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IVIG ameliorate inflammation in collagen induced arthritis- projection for IVIG therapy in rheumatoid arthritis
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  • Gilad Halpert,
  • Itai Katz,
  • Ora Shovman,
  • Sergay Tarasov,
  • Ksenia Ganina,
  • Natalyia Petrova,
  • Milena Tocut,
  • Alexsander Volkov,
  • Iris Barshack,
  • Miri Blank,
  • Howard Amital
Gilad Halpert
Sheba Medical Center
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Itai Katz
Sheba Medical Center
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Ora Shovman
Sheba Medical Center
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Sergay Tarasov
Materia Medica Holding
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Ksenia Ganina
Materia Medica Holding
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Natalyia Petrova
Materia Medica Holding
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Milena Tocut
Edith Wolfson Medical Center
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Alexsander Volkov
Sheba Medical Center
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Iris Barshack
Sheba Medical Center
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Miri Blank
Sheba Medical Center
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Howard Amital
Sheba Medical Center
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Abstract

Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease that leads to joint destruction and disability. Despite a significant progress in administration of biological agents for RA patients, there is still a need for improved therapy. Intravenous-immunoglobulins (IVIG) , a pooled polyspecific immunoglobulin-G (IgG) extracted from 20,000 healthy subjects, showed beneficial therapeutic effect in patients with immune-deficiency, sepsis, and autoimmune diseases. The current study aim to investigate the beneficial effect of treatment with IVIG in established collagen induced arthritis in DBA/1j mice. Murine arthritis was induced in DBA/1j mice. The treatment with IVIG started when the disease was established. The clinical score was followed twice a week until day 48. The mice were bled for plasma, the paws were H&E stained. Cytokine profile in the plasma was analyzed by Luminex technology, titers of circulating anti-collagen antibodies in the plasma was tested by ELISA. Our results show that treatment with IVIG in murine, significantly rreduced the clinical arthritis score (P<0.001). Moreover, mode of action show that IVIG significantly reduced circulating level of inflammatory cytokines (IFN, IL-1β, IL-17, IL-6, TNFα) (P<0.001), inhibit anti-collagen antibodies (P < 0.001) in the plasma of CIA mice. Importantly, histopathological examination revealed that IVIG treatment prevented the migration of inflammatory immune cells into the cartilage and synovium, reduced the extent of joint damage and preserved joint architecture. Our results proved for the first time the valuable anti-inflammatory treatment of IVIG in experimental RA. We propose IVIG therapy for a subgroup of patients with as rheumatological-related diseases.

Peer review status:ACCEPTED

19 Aug 2020Submitted to Clinical & Experimental Immunology
20 Aug 2020Submission Checks Completed
20 Aug 2020Assigned to Editor
20 Aug 2020Reviewer(s) Assigned
07 Sep 2020Review(s) Completed, Editorial Evaluation Pending
08 Sep 2020Editorial Decision: Revise Minor
22 Sep 20201st Revision Received
22 Sep 2020Review(s) Completed, Editorial Evaluation Pending
22 Sep 2020Editorial Decision: Accept