c5619b917f55190d86784d16271ca0b1 pmc_34945819.pdf a94680f2817ae9e6630c3bfb1b5ad2b6d5afc1c2 pmc_34945819.pdf a9754d956278081c73901e846bc79d39802393905a408e9fe3f53c36ad8ef09f pmc_34945819.pdf Title: Assessing Blood-Based Biomarkers to Define a Therapeutic Window for Natalizumab Subject: Natalizumab is a monoclonal antibody that binds CD49d. Although it is one of the most effective treatments for Relapsing-Remitting Multiple Sclerosis (RRMS), a dosing regimen has not been optimized for safety and efficacy in individual patients. We aimed to identify biomarkers to monitor Natalizumab treatment and to establish a personalized dose utilizing an ongoing longitudinal study in 29 RRMS patients under Natalizumab with standard interval dose (SD) of 300 mg/4 wks or extended interval dose (EID) of 300 mg/6 wks. Blood samples were analyzed by flow cytometry to determine CD49d saturation and expression in several T and B lymphocytes subpopulations. Each patient was analyzed at two different timepoints separated by 3 Natalizumab administrations. Natalizumab and sVCAM-1 levels in serum were also analyzed using ELISA. To determine the reproducibility of various markers, two different timepoints were compared and no significant differences were observed for CD49d expression nor for saturation; SD patients had higher saturation levels (~80%) than EID patients (~60%). A positive correlation exists between CD49d saturation and Natalizumab serum levels. CD49d expression and saturation are stable parameters that could be used as biomarkers in the immunomonitoring of Natalizumab treatment. Moreover, Natalizumab and sVCAM-1 serum levels could be used to optimize an individual’s dosing schedule. Keywords: multiple sclerosis; natalizumab; extended interval dose; biomarker; CD49d; sVCAM-1; immunomonitoring; personalized dose Author: Júlia Granell-Geli, Cristina Izquierdo-Gracia, Ares Sellés-Rius, Aina Teniente-Serra, Silvia Presas-Rodríguez, María José Mansilla, Luis Brieva, Javier Sotoca, María Alba Mañé-Martínez, Ester Moral, Irene Bragado, Susan Goelz, Eva Martínez-Cáceres and Cristina Ramo-Tello Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Dec 13 10:51:39 2021 CET ModDate: Mon Dec 13 10:54:44 2021 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 19 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 7869008 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- CMRYXI+VnURWPalladioL Type 1 Custom yes yes no 10 0 WGJQVI+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 BBMEWA+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 EJDTVO+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 JDWIZJ+EURM10 Type 1 Builtin yes yes no 28 0 OSMCID+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 UIJACC+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 40 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 43 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 65 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 69 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 73 0 QMDDXF+CMSY10 Type 1 Builtin yes yes no 88 0 XIGCQR+Dingbats Type 1 Builtin yes yes no 98 0 URYLRZ+URWPalladioL-BoldItal Type 1 Custom yes yes no 102 0 ZYYJXI+EURB10 Type 1 Builtin yes yes no 124 0 CRJHCU+PazoMath-Italic Type 1 Builtin yes yes no 128 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-10-21 02:39:57 CEST RepresentationInformation: pmc_34945819.