present with severe muscle weakness and markedly elevated serum creatine kinase (CK) levels. Differentiation from muscular dystrophy is challenging in certain cases. When patients meet the condition "subacute onset", "hyperCKemia over 1000 IU/L", and "clinical diagnosis of muscular dystrophy lacking molecular diagnosis", the possibility of IMNM should be considered. Autoantibody measurement, including of anti-SRP and HMGCR antibodies, is recommended. Treatment with corticosteroid in combination with immunosuppressants, intravenous immunoglobulin, and rituximab can be performed.

Autoimmune Nodopathy

Autoimmune nodopathy (AN), a newly established category of autoimmune disease, refers to an immune-mediated neuropathy associated with development of autoantibodies against membrane proteins, including neurofascin 186, neurofascin 155, contactin-1, and contactin-associated protein 1 located in the nodes of Ranvier or paranodes. Subclass analysis of these autoantibodies reveals predominant elevation of immunoglobulin (G4. Patients with AN show clinical and laboratory characteristics such as distal-predominant sensorimotor disturbance, sensory ataxia, poor response to intravenous immunoglobulin, and highly elevated cerebrospinal fluid protein levels. B cell-depletion therapy using an anti-CD20 monoclonal antibody is effective for patients with AN. Autoantibody measurement is beneficial not only for diagnosis but also for deciding treatment strategies for AN.

The effect of closed-loop glucose control on C-peptide secretion in youth with newly diagnosed type 1 diabetes: the CLOuD RCT

Background We assessed whether a sustained period of intensive glucose control with hybrid closed-loop for 12 months following diagnosis of type 1 diabetes in children and adolescents can preserve C-peptide secretion compared to standard insulin therapy. Methods In an open-label, multicentre, randomised, parallel trial, youth aged 10–16.9 years were randomised within 21 days of type 1 diabetes diagnosis to hybrid closed-loop or standard insulin therapy (control). Primary end point was the difference in mixed-meal C-peptide area under the curve 12 months post diagnosis. Key secondary end points included time spent in target glucose range, glycated haemoglobin and time spent below target glucose range at 12 months. Analysis was by intention to treat. The Closed Loop from Onset in Type 1 Diabetes consortium secured external funding for participants to continue on beyond 12 months, but the funding by National Institute for Health and Care Research and the results reported here refer only to the 12 months follow-up. Results We randomised 97 participants (mean ± standard deviation age 12 ± 2 years), 51 to closed-loop and 46 to control therapy. There was no difference in C-peptide area under the curve at 12 months between groups [geometric mean (interquartile range) closed-loop (n = 46): 0.35 pmol/ml (0.16, 0.49) vs. control (n = 37): 0.46 pmol/ml (0.22, 0.69); mean adjusted difference –0.06 (95% confidence interval –0.14 to 0.03); p = 0.19]. The proportion of time in target range 3.9–10.0 mmol/l based on 14-day masked LibrePro (Abbott Diabetes Care, Maidenhead, UK) sensor glucose data at 12 months was 10 percentage points (95% confidence interval 2 to 17) higher in the closed-loop group (64 ± 14%) compared to control group (54 ± 23%). Arithmetic mean glycated haemoglobin A1c was lower in the closed-loop group by 4 mmol/mol (0.4%) [95% confidence interval 0 to 8 mmol/mol (0.0% to 0.7%)] at 12 months. The mean difference in time spent < 3.9 mmol/l between groups was 0.9 percentage points (95% confidence interval –1.0 to 2.8). Three severe hypoglycaemic events occurred in the closed-loop group (two participants), and one in the control group; one diabetic ketoacidosis occurred in the closed-loop group. Conclusions A sustained period of hybrid closed-loop glucose control following diagnosis of type 1 diabetes in children and adolescents does not slow down the decline in residual C-peptide secretion compared with standard insulin therapy. Despite the lack of effect on C-peptide, glycaemic control was sustained in the closed-loop group, whereas glycaemic control deteriorated in the control group 6 to 9 months after diagnosis and closed-loop safely accommodated the variability in exogenous insulin requirements which occur with beta-cell recovery post diagnosis. Limitations of the study included no central measurement of auto-antibodies at diagnosis. There was imbalance in the rate of diabetic ketoacidosis at diagnosis which is associated with a more rapid decline in C-peptide secretion, but this was adjusted for in the analyses. This highlights the need for improved therapies to allow youth to achieve recommended glycaemic targets from onset of type 1 diabetes irrespective of the lack of effect on residual C-peptide secretion. Future work includes ongoing follow-up of the study population for up to 4 years after diagnosis to observe how any differences in glycaemic control between treatment groups develop over time. Trial registration This trial is registered as Clinicaltrials.gov NCT02871089. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 14/23/09), the Helmsley Trust (2016PG-T1D045 and 2016PG-T1D046), and JDRF (22-2013-266 and 2-RSC-2019-828-M-N), and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 8. See the NIHR Funding and Awards website for further award information. Additional support for the artificial pancreas work was from the NIHR Cambridge Biomedical Research Centre and NIHR Oxford Biomedical Research Centre. Abbott Diabetes Care supplied free glucose monitoring devices, and Dexcom supplied discounted continuous glucose monitoring devices. Medtronic supplied discounted insulin pumps, phone enclosures, continuous glucose monitoring devices, and pump consumables.

