94dcf4f11f85b783c318f703a9fa396b pmc_10116574.pdf 4294877455a6e4b068f45a0c634411c512c2e14d pmc_10116574.pdf 69206bcbd96bde058c57d8536054ab0a76ae0c289087faf29aa0404f6d6eca43 pmc_10116574.pdf Creator: Servigistics Arbortext Advanced Print Publisher 11.1.4546/W-x64 Producer: PDFlib+PDI 9.0.7p3 (C++/Win64) CreationDate: Tue Apr 18 05:01:23 2023 CEST ModDate: Tue Apr 18 05:01:23 2023 CEST Tagged: yes UserProperties: no Suspects: no Form: none JavaScript: no Pages: 10 Encrypted: no Page size: 612.283 x 790.866 pts Page rot: 0 File size: 1132727 bytes Optimized: yes PDF version: 1.6 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- OCUKSL+GillSansMTStd-Bold Type 1C Custom yes yes yes 690 0 WTMRKH+SabonLTStd-Roman Type 1C Custom yes yes yes 695 0 QWDYHL+SabonLTStd-Italic Type 1C Custom yes yes yes 700 0 VPNKAM+STIXGeneral-Regular Type 1C Custom yes yes yes 705 0 ONJLBL+GillSansMTStd-Medium Type 1C Custom yes yes yes 710 0 UWWKIV+GillSansMT Type 1 Custom yes yes no 718 0 ZYWMSZ+GillSansMTStd-MediumItalic Type 1C Custom yes yes yes 51 0 HIQHNG+GillSansMTStd-BoldItalic Type 1C Custom yes yes yes 12 0 ZLPTGA+STIXGeneral-Bold Type 1C Custom yes yes yes 17 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-08-04 02:29:26 CEST RepresentationInformation: pmc_10116574.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-08-01 02:34:52 CEST Size: 1132727 Format: PDF Version: 1.6 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf Profile: Linearized PDF, Tagged PDF PDFMetadata: Objects: 746 FreeObjects: 1 IncrementalUpdates: 1 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: false CenterWindow: false DisplayDocTitle: true NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: OneColumn PageMode: UseOutlines Language: en Outlines: Item: Title: Antibodies against the flotillin-1/2 complex in patients with multiple sclerosis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@11758f2a Children: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@e720b71 Item: Title: Materials and methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1b26f7b2 Children: Item: Title: Patients and protocol approvals Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@491cc5c9 Item: Title: Testing for anti-NF155 and anti-ANO2 antibodies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@74ad1f1f Item: Title: Testing for anti-FLOT-1/2 antibodies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6a1aab78 Item: Title: FLOT-1/2 and ANO2 immunoadsorption Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@462d5aee Item: Title: Statistical analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@69b0fd6f Item: Title: Data availability Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@757942a1 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4a87761d Children: Item: Title: Baseline characteristics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@66d1af89 Item: Title: Autoantibodies against NF155 and ANO2 Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@8646db9 Item: Title: Autoantibodies against the FLOT-1/2 complex Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@37374a5e Item: Title: Reactivity against FLOT-1/2 and ANO2 antibodies was abrogated after immunoadsorption Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4671e53b Item: Title: Clinical features Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@2db7a79b Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6950e31 Item: Title: Acknowledgements Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@b7dd107 Item: Title: Funding Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@42eca56e Item: Title: Competing interests Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@52f759d7 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7cbd213e Info: Creator: Servigistics Arbortext Advanced Print Publisher 11.1.4546/W-x64 Producer: PDFlib+PDI 9.0.7p3 (C++/Win64) CreationDate: Tue Apr 18 05:31:23 CEST 2023 ModDate: Tue Apr 18 05:31:23 CEST 2023 ID: 0x2e3b458f913aaaf4c1431a38fe71c229, 0x2e3b458f913aaaf4c1431a38fe71c229 Filters: FilterPipeline: FlateDecode FilterPipeline: DCTDecode Images: Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 1000 ImageHeight: 1113 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 1266 ImageHeight: 955 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 1000 ImageHeight: 753 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 1266 ImageHeight: 635 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 1266 ImageHeight: 1274 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Fonts: Type1: Font: BaseFont: VPNKAM+STIXGeneral-Regular FontSubset: true FirstChar: 1 LastChar: 7 FontDescriptor: FontName: VPNKAM+STIXGeneral-Regular Flags: Nonsymbolic FontBBox: -995, -455, 2000, 1055 FontFile3: true EncodingDictionary: BaseEncoding: WinAnsiEncoding Differences: true ToUnicode: true Font: BaseFont: ZLPTGA+STIXGeneral-Bold FontSubset: true FirstChar: 1 LastChar: 1 FontDescriptor: FontName: ZLPTGA+STIXGeneral-Bold Flags: Nonsymbolic, ForceBold FontBBox: -1030, -455, 2000, 1055 FontFile3: true EncodingDictionary: BaseEncoding: WinAnsiEncoding Differences: true ToUnicode: true Font: BaseFont: OCUKSL+GillSansMTStd-Bold FontSubset: true FirstChar: 1 LastChar: 73 FontDescriptor: FontName: OCUKSL+GillSansMTStd-Bold Flags: Nonsymbolic, ForceBold FontBBox: -177, -237, 1167, 957 FontFile3: true EncodingDictionary: BaseEncoding: WinAnsiEncoding Differences: true ToUnicode: true Font: BaseFont: ZYWMSZ+GillSansMTStd-MediumItalic FontSubset: true FirstChar: 1 LastChar: 7 FontDescriptor: FontName: ZYWMSZ+GillSansMTStd-MediumItalic Flags: Nonsymbolic, Italic FontBBox: -201, -233, 1009, 931 FontFile3: true EncodingDictionary: BaseEncoding: WinAnsiEncoding Differences: true ToUnicode: true Font: BaseFont: ONJLBL+GillSansMTStd-Medium FontSubset: true FirstChar: 2 LastChar: 71 FontDescriptor: FontName: ONJLBL+GillSansMTStd-Medium Flags: Nonsymbolic FontBBox: -162, -234, 1041, 931 FontFile3: true EncodingDictionary: BaseEncoding: WinAnsiEncoding Differences: true ToUnicode: true Font: BaseFont: WTMRKH+SabonLTStd-Roman FontSubset: true FirstChar: 1 LastChar: 94 FontDescriptor: FontName: WTMRKH+SabonLTStd-Roman Flags: Nonsymbolic FontBBox: -165, -228, 1000, 944 FontFile3: true EncodingDictionary: BaseEncoding: WinAnsiEncoding Differences: true ToUnicode: true Font: BaseFont: QWDYHL+SabonLTStd-Italic FontSubset: true FirstChar: 1 LastChar: 45 FontDescriptor: FontName: QWDYHL+SabonLTStd-Italic Flags: Nonsymbolic, Italic FontBBox: -146, -228, 1059, 927 FontFile3: true EncodingDictionary: BaseEncoding: WinAnsiEncoding Differences: true ToUnicode: true Font: BaseFont: HIQHNG+GillSansMTStd-BoldItalic FontSubset: true FirstChar: 1 LastChar: 2 FontDescriptor: FontName: HIQHNG+GillSansMTStd-BoldItalic Flags: Nonsymbolic, Italic, ForceBold FontBBox: -190, -237, 1074, 959 FontFile3: true EncodingDictionary: BaseEncoding: WinAnsiEncoding Differences: true ToUnicode: true XMP: uuid:573CE618-D38B-6855-FD0E-C52614F51B6E uuid:BF6F4FF5-28DD-579A-50B9-093C6597E3CB True autoantibodies; multiple sclerosis; antigens application/pdf 10.1093/braincomms/fcad109 en Oxford University Press Antibodies against the flotillin-1/2 complex in patients with multiple sclerosis Cinta Lleixà Marta Caballero-Ávila Elba Pascual-Goñi Lorena Martín-Aguilar Nuria Vidal Clara Tejada Eduardo Valdés-Hevia Elisa Zárate Ana Vesperinas Roger Collet Teresa Franco-Leyva Laura Martínez-Martínez Esther Moga Elena Cortés-Vicente Ricard Rojas-García Beatriz Gómez-Anson Anna Gil Cristina González-Mingot Luis Brieva Sergio Martínez-Yélamos Luis Querol DOI: 10.1093/braincomms/fcad109; Brain Communications, 5, 2, 2023-4-4.; Abstract: Multiple sclerosis is a tissue-specific autoimmune disease of the central nervous system in which the antigen(s) remains elusive. Antibodies targeting the flotillin-1/2 complex have been described in 1–2% of the patients in a recent study. Other candidate antigens as anoctamin-2 or neurofascin-155 have been previously described in multiple sclerosis patients, although their clinical relevance remains uncertain. Our study aims to analyse the frequency and clinical relevance of antibodies against neurofascin-155, anoctamin-2 