ba51ae87c69d35205713200a1bbe7d48 biomedicines-12-02800_1_.pdf ff5c9d9072b55758f8fa4fb9464175129214b781 biomedicines-12-02800_1_.pdf 6be7d6fa83c79e3ab44650011b843836bd93cedf58d26adf4b2b1f1f657a1dc4 biomedicines-12-02800_1_.pdf Title: Increased Risk of Myositis-Specific and Myositis-Associated Autoantibodies After COVID-19 Pandemic and Vaccination: A Spanish Multicenter Collaborative Study Subject: Background: Emerging evidence suggests that SARS-CoV-2 infection and vaccines may trigger autoimmune responses in predisposed individuals. Idiopathic inflammatory myopathies (IIMs) are diseases with diverse clinical manifestations, often associated with myositis autoantibodies (MAs). Diagnosing IIM is challenging due to limitations in classification criteria and diagnostic assays. This study aimed to describe the incidence of IIM following SARS-CoV-2 infection or vaccination and compare rates between exposures. Methods: A multicenter observational study was conducted with 788 patients from 11 Spanish referral centers. A total of 1209 autoantibodies including myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs), were analyzed using line blot immunoassay (LIA). Results: The study identified distinct patterns in aminoacyl-tRNA synthetase (ARS) antibody frequencies compared to pre-pandemic periods. Anti-PL-7 was the most prevalent ARS antibody (14.85%), while anti-Jo-1 was less frequent (7.23%). Anti-MDA5, commonly linked to SARS-CoV-2 infection, was detected in 11.68%. ANA positivity was observed in 60.66%, suggesting an autoimmune background. The most frequent diagnoses were anti-synthetase syndrome (ASSD) or IIM-non-ASSD (21.31%), followed by other systemic autoimmune diseases (SAIDs) (13.57%). Among the cohort, 91.13% received at least one dose of a messenger RNA (mRNA) COVID-19 vaccine, with a median of three doses per patient. Patients with prior SARS-CoV-2 infection or heterologous vaccination showed a higher frequency of multiple autoantibody positivity (p < 0.05), reflecting distinct immune signatures. Conclusions: This study provides valuable insights into the autoimmune risks and phenotypes associated with SARS-CoV-2 infection and vaccination, establishing a basis for further research on IIM and its link to MSAs and MAAs. Keywords: myositis autoantibodies; idiopathic inflammatory myopathies; anti-synthetase syndrome; anti-aminoacyl-tRNA synthetase autoantibodies; line blot immunoassays; coronavirus disease 2019; SARS-CoV-2 infection; COVID-19 vaccine; mRNA vaccine Author: Laura García-Bravo, Alvaro Prada, María Gutiérrez Larrañaga, Eduardo Espinosa Ros, Delia Almeida González, Dolores Martín Martínez, Telesforo Rodríguez Sánchez, Carlos Gustavo Mingorance Gámez, Aurora Jurado Roger, Rocío Aguado Álvarez, María De Las Mercedes Díaz Luna, Carmen Rodríguez Hernández, Raquel de la Varga-Martínez, María López-Cueto, Maria Rosa Julià Benique, Miriam San José-Cascón, Bibiana Quirant-Sánchez, Alba Martínez-Chamorro, Goitzane Marcaida-Benito, Pilar Teresa Timoneda Timoneda, Marta Fandos Sánchez, Beatriz Sacristán Enciso, Kauzar Mohamed Mohamed, Teresa Guerra-Galán, Ángela Villegas, Andrés Roncancio-Clavijo, Margarita Rodríguez-Mahou, Silvia Sánchez-Ramón, Miguel Fernández-Arquero, Gloria Candelas-Rodríguez, Juliana Ochoa-Grullón and on behalf of the GEAI-SEI Group Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Tue Dec 10 11:12:00 2024 CET ModDate: Tue Dec 10 11:40:13 2024 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 17 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2615727 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- YRKSID+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 IXIXPV+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 