Primary Sjögren’s syndrome: Autoantibodies and their relationship to clinical manifestations and histology of minor salivary glands

Introduction/ObjectiveTo evaluate the association between autoantibodies with clinical manifestations (extraglandular and glandular) and histopathological findings of minor salivary gland biopsy in primary Sjögren’s syndrome. Materials and methodsObservational, descriptive, and cross-sectional study. Forty-seven patients with pSS according to the ACR/EULAR 2016 criteria were included. A face-to-face survey, a review of medical records, and the measurement of autoantibodies (Ab) anti-Ro 52, anti-Ro 60, anti-La, antinuclear antibodies (ANA), rheumatoid factor (RF) IgA, IgG and IgM, and anti-alpha fodrin IgA and IgG were done. Characterization of the population and analysis of the association between clinical characteristics, autoantibodies, and histopathology were performed. ResultsAssociation of anti-alpha fodrin IgA and anti-Ro 52 Ab was found with pulmonary involvement (P = .014 and P = .031 respectively) and anti-La antibodies with haematological manifestations, specifically leukopenia (P = .011), lymphopenia (P = .023), and anaemia (P = .09). We found no association between the histopathological findings of the minor salivary gland biopsy and extraglandular manifestations. ConclusionsThe activation of B cells, reflected in the increased production of autoantibodies, is related to extraglandular manifestations in pSS, which is observed more frequently in patients with earlier diagnosis.

Improved Specificity of Glutamate Decarboxylase 65 Autoantibody Measurement Using Luciferase-Based Immunoprecipitation System Assays.

Autoantibodies to glutamate decarboxylase (GADA) are widely used in the prediction and classification of type 1 diabetes. GADA radiobinding assays (RBAs) using N-terminally truncated antigens offer improved specificity but radioisotopes limit the high-throughput potential for population screening. Luciferase-based Immunoprecipitation System (LIPS) assays are sensitive and specific alternatives to RBAs with the potential to improve risk stratification. The performance of assays using the Luciferase (Nluc-) conjugated GAD65 constructs, Nluc-GAD65(96-585) and full length Nluc-GAD65(1-585) were evaluated in 434 well-characterised sera from recent-onset type 1 diabetes patients and first-degree relatives. Non-radioactive, high-throughput LIPS assays are quicker and require less serum than RBAs. Of 171 relatives previously tested single autoantibody positive for autoantibodies to full-length GAD65 by RBA but had not progressed to diabetes, fewer retested positive by LIPS using either truncated (n=72) or full-length (n=111) antigen. The Nluc-GAD65(96-585) truncation demonstrated the highest specificity in LIPS assays overall but in contrast to RBA, N-terminus truncations did not result in a significant increase in disease-specificity compared with the full-length antigen. This suggests that binding of non-specific antibodies is affected by the conformational changes resulting from addition of the Nluc antigen. Nluc-GAD65(96-585) LIPS assays offer low blood volume, high specificity GADA tests for screening and diagnostics.

Autoantibodies Serum Level and 10-Year Risk of Fractures Evaluated by FRAX® Tool in Rheumatoid Arthritis Patients.

