Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
HMGB1 Is An Important Mediator in Cutaneous Inflammation in Systemic Lupus Erythematosus (SLE).
Abdulahad, Deena A., Westra, Johanna, Horst, Gerda, Limburg, Pieter C., Kallenberg, Cees GM, Bijl, Marc
Systemic Lupus Erythematosus (SLE) is systemic autoimmune disease affecting many organs. Sunlight sensitivity is one of the characteristics of SLE, present in about one third to half of the patients. When exposed to physiological amounts of UVB these patients develop inflammatory skin lesions in the vicinity of apoptotic cells. High mobility group box 1 (HMGB1) is a DNA binding protein that is released from apoptotic cells and is secreted by activated cells. HMGB1 exerts its inflammatory actions through binding to several receptors such as RAGE (receptor for advanced glycation end products) and Toll-like receptors (TLRs) 2, 4, 7, and 9.
To investigate whether HMGB1 release contributes to the development of inflammatory skin lesions in SLE patients after UVB exposure.
Eleven SLE patients and 10 healthy controls (HC) were exposed to a standard dose UVB. Biopsies were taken before and 1, 3, and 10 days after irradiation. Paraffin embedded sections were stained for HMGB1, CD3 and CD68, and frozen skin biopsies were analysed for mRNA expression of IL-8, HMGB1, RAGE, and TLRs (2, 4, 7 and 9) using RT-PCR. Primary keratinocytes were cultured and irradiated with UVB light for different timepoints. HMGB1 and IL-8 release were measured in supernatants by Western Blotting and mRNA expression of above mentioned markers were determined.
A significant higher release of HMGB1 from the nucleus was seen in the un-irradiated skin of SLE patients compared to HC. Also after UVB irradiation, HMGB1 release was significantly higher in SLE patients compared to HC at all time points and HMGB1 release was correlated with presence of CD3 and CD68 positive cells. Only HMGB1 mRNA levels were increased in unirradiated skin of SLE patients compared to HC. After UVB mRNA levels of HMGB1, RAGE, TLR 2, 4, 7, and 9 all decreased and were lowest at day 3, whereas mRNA levels of IL-8 increased 24 hours after UVB irradiation without difference between patients and HC. Primary keratinocytes released HMGB1 and IL-8 into the supernatant starting from 24 hours after UVB irradiation.
HMGB1 protein release and mRNA expression are higher in the skin of SLE patients compared to HC. Upon UVB exposure release of HMGB1 in SLE further increases suggesting that SLE skin is more prone to release of HMGB1. As this release correlated with presence of macrophages and lymphocytes and as mRNA of the HMGB1 receptors before and after UV exposure are present in SLE patients our data suggest that HMGB1 release in SLE might be an important mediator of skin inflammation in SLE.
To cite this abstract, please use the following information:
Abdulahad, Deena A., Westra, Johanna, Horst, Gerda, Limburg, Pieter C., Kallenberg, Cees GM, Bijl, Marc; HMGB1 Is An Important Mediator in Cutaneous Inflammation in Systemic Lupus Erythematosus (SLE). [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1659