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-31 12:06:36 CEST Size: 7869008 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 363 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Children: Item: Title: Study Design Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Flow Cytometry Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Children: Item: Title: Whole Blood Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: PBMCs Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Serum Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Children: Item: Title: CD49d Is a Good Biomarker to Monitor Natalizumab Treatment Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Extended Interval Dosing Reduces CD49d Saturation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: CD29 and 7-Integrin Are Not Good Biomarkers to Monitor Natalizumab Treatment Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Natalizumab and sVCAM-1 Are Putative Serum Biomarkers to Monitor the Treatment Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Natalizumab Levels in Serum Correlate with CD49d Saturation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Discussion and Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Info: Title: Assessing Blood-Based Biomarkers to Define a Therapeutic Window for Natalizumab Author: Júlia Granell-Geli, Cristina Izquierdo-Gracia, Ares Sellés-Rius, Aina Teniente-Serra, Silvia Presas-Rodríguez, María José Mansilla, Luis Brieva, Javier Sotoca, María Alba Mañé-Martínez, Ester Moral, Irene Bragado, Susan Goelz, Eva Martínez-Cáceres and Cristina Ramo-Tello Subject: Natalizumab is a monoclonal antibody that binds CD49d. Although it is one of the most effective treatments for Relapsing-Remitting Multiple Sclerosis (RRMS), a dosing regimen has not been optimized for safety and efficacy in individual patients. We aimed to identify biomarkers to monitor Natalizumab treatment and to establish a personalized dose utilizing an ongoing longitudinal study in 29 RRMS patients under Natalizumab with standard interval dose (SD) of 300 mg/4 wks or extended interval dose (EID) of 300 mg/6 wks. Blood samples were analyzed by flow cytometry to determine CD49d saturation and expression in several T and B lymphocytes subpopulations. Each patient was analyzed at two different timepoints separated by 3 Natalizumab administrations. Natalizumab and sVCAM-1 levels in serum were also analyzed using ELISA. To determine the reproducibility of various markers, two different timepoints were compared and no significant differences were observed for CD49d expression nor for saturation; SD patients had higher saturation levels (~80%) than EID patients (~60%). A positive correlation exists between CD49d saturation and Natalizumab serum levels. CD49d expression and saturation are stable parameters that could be used as biomarkers in the immunomonitoring of Natalizumab treatment. Moreover, Natalizumab and sVCAM-1 serum levels could be used to optimize an individual’s dosing schedule. Keywords: multiple sclerosis; natalizumab; extended interval dose; biomarker; CD49d; sVCAM-1; immunomonitoring; personalized dose Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Dec 13 10:51:39 CET 2021 ModDate: Mon Dec 13 10:54:44 CET 2021 ID: 0x733597d8d646b42ae3c1473b67918b4e, 0x733597d8d646b42ae3c1473b67918b4e Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: OSMCID+VnURWPalladioL-Bold FontSubset: true FirstChar: 161 LastChar: 243 FontDescriptor: FontName: OSMCID+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: CRJHCU+PazoMath-Italic FontSubset: true FirstChar: 98 LastChar: 98 FontDescriptor: FontName: CRJHCU+PazoMath-Italic Flags: Symbolic FontBBox: -70, -277, 902, 733 FontFile: true Font: BaseFont: XIGCQR+Dingbats FontSubset: true FirstChar: 226 LastChar: 226 FontDescriptor: FontName: XIGCQR+Dingbats Flags: Symbolic FontBBox: -1, -143, 981, 819 FontFile: true Font: BaseFont: BBMEWA+URWPalladioL-Bold FontSubset: true FirstChar: 2 LastChar: 241 FontDescriptor: FontName: BBMEWA+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: URYLRZ+URWPalladioL-BoldItal FontSubset: true FirstChar: 110 LastChar: 110 FontDescriptor: FontName: URYLRZ+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: EJDTVO+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: EJDTVO+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: QMDDXF+CMSY10 FontSubset: true FirstChar: 0 LastChar: 14 FontDescriptor: FontName: QMDDXF+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: CMRYXI+VnURWPalladioL FontSubset: true FirstChar: 161 LastChar: 243 FontDescriptor: FontName: CMRYXI+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: JDWIZJ+EURM10 FontSubset: true FirstChar: 11 LastChar: 22 FontDescriptor: FontName: JDWIZJ+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: ZYYJXI+EURB10 FontSubset: true FirstChar: 12 LastChar: 12 FontDescriptor: FontName: ZYYJXI+EURB10 Flags: Symbolic FontBBox: -30, -247, 1178, 723 FontFile: true Font: BaseFont: WGJQVI+URWPalladioL-Ital FontSubset: true FirstChar: 3 LastChar: 122 FontDescriptor: FontName: WGJQVI+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 35, 759, 176, 795 Annotation: Subtype: Link Rect: 515, 759, 560, 795 Annotation: Subtype: Link Rect: 130, 662, 141, 675 Annotation: Subtype: Link Rect: 355, 662, 366, 675 Annotation: Subtype: Link Rect: 260, 649, 271, 663 Annotation: Subtype: Link Rect: 504, 636, 515, 650 Annotation: Subtype: Link Rect: 54, 346, 154, 355 Annotation: Subtype: Link Rect: 35, 336, 64, 343 Annotation: Subtype: Link Rect: 35, 162, 97, 184 Annotation: Subtype: Link Rect: 153, 89, 154, 98 Annotation: Subtype: Link Rect: 35, 77, 147, 86 Annotation: Subtype: Link Rect: 486, 93, 493, 102 ActionDest: 193 Annotation: Subtype: Link Rect: 549, 80, 556, 89 ActionDest: 193 Annotation: Subtype: Link Rect: 131, 17, 269, 28 Annotation: Subtype: Link Rect: 421, 17, 558, 28 Annotation: Subtype: Link Rect: 35, 458, 87, 477 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 255, 686, 262, 695 ActionDest: 193 Annotation: Subtype: Link Rect: 263, 686, 270, 695 ActionDest: 193 Annotation: Subtype: Link Rect: 193, 674, 200, 683 ActionDest: 193 Annotation: Subtype: Link Rect: 201, 674, 208, 683 ActionDest: 193 Annotation: Subtype: Link Rect: 257, 649, 264, 658 ActionDest: 193 Annotation: Subtype: Link Rect: 264, 649, 271, 658 ActionDest: 193 Annotation: Subtype: Link Rect: 300, 611, 307, 620 ActionDest: 193 Annotation: Subtype: Link Rect: 532, 561, 544, 570 ActionDest: 193 Annotation: Subtype: Link Rect: 302, 536, 314, 545 ActionDest: 193 Annotation: Subtype: Link Rect: 384, 511, 396, 520 ActionDest: 193 Annotation: Subtype: Link Rect: 397, 511, 409, 520 ActionDest: 193 Annotation: Subtype: Link Rect: 221, 498, 232, 507 ActionDest: 193 Annotation: Subtype: Link Rect: 531, 486, 543, 495 ActionDest: 193 Annotation: Subtype: Link Rect: 544, 485, 556, 495 ActionDest: 193 Annotation: Subtype: Link Rect: 387, 448, 399, 457 ActionDest: 193 Annotation: Subtype: Link Rect: 356, 435, 368, 444 ActionDest: 193 Annotation: Subtype: Link Rect: 343, 