FRAX® is a tool used for evaluation of risk of fracture in RA and non-RA patients and to identify those eligible for intervention. One of the limitations of FRAX in RA settings is that it does not consider factors known to contribute to osteoporosis such as autoantibodies. This study analysed the association of anti-mutated citrullinated vimentin antibody (anti-MCV), anti-cyclic citrullinated peptide antibody (anti-CCP), IgM rheumatoid factor (RF), IgA RF with 10-year risk of major osteoporosis and hip fracture. FRAX® tool was used to estimate 10-year risk of major osteoporosis fracture and hip fracture in 189 RA patients over 40 years of age. Anti-MCV, anti-CCP, IgM RF and IgA RF were tested using enzyme immunoassay and analysed at different levels. Results were adjusted for various confounders including disease activity. Fifty-one (26.9%) RA patients had high (≥20%) 10-year risk of major osteoporosis fracture and 67 (35.4%) had high (>3%) 10-year risk of hip fracture. Among all the tested autoantibodies, only IgM RF at elevated levels was associated with high 10-year risk of major osteoporosis fracture (adjusted OR = 4.1, 95% CI = 1.5-11.3, p = 0.006) and of hip fracture (adjusted OR = 17.4, 95% CI = 3.7-81.3, p < 0.0001). There was no agreement between FRAX and femoral neck (FN) BMD. None of the autoantibodies tested were associated with FN osteopenia or osteoporosis including IgM RF at high levels. Our study highlights the importance of quantitative measurement of autoantibodies in assessment of risk for fractures among RA patients. Our preliminary findings need to be assessed in prospective studies to determine the actual predictive value of high IgM RF levels among patients with RA.

Transdermal Blood Sampling for C-Peptide Is a Minimally Invasive, Reliable Alternative to Venous Sampling in Children and Adults With Type 1 Diabetes.

C-peptide and islet autoantibodies are key type 1 diabetes biomarkers, typically requiring venous sampling, which limits their utility. We assessed transdermal capillary blood (TCB) collection as a practical alternative. Ninety-one individuals (71 with type 1 diabetes, 20 control; individuals with type 1 diabetes: aged median 14.8 years [interquartile range (IQR) 9.1-17.1], diabetes duration 4.0 years [1.5-7.7]; control individuals: 42.2 years [38.0-52.1]) underwent contemporaneous venous and TCB sampling for measurement of plasma C-peptide. Participants with type 1 diabetes also provided venous serum and plasma, and TCB plasma for measurement of autoantibodies to glutamate decarboxylase, islet antigen-2, and zinc transporter 8. The ability of TCB plasma to detect significant endogenous insulin secretion (venous C-peptide ≥200 pmol/L) was compared along with agreement in levels, using Bland-Altman. Venous serum was compared with venous and TCB plasma for detection of autoantibodies, using established thresholds. Acceptability was assessed by age-appropriate questionnaire. Transdermal sampling took a mean of 2.35 min (SD 1.49). Median sample volume was 50 µL (IQR 40-50) with 3 of 91 (3.3%) failures, and 13 of 88 (14.7%) <35 µL. TCB C-peptide showed good agreement with venous plasma (mean venous ln[C-peptide] - TCB ln[C-peptide] = 0.008, 95% CI [-0.23, 0.29], with 100% [36 of 36] sensitivity/100% [50 of 50] specificity to detect venous C-peptide ≥200 pmol/L). Where venous serum in multiple autoantibody positive TCB plasma agreed in 22 of 32 (sensitivity 69%), comparative specificity was 35 of 36 (97%). TCB was preferred to venous sampling (type 1 diabetes: 63% vs. 7%; 30% undecided). Transdermal capillary testing for C-peptide is a sensitive, specific, and acceptable alternative to venous sampling; TCB sampling for islet autoantibodies needs further assessment.

Extremely Early Appearance of Islet Autoantibodies in Genetically Susceptible Children