and flotillin-1/2 complex in multiple sclerosis. Serum (n = 252) and CSF (n = 50) samples from 282 multiple sclerosis patients were included in the study. The control group was composed of 260 serum samples (71 healthy donors and 189 with other neuroinflammatory disorders). Anti-flotillin-1/2, anti-anoctamin-2 and anti-neurofascin-155 antibodies were tested by cell-based assays using transfected cells. We identified six multiple sclerosis patients with antibodies against the flotillin-1/2 complex (2.1%) and one multiple sclerosis patient with antibodies against anoctamin-2 (0.35%). All multiple sclerosis patients were negative for anti-neurofascin-155 antibodies. Three of the anti-flotillin-1/2 positive patients showed anti-flotillin-1/2 positivity in other serum samples extracted at different moments of their disease. Immunoglobulin G subclasses of anti-flotillin-1/2 antibodies were predominantly one and three. We confirm that antibodies targeting the flotillin-1/2 complex are present in a subgroup of patients with multiple sclerosis. Further studies are needed to understand the clinical and pathological relevance of anti-flotillin-1/2 autoantibodies in multiple sclerosis. autoantibodies multiple sclerosis antigens © The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. PDFlib+PDI 9.0.7p3 (C++/Win64) Journal Brain Communications © The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. 2632-1297 5 2 1 10 10.1093/braincomms/fcad109 https://doi.org/10.1093/braincomms/fcad109 PDF/UA Universal Accessibility Schema http://www.aiim.org/pdfua/ns/id/ pdfuaid part Integer internal Indicates, which part of ISO 14289 standard is followed 2023-04-18T08:31:23+05:30 2023-04-18T08:31:23+05:30 Servigistics Arbortext Advanced Print Publisher 11.1.4546/W-x64 2023-04-18T08:31:23+05:30 PStill version 1.84.42 Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 405, 583, 415, 593 Flags: Print Annotation: Subtype: Link Rect: 430, 569, 440, 579 Flags: Print Annotation: Subtype: Link Rect: 56, 555, 66, 565 Flags: Print Annotation: Subtype: Link Rect: 279, 555, 289, 565 Flags: Print Annotation: Subtype: Link Rect: 56, 527, 66, 537 Flags: Print Annotation: Subtype: Link Rect: 470, 527, 480, 537 Flags: Print Annotation: Subtype: Link Rect: 87, 121, 167, 130 Flags: Print Annotation: Subtype: Link Rect: 346, 49, 467, 55 Flags: Print Annotation: Subtype: Link Rect: 56, 750, 208, 759 Flags: Print Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 149, 92, 153, 102 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 152, 56, 156, 66 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 448, 152, 452, 162 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 475, 140, 478, 150 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 488, 128, 492, 138 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 551, 104, 555, 114 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 495, 80, 499, 90 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 500, 80, 504, 90 Flags: Print Destination: 43 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 282, 716, 286, 726 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 233, 704, 237, 714 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 150, 692, 158, 702 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 270, 692, 277, 702 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 159, 680, 167, 690 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 169, 680, 177, 690 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 110, 656, 118, 666 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 123, 632, 131, 642 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 132, 632, 140, 642 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 72, 456, 79, 465 Flags: Print Destination: 43 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 390, 652, 421, 661 Flags: Print Destination: 10 Annotation: Subtype: Link Rect: 344, 506, 367, 515 Flags: Print Destination: 24 Annotation: Subtype: Link Rect: 451, 336, 475, 345 Flags: Print Destination: 29 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 84, 208, 