To compare specificity and sensitivity of a commercially available fixed cell-based assay (F-CBA) to radioimmunoprecipitation assay (RIPA) for acetylcholine receptor antibody (anti-AChR) detection in myasthenia gravis (MG). Methods: In this retrospective diagnostic cohort study we reviewed the clinical information of suspected MG patients evaluated at the London Health Sciences Centre MG clinic who had anti-AChR RIPA and then F-CBA performed, in order to classify them as MG or non-MG. Classification of each patient as anti-AChR F-CBAnegative/positive, RIPA-negative/positive, and MG/non-MG permitted specificity and sensitivity calculations for each assay. Results: Six-hundred-eighteen patients were included in study analysis. The median patient age at time of sample collection was 45.8 years (range: 7.5-87.5 years) and 312/618 (50.5%) were female. Of 618 patients, 395 (63.9%) were classified as MG. Specificity of both F-CBA and RIPA was excellent (99.6% vs. 100%, P > 0.99). One F-CBA-positive patient was classified as non-MG, although in retrospect ocular MG with functional overlay was challenging to exclude. Sensitivity of F-CBA was significantly higher than RIPA (76.7% vs. 72.7%, P = 0.002). Overall, 20/97 (21%) otherwise seronegative MG (SNMG) patients after RIPA evaluation had anti-AChR detected by F-CBA. Conclusions: In our study anti-AChR F-CBA and RIPA both had excellent specificity, while F-CBA had 4% higher sensitivity for MG and detected anti-AChR in 21% of SNMG patients. Our findings indicate that F-CBA is a viable alternative to RIPA for anti-AChR detection. Prospective studies comparing F-CBA, RIPA and L-CBA are needed to determine optimal anti-AChR testing algorithms in MG.

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Neural antibodies have emerged as useful biomarkers in suspected autoimmune encephalitis. We reviewed results of neural antibody testing (anti-N-methyl D-aspartate receptor (NMDAR), leucine-rich glioma-inactivated protein (LGI1), contactin-associated protein-like 2 (CASPR2), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), γ-aminobutyric acid type B receptor (GABA(B)R), dipeptidyl-peptidase-like protein-6 (DPPX), IgLON family member 5 (IgLON5) and glutamic acid decarboxylase-65 (GAD65)) using cell-based assays (CBAs) and tissue indirect immunofluorescence (TIIF) at our centre. Our findings suggest increased clinical sensitivity of CBA compared to TIIF. However, this may come at some expense to clinical specificity, as evidenced by possible false-positive results when weak serum positivity by CBA was observed for certain antibodies (i.e. anti-NMDAR, CASPR2). In such cases, correlation with serum TIIF, as well as CSF CBA and TIIF, aids in identifying true-positive results.

Objectives Testing for renin and aldosterone in clinical laboratories is complicated by pre-analytical considerations such as the posture for blood collection and susceptibility to cryoactivation of renin. From an analytical perspective, there are both renin activity and renin mass or concentration assays available. There can also be variability in result reporting practices and the aldosterone-renin ratio (ARR) cut-off applied to screen for primary aldosteronism (PA). The Institute for Quality Management in Healthcare (IQMH) Centre for Proficiency Testing surveyed laboratories on their handling of renin and aldosterone testing to better understand current practices. Design and methods An online survey was prepared and sent to 134 Canadian laboratories enrolled in endocrinology proficiency testing with IQMH. Results One hundred twenty Ontario laboratories submitted responses. While only six (5%) laboratories perform testing for both renin and aldosterone, 108 (90%) collect and process specimens to be tested by reference laboratories. The survey revealed considerable variation in practices including the recommended state of patients prior to sample collection (for example, regarding medications or salt intake), the patient posture specifications for sample collection, the precautions taken against cryoactivation of renin, the choice of renin activity or mass assay, and the ARR cut-off used. The available literature on these factors was then reviewed. Conclusions Although there is no standardized procedure for specimen collection, analysis, or result reporting for renin or aldosterone testing, we have attempted to summarize the available literature to develop evidence-based recommendations. Where laboratory practice differs from peers and/or recommended protocols, laboratories should review their practices.