CMYWAA+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 ZDAITZ+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 XAWNGI+VnURWPalladioL Type 1 Custom yes yes yes 32 0 GOCQIR+EURM10 Type 1 Builtin yes yes yes 62 0 TNBSFT+CMSY10 Type 1 Builtin yes yes yes 73 0 MIFJGB+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 88 0 MIFJGC+PalatinoLinotype CID TrueType Identity-H yes yes yes 91 0 MIFJGD+PalatinoLinotype TrueType WinAnsi yes yes no 97 0 MIFJGF+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 100 0 MIFKBD+PalatinoLinotype TrueType MacRoman yes yes no 103 0 MIFJGB+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 159 0 MIFJGC+PalatinoLinotype CID TrueType Identity-H yes yes yes 162 0 MIFJGD+PalatinoLinotype TrueType WinAnsi yes yes no 168 0 MIFJGF+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 171 0 MIFKBD+PalatinoLinotype TrueType MacRoman yes yes no 174 0 GIZSCG+EURM7 Type 1 Builtin yes yes yes 326 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-06-26 02:08:05 CEST RepresentationInformation: biomedicines-12-02800_1_.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-06-25 19:32:08 CEST Size: 2615727 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 497 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Methods Destination: section.2 Children: Item: Title: Patients and Study Design Destination: subsection.2.1 Item: Title: Laboratory Assessment Destination: subsection.2.2 Children: Item: Title: Line Blot Immunoassay Analysis Destination: subsubsection.2.2.1 Item: Title: Indirect Immunofluorescence Assay Destination: subsubsection.2.2.2 Item: Title: Extractable Nuclear Antigen Antibodies Destination: subsubsection.2.2.3 Item: Title: Muscle and Liver Enzymes Destination: subsubsection.2.2.4 Item: Title: Analysis of HLA Typing Destination: subsubsection.2.2.5 Item: Title: Statistical Analysis Destination: subsection.2.3 Item: Title: Results Destination: section.3 Children: Item: Title: Overall Overview and Incidence of Myositis Autoantibodies Destination: subsection.3.1 Item: Title: Autoantibody Profile: Frequency and Levels Destination: subsection.3.2 Item: Title: MAs Associated with ANA Antibodies Destination: subsection.3.3 Item: Title: Antibody Association with COVID-19 Infection or Vaccination Destination: subsection.3.4 Item: Title: Description of Clinical Manifestations. Diagnosis, Treatment, and Outcomes Destination: subsection.3.5 Item: Title: HLA Typing in a Subgroup of Patients Destination: subsection.3.6 Item: Title: Discussion and Future Research Destination: section.4 Item: Title: References Destination: section.5 Info: Title: Increased Risk of Myositis-Specific and Myositis-Associated Autoantibodies After COVID-19 Pandemic and Vaccination: A Spanish Multicenter Collaborative Study Author: Laura García-Bravo, Alvaro Prada, María Gutiérrez Larrañaga, Eduardo Espinosa Ros, Delia Almeida González, Dolores Martín Martínez, Telesforo Rodríguez Sánchez, Carlos Gustavo Mingorance Gámez, Aurora Jurado Roger, Rocío Aguado Álvarez, María De Las Mercedes Díaz Luna, Carmen Rodríguez Hernández, Raquel de la Varga-Martínez, María López-Cueto, Maria Rosa Julià Benique, Miriam San José-Cascón, Bibiana Quirant-Sánchez, Alba Martínez-Chamorro, Goitzane Marcaida-Benito, Pilar Teresa Timoneda Timoneda, Marta Fandos Sánchez, Beatriz Sacristán Enciso, Kauzar Mohamed Mohamed, Teresa Guerra-Galán, Ángela Villegas, Andrés Roncancio-Clavijo, Margarita Rodríguez-Mahou, Silvia Sánchez-Ramón, Miguel Fernández-Arquero, Gloria Candelas-Rodríguez, Juliana Ochoa-Grullón and on behalf of the GEAI-SEI Group Subject: Background: Emerging evidence suggests that SARS-CoV-2 infection and