Caveats and Pitfalls of SOX1 Autoantibody Testing With a Commercial Line Blot Assay in Paraneoplastic Neurological Investigations

Ruiz‐García, Raquel; Martínez‐Hernández, Eugenia; García-Ormaechea, Milagros; Español-Rego, Marta; Sabater, Lidia; Querol, Luís; Illa, Isabel; Dalmau, Josep; Graus, Francesc

doi:10.3389/fimmu.2019.00769

Cited by 27 publications

(30 citation statements)

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“…However, very little is known about the reliability of these immunodot assays, as only a few published studies have analyzed the sensitivity for the detection of anti-CV2/CRMP5 (collapsin response-mediator protein-5) antibodies, 4 and the sensitivity and specificity for anti-Ma2 antibodies, 5 and anti-SOX1 antibodies. 6 In our laboratory, we use commercial immunodot assays as the first step of biological PNS diagnosis for all onconeural antibodies. Herein, we studied the diagnostic yield of 2 commercial immunodots by investigating the proportion of positive results confirmed by alternative techniques, taking also into account the clinical information when it was available.…”

mentioning

confidence: 99%

Diagnostic yield of commercial immunodots to diagnose paraneoplastic neurologic syndromes

Déchelotte

Muñiz‐Castrillo

Joubert

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo investigate the diagnostic yield of commercial immunodots to detect onconeural antibodies associated with paraneoplastic neurologic syndromes (PNSs), we analyzed the proportion of confirmed positive results using alternative techniques.MethodsSera (n = 5,300) of patients with suspected PNS were tested by PNS+2 blot (Ravo Diagnostika; January 2016–May 2017) or EUROLINE PNS 12 Ag (Euroimmun; July 2017–November 2018). Positive samples were further explored by in-house indirect immunofluorescence and a third in-house technique (Western blot or cell-based assay) using recombinant protein. Those found negative by these 2 techniques were considered as nonconfirmed. We analyzed the relationship between band intensity and final confirmation. Clinical data were collected for all confirmed results and nonconfirmed EUROLINE immunodots.ResultsPNS+2 blot was positive in 128/1,658 (7.7%) sera and confirmed in 47/128 (36.7%). EUROLINE was positive in 186/3,626 (5.1%) and confirmed in 56/186 (30.1%). Confirmation was highly variable among the antibodies tested, from 7.2% (PNS+2 blot) and 5.8% (EUROLINE) for anti-Yo to 88.2% (PNS+2 blot) and 65.0% (EUROLINE) for anti-Hu. None of the 27 weak positive sera by EUROLINE was confirmed. Band intensity in confirmed cases was variable among the antibodies from strong positive for all anti-Yo (n = 3) and anti-Hu (n = 11) to positive (n = 19) or strong positive (n = 9) for anti-SOX1. Among patients with a nonconfirmed EUROLINE result and available clinical information, all had an alternative diagnosis, and only 6.7% had cancer.ConclusionsImmunodots may be useful for PNS screening, but a threshold should be established for each antibody, and clinical information and confirmation by other techniques are essential.Classification of evidenceThe study provides Class IV evidence that immunodot assays for onconeural antibodies accurately identify patients with paraneoplastic neurologic syndromes.

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confidence: 99%

Diagnostic yield of commercial immunodots to diagnose paraneoplastic neurologic syndromes

Déchelotte

Muñiz‐Castrillo

Joubert

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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“…7,11,15,47 We presume that there were still some patients with LEMS and SCLC among the 30.9% of anti-SOX1 abs patients with unidentified PNS, based on most of them having SCLC. 12,48 Therefore, the actual proportion of patients with LEMS and anti-SOX1 abs should exceed 30.0%. Our review data support the notion that anti-SOX1 abs could be the main predictor of SCLC in patients with LEMS.…”

Section: Neurological Disordermentioning

confidence: 99%

“…11 Aside from LEMS, PCD, PLE, and neuropathy have also been reported. 12 However, the prevalence rates of these clinical symptoms and other clinical features in patients with anti-SOX1 abs still need to be systematically elucidated.…”

Section: Introductionmentioning

confidence: 99%

“…16 However, the understanding of the underlying mechanism of non-SCLC (NSCLC)-associated PNS is hindered by the rarity of the cases, with only a few studies described NSCLC patients presenting with anti-SOX1 abs. 12,[17][18][19][20][21] Since PCD is considered the most common PNS, we reviewed the neuronal autoabs and associated tumors present-ing as PCD (Table 1). In addition, we critically reviewed the clinical features of 486 cases of anti-SOX1 abs with identified tumors in 32 English-language and 4 Chinese-language studies reported up to December 2019 (Tables 2 and 3).…”

