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Fig. 6 | Arthritis Research & Therapy

Fig. 6

From: Suppressed diversity of survivin splicing in active rheumatoid arthritis

Fig. 6

Graphic summary. Survivin-WT is by far the most prevalent variant of survivin in human leukocytes of the peripheral blood and of the bone marrow. Survivin-WT is known to be an efficient IAP, forming complexes with Smac/Diablo to prevent its release from mitochondria, and with X-linked inhibitor of apoptosis (XIAP) to inactivate caspase-3 (Casp3) and caspase-9 (Casp9). Homodimers of survivin-WT in the nucleus participate in the formation of chromosomal passenger complex supporting mitosis. Alternative splice variants survivin-2B and survivin-ΔEx3 have been suggested to form heterodimers with survivin-WT preventing its anti-apoptotic and pro-mitotic functions. Active rheumatoid arthritis (RA) is characterised by low survivin-2B/WT and survivin-ΔEx3/WT ratio indicating suppressed diversity of survivin splicing. The anti-rheumatic treatment, and particularly B-cell depletion with rituximab (RTX), increased the levels of survivin-2B and survivin-ΔEx3, potentially supporting formation of heterodimers with survivin-WT. The present study showed that this changed composition of survivin splice variants associates with a decrease in the number of CD19+ B cells, serum levels of autoantibodies (AB) and of the disease activity in patients with rheumatoid arthritis. WT wild type

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