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Clin Rheumatol. 2019 Mar;38(3):955-960. doi: 10.1007/s10067-018-4360-3. Epub 2018 Nov 10.

CIGB-814, an altered peptide ligand derived from human heat-shock protein 60, decreases anti-cyclic citrullinated peptides antibodies in patients with rheumatoid arthritis.

Author information

1
Center for Genetic Engineering and Biotechnology (CIGB), P.O. Box 6162, Havana, Cuba.
2
National Reference Center for Rheumatic Disease, 10 de Octubre Hospital, Havana, Cuba.
3
Center for Genetic Engineering and Biotechnology (CIGB), P.O. Box 6162, Havana, Cuba. mcarmen.dominguez@cigb.edu.cu.

Abstract

Rheumatoid arthritis (RA) is a chronic T cell-mediated autoimmune disease. Serum autoantibodies against cyclic citrullinated peptides (anti-CCP) are significant markers for diagnosis and prognosis of this disease. Induction of immune tolerance as therapeutic approach for RA constitutes a current research focal point. In this sense, we carried out a phase I clinical trial in RA patients with a new therapeutic candidate (called CIGB-814); which induced mechanisms associated with restoration of peripheral tolerance in preclinical studies. CIGB 814 is an altered peptide ligand (APL), derived from a CD4+ T cell epitope of human heat-shock protein 60 (HSP60), an autoantigen involved in the pathogenesis of RA. Twenty patients with moderate disease activity were included in this open label trial. Sequential dose-escalation of 1, 2.5 and 5 mg of CIGB-814 was studied. Consecutive groups of six, five, and nine patients received a subcutaneous dose weekly of the peptide during the first month and one dose monthly during the next 5 months. The peptide was well tolerated and reduced disease activity. Here, we reported the quantification of anti-CCP antibodies during the treatment with this APL and in the follow-up stage. Anti-CCP antibodies were quantified in the plasma from patients by a commercial enzyme immunoassay at baseline (T0) and at weeks 28 and 48. Results showed that CIGB-814 induced a significant reduction of anti-CCP antibodies. In addition, this decrease correlated with clinical improvement in patients assessed by Disease Activity Score in 28 joints (DAS28) criteria. These findings reinforce the therapeutic potential of CIGB-814.

KEYWORDS:

APL; Anti-CCP; CIGB-814; HSP60; Rheumatoid arthritis

PMID:
30415439
DOI:
10.1007/s10067-018-4360-3

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