vaccines may trigger autoimmune responses in predisposed individuals. Idiopathic inflammatory myopathies (IIMs) are diseases with diverse clinical manifestations, often associated with myositis autoantibodies (MAs). Diagnosing IIM is challenging due to limitations in classification criteria and diagnostic assays. This study aimed to describe the incidence of IIM following SARS-CoV-2 infection or vaccination and compare rates between exposures. Methods: A multicenter observational study was conducted with 788 patients from 11 Spanish referral centers. A total of 1209 autoantibodies including myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs), were analyzed using line blot immunoassay (LIA). Results: The study identified distinct patterns in aminoacyl-tRNA synthetase (ARS) antibody frequencies compared to pre-pandemic periods. Anti-PL-7 was the most prevalent ARS antibody (14.85%), while anti-Jo-1 was less frequent (7.23%). Anti-MDA5, commonly linked to SARS-CoV-2 infection, was detected in 11.68%. ANA positivity was observed in 60.66%, suggesting an autoimmune background. The most frequent diagnoses were anti-synthetase syndrome (ASSD) or IIM-non-ASSD (21.31%), followed by other systemic autoimmune diseases (SAIDs) (13.57%). Among the cohort, 91.13% received at least one dose of a messenger RNA (mRNA) COVID-19 vaccine, with a median of three doses per patient. Patients with prior SARS-CoV-2 infection or heterologous vaccination showed a higher frequency of multiple autoantibody positivity (p < 0.05), reflecting distinct immune signatures. Conclusions: This study provides valuable insights into the autoimmune risks and phenotypes associated with SARS-CoV-2 infection and vaccination, establishing a basis for further research on IIM and its link to MSAs and MAAs. Keywords: myositis autoantibodies; idiopathic inflammatory myopathies; anti-synthetase syndrome; anti-aminoacyl-tRNA synthetase autoantibodies; line blot immunoassays; coronavirus disease 2019; SARS-CoV-2 infection; COVID-19 vaccine; mRNA vaccine Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Tue Dec 10 11:12:00 CET 2024 ModDate: Tue Dec 10 11:40:13 CET 2024 ID: 0x3426e54e9750afcd1f768661df38476c, 0x3426e54e9750afcd1f768661df38476c Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: XAWNGI+VnURWPalladioL FontSubset: true FirstChar: 129 LastChar: 226 FontDescriptor: FontName: XAWNGI+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: IXIXPV+URWPalladioL-Bold FontSubset: true FirstChar: 2 LastChar: 241 FontDescriptor: FontName: IXIXPV+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: CMYWAA+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: CMYWAA+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: GIZSCG+EURM7 FontSubset: true FirstChar: 11 LastChar: 12 FontDescriptor: FontName: GIZSCG+EURM7 Flags: Symbolic FontBBox: -5, -243, 1229, 720 FontFile: true ToUnicode: true Font: BaseFont: TNBSFT+CMSY10 FontSubset: true FirstChar: 6 LastChar: 21 FontDescriptor: FontName: TNBSFT+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true ToUnicode: true Font: BaseFont: YRKSID+VnURWPalladioL-Bold FontSubset: true FirstChar: 129 LastChar: 226 FontDescriptor: FontName: YRKSID+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: ZDAITZ+URWPalladioL-Ital FontSubset: true FirstChar: 2 LastChar: 121 FontDescriptor: FontName: ZDAITZ+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: GOCQIR+EURM10 FontSubset: true FirstChar: 11 LastChar: 13 FontDescriptor: FontName: GOCQIR+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true ToUnicode: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 121, 279, 152, 288 Annotation: Subtype: Link Rect: 34, 267, 151, 276 