PMID- 30923525 OWN - NLM STAT- MEDLINE DCOM- 20200902 LR - 20200902 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 10 DP - 2019 TI - Alarmin HMGB1 and Soluble RAGE as New Tools to Evaluate the Risk Stratification in Patients With the Antiphospholipid Syndrome. PG - 460 LID - 10.3389/fimmu.2019.00460 [doi] LID - 460 AB - Antiphospholipid antibody syndrome (APS) is a systemic autoimmune disease characterized by arterial and/or venous thrombosis, pregnancy morbidity in the presence of circulating "anti-phospholipid antibodies" (aPL). One of the main target antigens of aPL is beta(2)-glycoprotein I (beta(2)-GPI). APS may occur as a primary syndrome or associated with Systemic Lupus Erythematosus (SLE). High Mobility Group Box 1 (HMGB1) is a nuclear non-histone protein which is secreted from different type of cells during activation and/or cell death and may act as a proinflammatory mediator through ligation to its receptors, including RAGE. There is accumulating evidence that HMGB1 contributes to the pathogenesis of inflammatory and autoimmune diseases, especially SLE. In a previous study we demonstrated increased serum levels of HMGB1 in both primary and secondary APS patients. In this work we analyzed: (i) in vitro whether anti-beta(2)-GPI antibodies from APS patients may induce both a HMGB1 cellular relocation by activation of its putative receptor RAGE in platelets and monocytes and, (ii) ex vivo, serum levels of HMGB1/soluble RAGE (sRAGE) in APS patients and their possible correlation with clinical manifestations. Platelets and monocytes from healthy donors were incubated with affinity purified anti-beta(2)-GPI antibodies. HMGB1 and RAGE expression were analyzed by Western Blot. Sera from 60 consecutive APS patients (primary or secondary), diagnosed according to the Sydney Classification Criteria, were enrolled. As a control, 30 matched healthy subjects were studied. Serum levels of HMGB1 and sRAGE were analyzed by Western Blot. In vitro results showed that anti-beta(2)-GPI antibodies were able to induce RAGE activation and HMGB1 cellular relocation in both monocytes and platelets. HMGB1 and sRAGE serum levels were significantly increased in APS patients in comparison with healthy subjects (p<0.0001). Interestingly, APS patients with spontaneous recurrent abortion showed significantly higher levels of sRAGE; moreover, in APS patients a direct correlation between serum levels of HMGB1 and disease duration was detected. Our observations suggest that anti-beta(2)-GPI antibodies may trigger RAGE activation and HMGB1 cellular relocation during APS. Monitoring these molecules serum levels may represent an useful tool to evaluate the pathogenesis and risk stratification of clinical manifestations in APS. FAU - Manganelli, Valeria AU - Manganelli V AD - Dipartimento di Medicina Sperimentale, Sapienza Universita di Roma, Rome, Italy. FAU - Truglia, Simona AU - Truglia S AD - Reumatologia, Dipartimento di Medicina Interna e Specialita Mediche, Sapienza Universita di Roma, Rome, Italy. FAU - Capozzi, Antonella AU - Capozzi A AD - Dipartimento di Medicina Sperimentale, Sapienza Universita di Roma, Rome, Italy. FAU - Alessandri, Cristiano AU - Alessandri C AD - Reumatologia, Dipartimento di Medicina Interna e Specialita Mediche, Sapienza Universita di Roma, Rome, Italy. FAU - Riitano, Gloria AU - Riitano G AD - Dipartimento di Medicina Sperimentale, Sapienza Universita di Roma, Rome, Italy. FAU - Spinelli, Francesca Romana AU - Spinelli FR AD - Reumatologia, Dipartimento di Medicina Interna e Specialita Mediche, Sapienza Universita di Roma, Rome, Italy. FAU - Ceccarelli, Fulvia AU - Ceccarelli F AD - Reumatologia, Dipartimento di Medicina Interna e Specialita Mediche, Sapienza Universita di Roma, Rome, Italy. FAU - Mancuso, Silvia AU - Mancuso S AD - Reumatologia, Dipartimento di Medicina Interna e Specialita Mediche, Sapienza Universita di Roma, Rome, Italy. FAU - Garofalo, Tina AU - Garofalo T AD - Dipartimento di Medicina Sperimentale, Sapienza Universita di Roma, Rome, Italy. FAU - Longo, Agostina AU - Longo A AD - Dipartimento di Medicina Sperimentale, Sapienza Universita di Roma, Rome, Italy. FAU - Valesini, Guido AU - Valesini G AD - Reumatologia, Dipartimento di Medicina Interna e Specialita Mediche, Sapienza Universita di Roma, Rome, Italy. FAU - Sorice, Maurizio AU - Sorice M AD - Dipartimento di Medicina Sperimentale, Sapienza Universita di Roma, Rome, Italy. FAU - Conti, Fabrizio AU - Conti F AD - Reumatologia, Dipartimento di Medicina Interna e Specialita Mediche, Sapienza Universita di Roma, Rome, Italy. FAU - Misasi, Roberta AU - Misasi R AD - Dipartimento di Medicina Sperimentale, Sapienza Universita di Roma, Rome, Italy. LA - eng PT - Evaluation Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190314 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (AGER protein, human) RN - 0 (Antibodies, Antiphospholipid) RN - 0 (HMGB1 Protein) RN - 0 (HMGB1 protein, human) RN - 0 (Receptor for Advanced Glycation End Products) RN - 0 (beta 2-Glycoprotein I) SB - IM MH - Adult MH - Antibodies, Antiphospholipid/blood/immunology MH - Antiphospholipid Syndrome/blood/*immunology MH - Blood Platelets/immunology/metabolism MH - Female MH - HMGB1 Protein/blood/*immunology MH - Humans MH - Male MH - Middle Aged MH - Monocytes/immunology/metabolism MH - Receptor for Advanced Glycation End Products/blood/*immunology MH - Risk Assessment MH - beta 2-Glycoprotein I/blood/immunology PMC - PMC6426766 OTO - NOTNLM OT - HMGB1 OT - antiphospholipid syndrome OT - recurrent abortion OT - sRAGE OT - thrombosis EDAT- 2019/03/30 06:00 MHDA- 2020/09/04 06:00 PMCR- 2019/01/01 CRDT- 2019/03/30 06:00 PHST- 2018/09/28 00:00 [received] PHST- 2019/02/20 00:00 [accepted] PHST- 2019/03/30 06:00 [entrez] PHST- 2019/03/30 06:00 [pubmed] PHST- 2020/09/04 06:00 [medline] PHST- 2019/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2019.00460 [doi] PST - epublish SO - Front Immunol. 2019 Mar 14;10:460. doi: 10.3389/fimmu.2019.00460. eCollection 2019.