360, 355, 369 ActionDest: 193 Annotation: Subtype: Link Rect: 532, 335, 544, 344 ActionDest: 193 Annotation: Subtype: Link Rect: 256, 297, 268, 306 ActionDest: 193 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 231, 332, 243, 342 ActionDest: 193 Annotation: Subtype: Link Rect: 373, 192, 387, 204 ActionDest: 166 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 484, 607, 499, 619 ActionDest: 166 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 191, 621, 198, 631 ActionDest: 95 Annotation: Subtype: Link Rect: 412, 251, 419, 263 ActionDest: 106 Annotation: Subtype: Link Rect: 199, 238, 206, 250 ActionDest: 106 Annotation: Subtype: Link Rect: 508, 201, 515, 213 ActionDest: 106 Annotation: Subtype: Link Rect: 483, 188, 490, 200 ActionDest: 106 Annotation: Subtype: Link Rect: 538, 113, 545, 125 ActionDest: 106 Page: Sequence: 6 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 261, 641, 268, 653 ActionDest: 115 Annotation: Subtype: Link Rect: 527, 604, 534, 616 ActionDest: 115 Annotation: Subtype: Link Rect: 543, 553, 550, 566 ActionDest: 115 Annotation: Subtype: Link Rect: 229, 478, 236, 490 ActionDest: 115 Annotation: Subtype: Link Rect: 483, 466, 497, 478 ActionDest: 175 Annotation: Subtype: Link Rect: 234, 101, 241, 114 ActionDest: 121 Annotation: Subtype: Link Rect: 356, 101, 363, 114 ActionDest: 121 Annotation: Subtype: Link Rect: 444, 89, 459, 101 ActionDest: 175 Annotation: Subtype: Link Rect: 478, 89, 493, 101 ActionDest: 184 Annotation: Subtype: Link Rect: 275, 77, 282, 88 ActionDest: 121 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 364, 133, 379, 145 ActionDest: 184 Annotation: Subtype: Link Rect: 253, 108, 260, 120 ActionDest: 135 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 229, 221, 236, 233 ActionDest: 141 Annotation: Subtype: Link Rect: 292, 159, 299, 171 ActionDest: 141 Annotation: Subtype: Link Rect: 380, 146, 387, 158 ActionDest: 141 Page: Sequence: 10 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 454, 679, 461, 691 ActionDest: 150 Annotation: Subtype: Link Rect: 434, 400, 446, 409 ActionDest: 193 Annotation: Subtype: Link Rect: 449, 400, 461, 409 ActionDest: 193 Annotation: Subtype: Link Rect: 366, 212, 378, 221 ActionDest: 193 Annotation: Subtype: Link Rect: 465, 199, 477, 208 ActionDest: 193 Annotation: Subtype: Link Rect: 477, 199, 489, 208 ActionDest: 193 Annotation: Subtype: Link Rect: 268, 74, 280, 83 ActionDest: 193 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 378, 471, 390, 480 ActionDest: 193 Annotation: Subtype: Link Rect: 238, 383, 250, 392 ActionDest: 196 Annotation: Subtype: Link Rect: 253, 383, 265, 392 ActionDest: 196 Annotation: Subtype: Link Rect: 398, 358, 410, 367 ActionDest: 193 Annotation: Subtype: Link Rect: 231, 280, 238, 292 ActionDest: 121 Annotation: Subtype: Link Rect: 296, 170, 308, 179 ActionDest: 193 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 489, 534, 500, 543 ActionDest: 196 Annotation: Subtype: Link Rect: 206, 433, 213, 443 ActionDest: 193 Annotation: Subtype: Link Rect: 214, 433, 226, 443 ActionDest: 196 Annotation: Subtype: Link Rect: 347, 421, 359, 430 ActionDest: 196 Annotation: Subtype: Link Rect: 331, 383, 343, 392 ActionDest: 196 Annotation: Subtype: Link Rect: 343, 383, 355, 392 ActionDest: 196 Annotation: Subtype: Link Rect: 434, 371, 446, 380 ActionDest: 196 Annotation: Subtype: Link Rect: 531, 371, 543, 380 ActionDest: 196 Annotation: Subtype: Link Rect: 543, 371, 555, 380 ActionDest: 196 Annotation: Subtype: Link Rect: 544, 205, 550, 217 ActionDest: 106 Annotation: Subtype: Link Rect: 340, 155, 347, 167 ActionDest: 150 Annotation: Subtype: Link Rect: 297, 145, 309, 154 ActionDest: 196 Annotation: Subtype: Link Rect: 348, 82, 360, 91 ActionDest: 196 Page: Sequence: 14 Annotations: Annotation: Subtype: Link Rect: 301, 710, 313, 719 ActionDest: 193 Annotation: Subtype: Link Rect: 314, 710, 325, 719 ActionDest: 196 Annotation: Subtype: Link Rect: 404, 659, 416, 669 ActionDest: 196 Annotation: Subtype: Link Rect: 419, 659, 431, 669 ActionDest: 196 Page: Sequence: 15 Page: Sequence: 16 Page: Sequence: 17 Page: Sequence: 18 Annotations: Annotation: Subtype: Link Rect: 520, 717, 557, 728 Annotation: Subtype: Link Rect: 59, 706, 95, 716 Annotation: Subtype: Link Rect: 136, 683, 173, 693 Annotation: Subtype: Link Rect: 179, 683, 216, 693 Annotation: Subtype: Link Rect: 95, 660, 133, 670 Annotation: Subtype: Link Rect: 59, 637, 97, 647 Annotation: Subtype: Link Rect: 300, 613, 337, 624 Annotation: Subtype: Link Rect: 519, 590, 557, 601 Annotation: Subtype: Link Rect: 59, 580, 95, 590 Annotation: Subtype: Link Rect: 306, 556, 343, 567 Annotation: Subtype: Link Rect: 95, 533, 133, 544 Annotation: Subtype: Link Rect: 139, 533, 175, 544 Annotation: Subtype: Link Rect: 59, 499, 97, 509 Annotation: Subtype: Link Rect: 103, 499, 139, 509 Annotation: Subtype: Link Rect: 59, 476, 97, 486 Annotation: Subtype: Link Rect: 103, 476, 139, 486 Annotation: Subtype: Link Rect: 131, 441, 169, 452 Annotation: Subtype: Link Rect: 498, 418, 536, 429 Annotation: Subtype: Link Rect: 210, 384, 248, 394 Annotation: Subtype: Link Rect: 254, 384, 290, 394 Annotation: Subtype: Link Rect: 286, 360, 323, 371 Annotation: Subtype: Link Rect: 171, 338, 209, 348 Annotation: Subtype: Link Rect: 95, 303, 133, 313 Annotation: Subtype: Link Rect: 139, 303, 175, 313 Annotation: Subtype: Link Rect: 95, 269, 133, 279 Annotation: Subtype: Link Rect: 425, 256, 560, 269 Annotation: Subtype: Link Rect: 56, 245, 359, 256 Annotation: Subtype: Link Rect: 59, 200, 97, 210 Annotation: Subtype: Link Rect: 103, 200, 139, 210 Annotation: Subtype: Link Rect: 178, 165, 215, 175 Annotation: Subtype: Link Rect: 400, 130, 437, 141 Annotation: Subtype: Link Rect: 244, 95, 282, 106 Annotation: Subtype: Link Rect: 417, 72, 454, 83 Page: Sequence: 19 Annotations: Annotation: Subtype: Link Rect: 401, 721, 439, 732 Annotation: Subtype: Link Rect: 226, 687, 264, 697 Annotation: Subtype: Link Rect: 261, 652, 299, 663 Annotation: Subtype: Link Rect: 195, 618, 232, 628 Annotation: Subtype: Link Rect: 472, 594, 510, 605 Annotation: Subtype: Link Rect: 162, 561, 199, 571 Annotation: Subtype: Link Rect: 205, 561, 241, 571 Annotation: Subtype: Link Rect: 442, 537, 479, 548 Annotation: Subtype: Link Rect: 485, 537, 521, 548 Annotation: Subtype: Link Rect: 140, 503, 177, 513 Annotation: Subtype: Link Rect: 184, 503, 220, 513 Annotation: Subtype: Link Rect: 202, 469, 240, 479 Annotation: Subtype: Link Rect: 246, 469, 282, 479 Annotation: Subtype: Link Rect: 59, 434, 97, 444 Annotation: Subtype: Link Rect: 103, 434, 139, 444 Annotation: Subtype: Link Rect: 513, 410, 550, 421 Annotation: Subtype: Link Rect: 302, 387, 339, 398 Annotation: Subtype: Link Rect: 345, 387, 382, 398 Annotation: Subtype: Link Rect: 336, 376, 560, 388 Annotation: Subtype: Link Rect: 56, 364, 301, 375 Checksum: af248ad5 Type: CRC32 Checksum: c5619b917f55190d86784d16271ca0b1 Type: MD5 Checksum: a94680f2817ae9e6630c3bfb1b5ad2b6d5afc1c2 Type: SHA-1