There induces cell proliferation and established malignancy (Duffy

are questions about the mechanisms that maintain the persistence of autoreactive
cells in autoimmune disorders (Conti-Fine et
al., 2006). Rheumatoid arthritis (RA) is an inflammatory
disease with autoimmune nature that both T and B cells have central role in its
pathogenesis through reactivity to self-antigen  (Panayi, 2005). It is suggested that certain inhibitor of
apoptosis proteins (IAPs) that are overexpressed in malignant cells might also
participate in pathologic survival of autoreactive immune cells in autoimmune
disease including RA. IAPs are a family of functionally and
structurally-related proteins that preventing the cell from undergoing cell
death, specifically in cancers (LaCasse et al.,
2008). Survivin is a multifunctional protein that
belongs to the IAPs family and is a candidate for the stability of autoreactive
immune cells (Li, 2003). This molecule participates in cell division in
nucleus, whereas mitochondrial/cytoplasmic survivin inhibits apoptosis and
induces cell proliferation and established malignancy (Duffy et al.,
2007, Nogueira-Ferreira et al., 2013). Called baculoviral
inhibitor of apoptosis repeat-containing 5 or BIRC5 is another name
of survivn because the gene of the same name (BIRC5 gene) encodes this molecule (Pu et al., 2015). The BIRC5 gene creates at least four
splice variants, including survivin-WT, survivin-2B, survivin-? Ex3 and
survivin-3B, which result from alternative splicing (Badran et al.,
2004). The proto-oncogene survivin as a therapeutic
target for cancer has attracted increasing attention since 2002. It has been
reported that some other tissues including the synovial tissue (ST) and lymphocytes of humans and animals with autoimmune
disease also expresses survivin, therefore it can be considered an appropriate
linker between cancer and autoimmunity (Kusner et al.,
2014). With respect to the increased cell
proliferation and resistance to apoptosis that leads to increased numbers of fibroblast-like
synoviocytes (FLS) and chronic inflammatory cells in rheumatoid joints (Pope, 2002), many studies have focused on survivin as anti-apopototic molecule in RA pathogenesis. In inflammatory
condition, survivin increases antigen presentation, retains the autoreactive
cells and leads to production of autoantibodies. Survivin has been shown
enriched in leukocytes in multiple sclerosis (Sharief and
Semra, 2001) myasthenia gravis (Kusner et al.,
2014) systemic sclerosis (Mokuda et al.,
2015b) pulmonary arterial hypertension (McMurtry et al.,
2005) ,rheumatoid arthritis (Bokarewa et al.,
2005), psoriasis inflammatory bowel diseases (De Souza et al.,
2012) and lichen planus (Chaiyarit et
al., 2009). Survivin can be considered a diagnostic and
prognostic marker in several disorders including rheumatoid arthritis,
psoriasis, systemic sclerosis, multiple sclerosis and inflammatory bowel
diseases (Gravina et al.,
2017). Recently, there has been renewed interest in
the role of survivin in the pathogenesis of RA (Wasén et al.,
2017, Shi et al., 2017). The observation of high level of circulating
survivin in non-malignant conditions and its correlation to the development and
progression of joint destruction prompted researcher to analyses the origin of
survivin in these patients. The role of survivin in RA has been explored in
several studies. High levels of the survivin in the plasma and synovial fluids (SF)
of RA patients compared to healthy subjects has been reported and patients with
erosive RA had a significantly higher plasma level of survivin compared to
non-erosive RA patients (Bokarewa et al.,
2005). Moreover, decrease of survivin levels during
treatment is associated with better clinical responses (Levitsky et al.,
2015). A significant difference in the survivin
expression in the peripheral blood lymphocytes between the early untreated and
normal control group has been detected as well (Chen et al.,
2013). Taken together, in the context of noncancer
pathology, such as RA, survivin has emerged as a feature related to severe
joint damage and poor treatment response as far as some reports implies that survivin
might aid in treatment decisions in RA disease. We systematically reviewed
published research to gather the data about non-malignant properties of survivin
with emphasis on its involvement in cellular and molecular pathology of RA
disease. It is first comprehensive review about survivn and attributed effect
of it in RA pathogenesis.