Section: Introductionmentioning

confidence: 99%

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Anti-SOX1 Antibodies in Paraneoplastic Neurological Syndrome

et al. 2020

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Anti-Sry-like high mobility group box (SOX) 1 antibodies (abs) are partly characterized onconeural autoantibodies (autoabs) due to their correlation with neoplastic diseases. Anti-SOX1 abs are associated with various clinical manifestations, including Lambert-Eaton myasthenic syndrome (LEMS) and paraneoplastic cerebellar degeneration (PCD). However, the clinical characteristics of patients with anti-SOX1 abs have not been described in detail. This review systematically explores the reported patients with anti-SOX1 abs and analyzes these cases for demographic characteristics, clinical features, coexisting neuronal autoabs, neuroimaging findings, treatment, and clinical outcomes. In addition, considering that PCD is the most common paraneoplastic neurological syndrome and that the association between PCD and anti-SOX1 abs remains unclear, we focus on the presence of autoabs in relation to PCD and associated tumors. PCD-associated autoabs include various intracellular autoabs (e.g., anti-Hu, anti-Yo, anti-Ri, and anti-SOX1) and cell-surface autoabs (anti-P/Q-type voltage-gated calcium channel). Commonly involved tumors in PCD are small-cell lung cancer (SCLC), gynecological, and breast tumors. LEMS is the most common clinical symptom in patients with anti-SOX1 abs, followed by PCD, and multiple neuronal autoabs coexist in 47.1% of these patients. SCLC is still the predominant tumor in patients with anti-SOX1 abs, while non-SCLC is uncommon. No consistent imaging feature is found in patients with anti-SOX1 abs, and there is no consensus on either the therapy choice or therapeutic efficacy. In conclusion, the presence of anti-SOX1 abs alone is a potential predictor of an uncommon paraneoplastic neurological disorder, usually occurring in the setting of LEMS, PCD, and SCLC. The detection of anti-SOX1 abs contributes to an early diagnosis of underlying tumors, given the diversity of clinical symptoms and the absence of characteristic neuroimaging features.

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“…Although blots can be more sensitive than TBA in rare cases (48), their use without TBAs can lead to false positive results, and is therefore discouraged (4,49,50). Inhouse CBAs have been used with selected antigens, such as CV2 and SOX1, showing a higher sensitivity compared to commercial blots (51,52). GAD antibodies can be quantified using ELISAs, RIAs, and luciferase immunoprecipitation system (LIPS) (47,53), which are more sensitive than TBAs and line/dot blots (4).…”

Section: Intracellular Neuronal Antibodiesmentioning

confidence: 99%

Autoantibody Diagnostics in Neuroimmunology: Experience From the 2018 Italian Neuroimmunology Association External Quality Assessment Program

et al. 2020

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Results: Three-quarter of the tests were commercial. Median accuracy for the laboratories was 75% (range 50-100). In 8/10 schemes, at least one sample provided discrepant results. Inter-laboratory "substantial agreement" was found in 6/10 schemes (AChR, MuSK, MAG, AQP4, MOG, and NS-Abs), whereas the worst agreements regarded OCBs and ganglioside-Abs. Both commercial and in-house assays performed better in experienced laboratories.Conclusions: Assays could be divided in (a) robust commercial tests with substantial inter-laboratory agreement (MAG-Abs; AChR-and MuSK-Abs); commercial/"in-house" tests with (b) partial inter-laboratory agreement (AQP4-Abs, MOG-Abs, NS-Abs, Gastaldi et al.AINI 2018 EQA Program ICN-Abs), and (c) with large inter-laboratory disagreement (OCBs, ganglioside-Abs). This real-life snapshot of the neuroimmunology test performances highlights shortcomings attributable to technician-dependent performances, assay structural limitations, and errors in test interpretations.

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Caveats and Pitfalls of SOX1 Autoantibody Testing With a Commercial Line Blot Assay in Paraneoplastic Neurological Investigations

Cited by 27 publications

References 15 publications

Diagnostic yield of commercial immunodots to diagnose paraneoplastic neurologic syndromes

Diagnostic yield of commercial immunodots to diagnose paraneoplastic neurologic syndromes

Anti-SOX1 Antibodies in Paraneoplastic Neurological Syndrome

Autoantibody Diagnostics in Neuroimmunology: Experience From the 2018 Italian Neuroimmunology Association External Quality Assessment Program

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