PMID- 35108369 OWN - NLM STAT- MEDLINE DCOM- 20221010 LR - 20221017 IS - 1462-0332 (Electronic) IS - 1462-0324 (Linking) VI - 61 IP - 10 DP - 2022 Oct 6 TI - Carbamylation of beta2-glycoprotein I generates new autoantigens for antiphospholipid syndrome: a new tool for diagnosis of 'seronegative' patients. PG - 4187-4197 LID - 10.1093/rheumatology/keac045 [doi] AB - OBJECTIVES: Antiphospholipid syndrome (APS) is a prothrombotic condition defined by recurrent thrombosis, pregnancy complications and circulating antiphospholipid antibodies (aPL), including anti-beta2-glycoprotein I (beta2-GPI). In clinical practice it is possible to find patients with APS persistently negative for the aPL tests according to Sydney criteria ('seronegative APS', SN-APS). Recently, several autoimmune responses have been described as a consequence of post-translational modifications of their target autoantigens. This study was undertaken to test carbamylated-beta2-GPI (Carb-beta2-GPI) as a new autoantigen of APS. METHODS: beta2-GPI was carbamylated by potassium cyanate and used to investigate its effect on monocyte-derived dendritic cell (moDC) phenotype and function. Sera from 114 SN-APS patients, 60 APS, 20 patients with RA, 20 non-APS thrombosis and 50 healthy donors were analysed for anti-Carb-beta2-GPI by ELISA. RESULTS: Carb-beta2-GPI is able to activate moDCs, inducing upregulation of CD80, CD86 and CD40, activation of extracellular signal-regulated kinase, p38 mitogen-activated protein kinase and nuclear factor-kappaB, and IL-12p70 release. Serological results showed that both 37/114 SN-APS (32.46%) and 23/60 APS (38.33%) patients resulted positive for anti-Carb-beta2-GPI. Interestingly, SN-APS patients who tested positive for anti-Carb-beta2-GPI showed a higher prevalence of thrombocytopenia (P = 0.04, likelihood positive ratio of 3.9). CONCLUSION: Data obtained from both functional tests on moDCs and immunological approaches prompted identification of Carb-beta2-GPI as a 'new' antigenic target in APS. In particular, anti-Carb-beta2-GPI revealed a potential usefulness in identification of a significant proportion of SN-APS patients. Moreover, since patients who tested positive for anti-Carb-beta2-GPI reported a high risk of thrombocytopenia, this test may be considered a suitable approach in the clinical evaluation of SN-APS. CI - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com. FAU - Capozzi, Antonella AU - Capozzi A AD - Department of Experimental Medicine, 'Sapienza' University of Rome. FAU - Truglia, Simona AU - Truglia S AD - Rheumatology, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University. FAU - Buttari, Brigitta AU - Buttari B AD - Department of Cardiovascular and Endocrine-Metabolic Diseases, and Aging, Istituto Superiore di Sanita, Viale Regina Elena, Rome, Italy. FAU - Recalchi, Serena AU - Recalchi S AD - Department of Experimental Medicine, 'Sapienza' University of Rome. FAU - Riitano, Gloria AU - Riitano G AD - Department of Experimental Medicine, 'Sapienza' University of Rome. FAU - Manganelli, Valeria AU - Manganelli V AD - Department of Experimental Medicine, 'Sapienza' University of Rome. FAU - Mancuso, Silvia AU - Mancuso S AD - Rheumatology, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University. FAU - Alessandri, Cristiano AU - Alessandri C AD - Rheumatology, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University. FAU - Longo, Agostina AU - Longo A AD - Department of Experimental Medicine, 'Sapienza' University of Rome. FAU - Mattei, Vincenzo AU - Mattei V AD - Department of Experimental Medicine, 'Sapienza' University of Rome. AD - Biomedicine and Advanced Technologies Rieti Center, Sabina Universitas, Rieti, Italy. FAU - Profumo, Elisabetta AU - Profumo E AD - Department of Cardiovascular and Endocrine-Metabolic Diseases, and Aging, Istituto Superiore di Sanita, Viale Regina Elena, Rome, Italy. FAU - Garofalo, Tina AU - Garofalo T AD - Department of Experimental Medicine, 'Sapienza' University of Rome. FAU - Misasi, Roberta AU - Misasi R AD - Department of Experimental Medicine, 'Sapienza' University of Rome. FAU - Conti, Fabrizio AU - Conti F AD - Rheumatology, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University. FAU - Sorice, Maurizio AU - Sorice M AD - Department of Experimental Medicine, 'Sapienza' University of Rome. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Rheumatology (Oxford) JT - Rheumatology (Oxford, England) JID - 100883501 RN - 0 (Antibodies, Antiphospholipid) RN - 0 (Autoantigens) RN - 0 (NF-kappa B) RN - 0 (beta 2-Glycoprotein I) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Antibodies, Antiphospholipid MH - *Antiphospholipid Syndrome/complications MH - Autoantigens MH - Extracellular Signal-Regulated MAP Kinases MH - Female MH - Humans MH - NF-kappa B MH - Pregnancy MH - Protein Carbamylation MH - *Thrombocytopenia/complications MH - *Thrombosis/etiology MH - beta 2-Glycoprotein I MH - p38 Mitogen-Activated Protein Kinases OTO - NOTNLM OT - antiphospholipid syndrome OT - carbamylation OT - neo-epitopes OT - seronegative APS OT - beta2-GPI-glycoprotein I EDAT- 2022/02/03 06:00 MHDA- 2022/10/12 06:00 CRDT- 2022/02/02 17:15 PHST- 2021/10/01 00:00 [received] PHST- 2021/12/31 00:00 [revised] PHST- 2022/02/03 06:00 [pubmed] PHST- 2022/10/12 06:00 [medline] PHST- 2022/02/02 17:15 [entrez] AID - 6520422 [pii] AID - 10.1093/rheumatology/keac045 [doi] PST - ppublish SO - Rheumatology (Oxford). 2022 Oct 6;61(10):4187-4197. doi: 10.1093/rheumatology/keac045.