107, 218 Flags: Print Destination: 29 Annotation: Subtype: Link Rect: 527, 52, 547, 61 Flags: Print Destination: 34 Page: Sequence: 6 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 68, 52, 100, 61 Flags: Print Destination: 39 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 143, 392, 151, 402 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 283, 140, 291, 150 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 74, 68, 82, 78 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 547, 332, 555, 342 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 344, 296, 352, 306 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 476, 260, 484, 270 Flags: Print Destination: 47 Annotation: Subtype: Link Rect: 547, 224, 555, 234 Flags: Print Destination: 47 Annotation: Subtype: Link Rect: 410, 200, 417, 210 Flags: Print Destination: 47 Annotation: Subtype: Link Rect: 408, 152, 416, 162 Flags: Print Destination: 47 Annotation: Subtype: Link Rect: 407, 128, 415, 138 Flags: Print Destination: 47 Annotation: Subtype: Link Rect: 547, 68, 555, 78 Flags: Print Destination: 43 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 80, 716, 88, 726 Flags: Print Destination: 47 Annotation: Subtype: Link Rect: 145, 692, 153, 702 Flags: Print Destination: 47 Annotation: Subtype: Link Rect: 292, 620, 300, 630 Flags: Print Destination: 47 Annotation: Subtype: Link Rect: 207, 596, 215, 606 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 217, 596, 225, 606 Flags: Print Destination: 47 Annotation: Subtype: Link Rect: 170, 512, 178, 522 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 320, 645, 325, 653 Flags: Print Destination: 1 Annotation: Subtype: Link Rect: 320, 624, 325, 633 Flags: Print Destination: 1 Annotation: Subtype: Link Rect: 320, 614, 325, 622 Flags: Print Destination: 1 Annotation: Subtype: Link Rect: 320, 584, 325, 592 Flags: Print Destination: 1 Annotation: Subtype: Link Rect: 320, 554, 325, 562 Flags: Print Destination: 1 Annotation: Subtype: Link Rect: 320, 524, 325, 532 Flags: Print Destination: 1 Annotation: Subtype: Link Rect: 320, 494, 325, 502 Flags: Print Destination: 1 Annotation: Subtype: Link Rect: 320, 464, 325, 472 Flags: Print Destination: 1 Annotation: Subtype: Link Rect: 320, 444, 325, 452 Flags: Print Destination: 6 Annotation: Subtype: Link Rect: 320, 404, 329, 412 Flags: Print Destination: 6 Annotation: Subtype: Link Rect: 320, 374, 329, 381 Flags: Print Destination: 6 Annotation: Subtype: Link Rect: 320, 343, 329, 351 Flags: Print Destination: 6 Annotation: Subtype: Link Rect: 320, 313, 329, 321 Flags: Print Destination: 6 Annotation: Subtype: Link Rect: 320, 283, 329, 291 Flags: Print Destination: 6 Annotation: Subtype: Link Rect: 320, 253, 329, 261 Flags: Print Destination: 6 Annotation: Subtype: Link Rect: 320, 223, 329, 231 Flags: Print Destination: 6 Annotation: Subtype: Link Rect: 320, 183, 329, 191 Flags: Print Destination: 6 Annotation: Subtype: Link Rect: 320, 153, 329, 161 Flags: Print Destination: 39 Annotation: Subtype: Link Rect: 320, 123, 329, 131 Flags: Print Destination: 39 Annotation: Subtype: Link Rect: 320, 92, 329, 100 Flags: Print Destination: 39 Annotation: Subtype: Link Rect: 320, 72, 329, 80 Flags: Print Destination: 39 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 47, 725, 56, 733 Flags: Print Destination: 39 Annotation: Subtype: Link Rect: 47, 695, 56, 703 Flags: Print Destination: 39 Annotation: Subtype: Link Rect: 47, 665, 56, 673 Flags: Print Destination: 39 Annotation: Subtype: Link Rect: 47, 635, 56, 643 Flags: Print Destination: 39 Annotation: Subtype: Link Rect: 311, 725, 320, 733 Flags: Print Destination: 39 Annotation: Subtype: Link Rect: 311, 705, 320, 713 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 311, 675, 320, 683 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 311, 655, 320, 663 Flags: Print Destination: 43 Annotation: Subtype: Link Rect: 311, 635, 320, 643 Flags: Print Destination: 43 Checksum: 6568e68f Type: CRC32 Checksum: 94dcf4f11f85b783c318f703a9fa396b Type: MD5 Checksum: 4294877455a6e4b068f45a0c634411c512c2e14d Type: SHA-1