Cell-based assays for the detection of MOG antibodies: a comparative study

被引：47

作者：

Gastaldi, Matteo ^{[1
,2
]}

Scaranzin, Silvia ^{[1
]}

Jarius, Sven ^{[3
]}

Wildeman, Brigitte ^{[3
]}

Zardini, Elisabetta ^{[1
]}

Mallucci, Giulia ^{[4
]}

Rigoni, Eleonora ^{[4
]}

Vegezzi, Elisa ^{[2
]}

Foiadelli, Thomas ^{[5
]}

Savasta, Salvatore ^{[5
]}

Banfi, Paola ^{[6
]}

Versino, Maurizio ^{[6
]}

Benedetti, Luana ^{[7
]}

Novi, Giovanni ^{[7
,8
]}

Mancardi, Margherita Maria ^{[9
]}

Giacomini, Thea ^{[9
]}

Annovazzi, Pietro ^{[10
]}

Baroncini, Damiano ^{[10
]}

Ferraro, Diana ^{[11
]}

Lampasona, Vito ^{[12
]}

Reindl, Markus ^{[13
]}

Waters, Patrick ^{[14
]}

Franciotta, Diego ^{[1
]}

机构：

[1] IRCCS Mondino Fdn, Neuroimmunol Lab, Pavia, Italy

[2] IRCCS Mondino Fdn, Neurooncol & Neuroinflammat Unit, Pavia, Italy

[3] Heidelberg Univ, Otto Meyerhof Ctr, Dept Neurol, Mol Neuroimmunol Grp, Heidelberg, Germany

[4] IRCCS Mondino Fdn, Multiple Sclerosis Ctr, Pavia, Italy

[5] Univ Pavia, IRCCS Policlin San Matteo, Pediat Clin, Pavia, Italy

[6] Univ Insubria, Circolo Hosp, Neurol & Stroke Unit, Macchi Fdn, Varese, Italy

[7] Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, Genoa, Italy

[8] IRCCS Policlin San Martino, Genoa, Italy

[9] IRCCS Ist Giannina Gaslini, Unit Child Neuropsychiat, Clin & Surg Neurosci Dept, Genoa, Italy

[10] ASST Valle Olona Gallarate Hosp, Multiple Sclerosis Ctr, Gallarate, Italy

[11] Univ Modena & Reggio Emilia, Dept Biomed Metab & Neurosci, Modena, Italy

[12] IRCCS San Raffaele Hosp, San Raffaele Diabet Res Inst, Milan, Italy

[13] Med Univ Innsbruck, Clin Dept Neurol, Innsbruck, Austria

[14] Univ Oxford, Nuffield Dept Clin Neurosci, Autoimmune Neurol Grp, Oxford, England

来源：

JOURNAL OF NEUROLOGY | 2020年 / 267卷 / 12期

关键词：

Myelin oligodendrocyte glycoprotein; Autoantibodies; Cell-based assay; Demyelinating disorders; Standardization; Myelitis; Optic neuritis; Multiple sclerosis; MYELIN-OLIGODENDROCYTE GLYCOPROTEIN; MULTIPLE-SCLEROSIS; CLINICAL SPECTRUM; ANTIMYELIN ANTIBODIES; DISEASE; ADULTS; AUTOIMMUNITY; ASSOCIATION; SPECIFICITY; RESPONSES;

D O I：

10.1007/s00415-020-10024-0

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background The detection of antibodies to myelin oligodendrocyte glycoprotein (MOG) is fundamental for the identification of MOG antibody-associated disorders (MOGAD), and the differential diagnosis of acquired demyelinating syndromes of the CNS, among which multiple sclerosis (MS). We compared the diagnostic performance of four cell-based assays (CBAs) for their detection. Methods Consecutive sera from 204 patients with 'possible MOGAD' (55), MS (112), and other neurological disorders (OND, 37) were tested for MOG-IgG with a live-CBA with anti-heavy-and-light chain secondary-antibody (LCBA-IgG(H+L)), and a live-CBA for IgG(1)(LCBA-IgG(1)). A subgroup of 71 patients was additionally tested with a live-CBA with anti-Fc gamma secondary-antibody (LCBA-IgG(Fc gamma)), and a commercial fixed-CBA with anti-Fc gamma secondary-antibody (FCBA-IgG(Fc gamma))(.) Results Fifty-seven/204 patients (27.9%) were MOG-IgG-positive. Sensitivity was 89.1% (CI:77.8-95.9) and specificity 93.3% (CI:88.0-96.7) for LCBA-IgG(H+L), and 74.6% (CI:61.0-85.3) and 100% (CI:97.6-100) for LCBA-IgG(1). Eighteen of 57 (31%) samples showed discrepant results (all negative on LCBA-IgG(1)); of these, three with 'possible MOGAD' showed high-titer MOG-IgG (>= 1:640), and positivity for MOG-IgG(2), whereas 15/18 had low-titer MOG-IgG (1:160/1:320) and mixed diagnoses (5 'possible MOGAD', 6 MS, 4 OND). In the subgroup analysis, sensitivity was 92.3% (CI:79.1-98.4) and specificity 97.0% (CI:83.8-99.9) for LCBA-IgG(Fc gamma), and 87.2% (CI:72.6-95.7) and 97.0% (CI:83.8-99.9) for FCBA-IgG(Fc gamma). Conclusions LCBA-IgG(1)showed the highest specificity but can miss MOG-IgG(2)reactivities, whose meaning warrants further investigations. Titration of samples tested with LCBA-IgG(H+L)/ IgG(Fc gamma)is important for meaningful interpretation of the results. In the subgroup analysis, LCBA-IgG(Fc gamma)yielded the highest accuracy, and FCBA-IgG(Fc gamma)good specificity, but it was at risk of false-negative results.

引用

页码：3555 / 3564

页数：10

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