Objective. We studied the characteristics of children who developed islet autoantibodies by the age of 0.50 years and hypothesized that the appearance of extremely early islet autoimmunity differs between four birth cohorts within 1994–2019 according to the change in the incidence of Type 1 diabetes (T1D) in Finland. Methods. Data from Finnish children participating in the Type 1 Diabetes Prediction and Prevention (DIPP) study, or the Environmental Determinants of Diabetes in the Young (TEDDY) study were analyzed. These studies follow children with increased HLA-conferred risk for T1D with regular measurements of islet autoantibodies. Maternally transferred antibodies were excluded by comparing islet autoantibodies in cord serum, child’s first follow-up serum and the maternal serum. Results. Among 20,979 Finnish children at increased risk to T1D, 53 (0.25%) developed at least one islet autoantibody at the age of ≤0.50 years. During a mean follow-up of 8.1 years, 15.1% progressed to T1D (median age at diagnosis 2.0 years), 43.4% developed confirmed islet autoimmunity but no T1D, and 41.5% had only transient islet autoantibodies. IAA was the most common first-appearing autoantibody. Among progressors, age at diagnosis was 1.0–2.4 years in children with IAA-initiated autoimmunity and 4.5–16.1 years in ZnT8A-initiated autoimmunity. When comparing children developing autoantibodies either at the age of ≤0.50 years or 0.51–0.75 years, confirmed positivity during follow-up was more common in the older group (81.7% vs. 58.5%; p = 0.002 ). In four birth cohorts within 1994–2019 appearance of islet autoantibodies at the age of ≤0.50 years decreased towards the most recent birth cohorts ( p = 0.016 ). Conclusion. Islet autoimmunity by the age of 0.50 years was rare in genetically susceptible children and was typically initiated with IAA. Confirmed positivity was less common in children with autoantibodies at age ≤0.50 than at slightly older age. The secular decrease of islet autoimmunity before age 0.50 years was observed. This trial is registered with NCT03269084 and NCT00279318.

Performance evaluation of the EUROIMMUN anti‐acetylcholine receptor enzyme‐linked immunoassay

AbstractObjectivesAnti‐acetylcholine receptor antibodies (AChR Ab) are one of the pathogenic autoantibodies in myasthenia gravis (MG), and they are specifically mentioned in the Japanese clinical guidelines for MG. In the serological diagnosis and measurement of autoantibodies as an adjunct marker for MG, the radioimmunoassay (RIA) method has been conventionally used as the gold standard. However, there have been several worldwide concerns regarding the use of radioisotopes. In this study, we evaluated the performance of the EUROIMMUN AChR Ab enzyme‐linked immunosorbent assay (ELISA) in comparison with RIA.MethodsELISA reproducibility and dilution linearity were analyzed using AChR Ab‐positive samples. Sera from 50 patients with suspected MG and 50 healthy donors were used to assess the correlation and qualitative agreement between the two methods.ResultsThe ELISA showed good interassay precision and dilution linearity. The correlation coefficient, sensitivity, specificity and overall agreement of the ELISA in comparison with the conventional RIA amounted to 0.87, 98%, 92% and 95% (kappa = 0.895), respectively. Analysis of the discordant results suggested that the ELISA might be more capable of detecting low AChR Ab reactivity in patients with suspected MG.ConclusionsThe AchR Ab ELISA provides a reliable tool for the quantification of AchR Ab, supporting the diagnosis of MG. As a non‐isotopic assay with good precision, shorter handling time and high correlation with the conventional RIA, the AChR ELISA could be a useful alternative in the laboratory routine.

One third of cases of new-onset diabetic ketosis in adults are associated with ketosis-prone type 2 diabetes-A systematic review and meta-analysis.

Ketosis-prone type 2 diabetes was defined by the World Health Organization in 2019. According to the literature, the diagnosis is based on the presence of ketosis, islet autoantibody negativity and preserved insulin secretion. Our meta-analysis assessed the prevalence and clinical characteristics of ketosis-prone type 2 diabetes among patients hospitalised with diabetic ketoacidosis (DKA) or ketosis. The systematic search was performed in five main databases as of 15 October 2021 without restrictions. We calculated the pooled prevalence of ketosis-prone type 2 diabetes (exposed group) within the diabetic population under examination, patients with ketoacidosis or ketosis, to identify the clinical characteristics, and we compared it to type 1 diabetes (the comparator group). The random effects model provided pooled estimates as prevalence, odds ratio and mean difference (MD) with 95% confidence intervals. Eleven articles were eligible for meta-analysis, thus incorporating 2010 patients of various ethnic backgrounds. Among patients presenting with DKA or ketosis at the onset of diabetes, 35% (95% CI: 24%-49%) had ketosis-prone type 2 diabetes. These patients were older (MD=11.55years; 95% CI: 5.5-17.6) and had a significantly higher body mass index (BMI) (MD=5.48kg/m2 ; 95% CI: 3.25-7.72) than those with type 1 diabetes. Ketosis-prone type 2 diabetes accounts for one third of DKA or ketosis at the onset of diabetes in adults. These patients are characterised by islet autoantibody negativity and preserved insulin secretion. They are older and have a higher BMI compared with type 1 diabetes. C-peptide and diabetes-related autoantibody measurement is essential to identify this subgroup among patients with ketosis at the onset of diabetes.

Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus.

Numerous laboratory tests are used in the diagnosis and management of diabetes mellitus. The quality of the scientific evidence supporting the use of these assays varies substantially. An expert committee compiled evidence-based recommendations for laboratory analysis in screening, diagnosis, or monitoring of diabetes. The overall quality of the evidence and the strength of the recommendations were evaluated. The draft consensus recommendations were evaluated by invited reviewers and presented for public comment. Suggestions were incorporated as deemed appropriate by the authors (see Acknowledgments). The guidelines were reviewed by the Evidence Based Laboratory Medicine Committee and the Board of Directors of the American Association of Clinical Chemistry and by the Professional Practice Committee of the American Diabetes Association. Diabetes can be diagnosed by demonstrating increased concentrations of glucose in venous plasma or increased hemoglobin A1c (Hb A1c) in the blood. Glycemic control is monitored by the people with diabetes measuring their own blood glucose with meters and/or with continuous interstitial glucose monitoring (CGM) devices and also by laboratory analysis of Hb A1c. The potential roles of noninvasive glucose monitoring, genetic testing, and measurement of ketones, autoantibodies, urine albumin, insulin, proinsulin, and C-peptide are addressed. The guidelines provide specific recommendations based on published data or derived from expert consensus. Several analytes are found to have minimal clinical value at the present time, and measurement of them is not recommended.

Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus.

Numerous laboratory tests are used in the diagnosis and management of diabetes mellitus. The quality of the scientific evidence supporting the use of these assays varies substantially. An expert committee compiled evidence-based recommendations for laboratory analysis in screening, diagnosis, or monitoring of diabetes. The overall quality of the evidence and the strength of the recommendations were evaluated. The draft consensus recommendations were evaluated by invited reviewers and presented for public comment. Suggestions were incorporated as deemed appropriate by the authors (see Acknowledgments). The guidelines were reviewed by the Evidence Based Laboratory Medicine Committee and the Board of Directors of the American Association for Clinical Chemistry and by the Professional Practice Committee of the American Diabetes Association. Diabetes can be diagnosed by demonstrating increased concentrations of glucose in venous plasma or increased hemoglobin A1c (HbA1c) in the blood. Glycemic control is monitored by the people with diabetes measuring their own blood glucose with meters and/or with continuous interstitial glucose monitoring (CGM) devices and also by laboratory analysis of HbA1c. The potential roles of noninvasive glucose monitoring, genetic testing, and measurement of ketones, autoantibodies, urine albumin, insulin, proinsulin, and C-peptide are addressed. The guidelines provide specific recommendations based on published data or derived from expert consensus. Several analytes are found to have minimal clinical value at the present time, and measurement of them is not recommended.

Executive Summary: Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus.

Numerous laboratory tests are used in the diagnosis and management of patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these assays varies substantially. An expert committee compiled evidence-based recommendations for laboratory analysis in patients with diabetes. The overall quality of the evidence and the strength of the recommendations were evaluated. The draft consensus recommendations were evaluated by invited reviewers and presented for public comment. Suggestions were incorporated as deemed appropriate by the authors (see Acknowledgments in the full version of the guideline). The guidelines were reviewed by the Evidence Based Laboratory Medicine Committee and the Board of Directors of the American Association for Clinical Chemistry and by the Professional Practice Committee of the American Diabetes Association. Diabetes can be diagnosed by demonstrating increased concentrations of glucose in venous plasma or increased hemoglobin A1c (HbA1c) in the blood. Glycemic control is monitored by the patients measuring their own blood glucose with meters and/or with continuous interstitial glucose monitoring devices and also by laboratory analysis of HbA1c. The potential roles of noninvasive glucose monitoring; genetic testing; and measurement of ketones, autoantibodies, urine albumin, insulin, proinsulin, and C-peptide are addressed. The guidelines provide specific recommendations based on published data or derived from expert consensus. Several analytes are found to have minimal clinical value at the present time, and measurement of them is not recommended.