Annotation: Subtype: Link Rect: 34, 164, 96, 186 Annotation: Subtype: Link Rect: 126, 90, 154, 99 Annotation: Subtype: Link Rect: 34, 78, 149, 87 Annotation: Subtype: Link Rect: 34, 756, 171, 792 Annotation: Subtype: Link Rect: 515, 756, 560, 792 Annotation: Subtype: Link Rect: 447, 642, 458, 655 Annotation: Subtype: Link Rect: 309, 616, 320, 630 Annotation: Subtype: Link Rect: 433, 616, 444, 630 Annotation: Subtype: Link Rect: 507, 591, 518, 605 Annotation: Subtype: Link Rect: 414, 567, 425, 580 Annotation: Subtype: Link Rect: 502, 554, 513, 568 Annotation: Subtype: Link Rect: 429, 541, 440, 555 Annotation: Subtype: Link Rect: 130, 17, 302, 28 Annotation: Subtype: Link Rect: 389, 17, 560, 28 Annotation: Subtype: Link Rect: 34, 424, 87, 443 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 206, 590, 213, 599 ActionDest: 347 Annotation: Subtype: Link Rect: 214, 590, 221, 599 ActionDest: 347 Annotation: Subtype: Link Rect: 341, 565, 348, 574 ActionDest: 347 Annotation: Subtype: Link Rect: 319, 515, 326, 524 ActionDest: 347 Annotation: Subtype: Link Rect: 368, 465, 375, 474 ActionDest: 347 Annotation: Subtype: Link Rect: 400, 427, 407, 436 ActionDest: 347 Annotation: Subtype: Link Rect: 475, 389, 482, 398 ActionDest: 347 Annotation: Subtype: Link Rect: 482, 389, 489, 398 ActionDest: 347 Annotation: Subtype: Link Rect: 237, 326, 244, 336 ActionDest: 347 Annotation: Subtype: Link Rect: 352, 301, 364, 310 ActionDest: 347 Annotation: Subtype: Link Rect: 326, 276, 338, 285 ActionDest: 347 Annotation: Subtype: Link Rect: 292, 201, 304, 210 ActionDest: 347 Annotation: Subtype: Link Rect: 544, 176, 556, 185 ActionDest: 347 Annotation: Subtype: Link Rect: 407, 151, 419, 160 ActionDest: 347 Annotation: Subtype: Link Rect: 269, 126, 281, 135 ActionDest: 347 Annotation: Subtype: Link Rect: 343, 88, 355, 97 ActionDest: 347 Page: Sequence: 3 Page: Sequence: 4 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 343, 284, 350, 296 ActionDest: 78 Annotation: Subtype: Link Rect: 416, 259, 423, 271 ActionDest: 78 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 212, 741, 219, 753 ActionDest: 110 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 218, 215, 225, 227 ActionDest: 113 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 209, 235, 220, 243 ActionDest: 347 Annotation: Subtype: Link Rect: 290, 107, 297, 119 ActionDest: 113 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 269, 665, 276, 677 ActionDest: 110 Annotation: Subtype: Link Rect: 435, 263, 443, 275 ActionDest: 110 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 528, 678, 535, 690 ActionDest: 110 Annotation: Subtype: Link Rect: 212, 439, 219, 451 ActionDest: 323 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 530, 590, 537, 602 ActionDest: 323 Annotation: Subtype: Link Rect: 551, 452, 558, 464 ActionDest: 323 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 351, 617, 363, 627 ActionDest: 347 Annotation: Subtype: Link Rect: 481, 592, 493, 602 ActionDest: 347 Annotation: Subtype: Link Rect: 456, 555, 468, 564 ActionDest: 347 Annotation: Subtype: Link Rect: 271, 530, 283, 539 ActionDest: 347 Annotation: Subtype: Link Rect: 310, 492, 322, 501 ActionDest: 347 Annotation: Subtype: Link Rect: 257, 241, 269, 250 ActionDest: 350 Annotation: Subtype: Link Rect: 269, 241, 281, 250 ActionDest: 350 Annotation: Subtype: Link Rect: 229, 103, 241, 112 ActionDest: 350 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 528, 706, 540, 715 ActionDest: 350 Annotation: Subtype: Link Rect: 490, 618, 502, 627 ActionDest: 350 Annotation: Subtype: Link Rect: 430, 530, 442, 539 ActionDest: 350 Annotation: Subtype: Link Rect: 219, 505, 231, 514 ActionDest: 350 Annotation: Subtype: Link Rect: 183, 430, 195, 439 ActionDest: 350 Annotation: Subtype: Link Rect: 379, 354, 391, 363 ActionDest: 350 Annotation: Subtype: Link Rect: 324, 329, 336, 338 ActionDest: 347 Annotation: Subtype: Link Rect: 544, 191, 556, 200 ActionDest: 350 Annotation: Subtype: Link Rect: 254, 153, 266, 162 ActionDest: 350 Annotation: Subtype: Link Rect: 452, 91, 464, 100 ActionDest: 347 Page: Sequence: 14 Annotations: Annotation: Subtype: Link Rect: 448, 668, 460, 677 ActionDest: 350 Annotation: Subtype: Link Rect: 265, 618, 277, 627 ActionDest: 347 Annotation: Subtype: Link Rect: 352, 568, 364, 577 ActionDest: 350 Annotation: Subtype: Link Rect: 459, 542, 471, 552 ActionDest: 350 Annotation: Subtype: Link Rect: 197, 241, 209, 250 ActionDest: 350 Page: Sequence: 15 Page: Sequence: 16 Annotations: Annotation: Subtype: Link Rect: 134, 624, 172, 634 Annotation: Subtype: Link Rect: 178, 624, 214, 634 Annotation: Subtype: Link Rect: 334, 600, 372, 611 Annotation: Subtype: Link Rect: 378, 600, 414, 611 Annotation: Subtype: Link Rect: 95, 578, 133, 588 Annotation: Subtype: Link Rect: 139, 578, 175, 588 Annotation: Subtype: Link Rect: 208, 554, 246, 565 Annotation: Subtype: Link Rect: 252, 554, 288, 565 Annotation: Subtype: Link Rect: 131, 532, 168, 542 Annotation: Subtype: Link Rect: 148, 508, 185, 519 Annotation: Subtype: Link Rect: 90, 474, 128, 484 Annotation: Subtype: Link Rect: 59, 439, 96, 450 Annotation: Subtype: Link Rect: 282, 416, 319, 427 Annotation: Subtype: Link Rect: 464, 393, 502, 404 Annotation: Subtype: Link Rect: 148, 358, 186, 369 Annotation: Subtype: Link Rect: 192, 358, 228, 369 Annotation: Subtype: Link Rect: 479, 335, 515, 346 Annotation: Subtype: Link Rect: 521, 335, 557, 346 Annotation: Subtype: Link Rect: 426, 312, 463, 323 Annotation: Subtype: Link Rect: 469, 312, 505, 323 Annotation: Subtype: Link Rect: 443, 290, 480, 300 Annotation: Subtype: Link Rect: 95, 255, 133, 265 Annotation: Subtype: Link Rect: 480, 220, 518, 231 Annotation: Subtype: Link Rect: 244, 185, 281, 196 Annotation: Subtype: Link Rect: 131, 163, 168, 173 Annotation: Subtype: Link Rect: 59, 129, 96, 139 Annotation: Subtype: Link Rect: 238, 105, 275, 116 Annotation: Subtype: Link Rect: 449, 70, 486, 81 Annotation: Subtype: Link Rect: 493, 70, 529, 81 Page: Sequence: 17 Annotations: Annotation: Subtype: Link Rect: 519, 718, 557, 729 Annotation: Subtype: Link Rect: 59, 707, 95, 718 Annotation: Subtype: Link Rect: 442, 683, 479, 694 Annotation: Subtype: Link Rect: 485, 683, 521, 694 Annotation: Subtype: Link Rect: 86, 661, 124, 671 Annotation: Subtype: Link Rect: 130, 661, 166, 671 Annotation: Subtype: Link Rect: 283, 626, 320, 637 Annotation: Subtype: Link Rect: 368, 591, 406, 602 Annotation: Subtype: Link Rect: 96, 558, 134, 568 Annotation: Subtype: Link Rect: 258, 534, 296, 545 Annotation: Subtype: Link Rect: 275, 511, 313, 522 Annotation: Subtype: Link Rect: 362, 476, 400, 487 Annotation: Subtype: Link Rect: 519, 465, 557, 476 Annotation: Subtype: Link Rect: 59, 454, 95, 464 Annotation: Subtype: Link Rect: 163, 431, 200, 441 Annotation: Subtype: Link Rect: 206, 431, 242, 441 Annotation: Subtype: Link Rect: 249, 431, 316, 441 Annotation: Subtype: Link Rect: 430, 407, 467, 418 Annotation: Subtype: Link Rect: 473, 407, 509, 418 Annotation: Subtype: Link Rect: 113, 385, 151, 395 Annotation: Subtype: Link Rect: 157, 385, 193, 395 Annotation: Subtype: Link Rect: 258, 350, 295, 361 Annotation: Subtype: Link Rect: 131, 316, 168, 326 Checksum: bcf3fd67 Type: CRC32 Checksum: ba51ae87c69d35205713200a1bbe7d48 Type: MD5 Checksum: ff5c9d9072b55758f8fa4fb9464175129214b781 Type: SHA-1 Checksum: 6be7d6fa83c79e3ab44650011b843836bd93cedf58d26adf4b2b1f1f657a1dc4 Type: SHA-256