Identification of Specific Chondroitin Sulfate Species in Cutaneous Autoimmune Disease

Abstract

SummaryCutaneous lupus erythematosus and dermatomyositis (DM) are chronic inflammatory diseases of the skin with accumulated dermal mucin. Earlier work has shown chondroitin sulfate (CS) accumulation within the dermis of discoid lupus erythematosus (DLE), subacute cutaneous lupus erythematosus (SCLE), and DM lesions compared with control skin. Immunohistochemistry for C4S revealed a greater density in DLE and DM lesions, whereas SCLE lesions did not differ from controls. Scleredema and scleromyxedema are attributed to increased hyaluronic acid, and lesional samples from these diseases also demonstrated accumulated dermal C4S. Interferon-γ and interleukin-1α, but not interferon-α, treatment of cultured dermal fibroblasts induced mRNA expression of CHST-11, which attaches sulfates to the 4-position of unsulfated chondroitin. These studies on possible CS core proteins revealed that serglycin, known to have C6S side chains in endothelial cells, had greater density within DM dermal endothelia but not in DLE or SCLE, following the pattern of C6S overexpression reported previously. CD44 variants expand the CS binding repertoire of the glycoprotein; CD44v7 co-localized to the distribution of C4S in DLE lesions, a finding not observed in DM, SCLE lesions, or controls. Because C4S and C6S have immunologic effects, their dysregulation in cutaneous mucinoses may contribute to the pathogenesis of these disorders. (J Histochem Cytochem 59:780-790, 2011)

The role of PSMB9 upregulated by interferon signature in the pathophysiology of cutaneous lesions of dermatomyositis and systemic lupus erythematosus

“…reported that both HA and CS were significantly elevated in discoid lupus erythematosus (DLE) by specific stains, while DM lesional dermis accumulated mainly CS but not HA . Kim and Werth also revealed increased accumulation of chondroitin‐4‐sulfate in DLE and DM lesions compared with control skin by immunohistochemical analyses . Our study is the first to focus on HS in these diseases, and identified the TGF‐β2–ΔDiHS‐diS1 pathway as being responsible for the specific molecular changes in DM skin.…”

“…35 Kim and Werth also revealed increased accumulation of chondroitin-4-sulfate in DLE and DM lesions compared with control skin by immunohistochemical analyses. 36 Our study is the first to focus on HS in these diseases, and identified the TGF-b2-DDiHS-diS1 pathway as being responsible for the specific molecular changes in DM skin. TGF-b2 expression was increased in the epidermis only of DM skin, and TGF-b2 induced DDiHS-diS1 in cultured dermal fibroblasts.…”

Gottron's Papules Exhibit Dermal Accumulation of CD44 Variant 7 (CD44v7) and Its Binding Partner Osteopontin: A Unique Molecular Signature

“…We have previously shown CD44v7 expression in DLE skin (Kim and Werth, 2011). However, osteopontin is not found in abundance within DLE lesions, and accordingly the osteopontin/CD44v7 complex is not seen.…”

Multiple skin‐colored papules on the face and upper extremities

“…A fibroblast dysfunction has been suggested, which may lead to increased synthesis of glycosaminoglycans [6]. Factors such as tumor necrosis factor alpha and beta (TNF-α, β) interleukins-1 and -6 (IL-1,-6), transforming growth factor beta (TGF-β) and polyclonal or monoclonal immunoglobulins may promote this process [7].…”