Complement-Activating Immune Deposits in Systemic Lupus Erythematosus Skin

Abstract

Immune deposits at the cutaneous basement membrane zone are a characteristic feature of systemic lupus erythematosus. Previous studies using immunofluorescent methods to detect complement components have provided evidence that some deposits contain immune complexes capable of activating complement. However, this important biologic property of complexes has not been detected or measured using functional assays, and it has not been determined whether immune deposits can activate complement at the basement membrane zone. In this study immune deposits in biopsies of lupus skin have been examined using direct immunofluorescence for the third component of complement (C3) to detect complement deposited in vivo. In addition, the deposits have been studied using the leukocyte attachment assay and indirect C3 binding immunofluorescence to detect and measure complement activation at the basement membrane zone in vitro. The results show that complement activation occurs at the basement membrane in some but not all lupus skin containing immunoglobulin deposits, that deposits differ quantitatively in their ability to activate complement, and that direct C3 immunofluorescence is a relatively insensitive method for detecting complement-activating complexes. The results provide functional evidence suggesting that immune deposits in some lupus skin are complement-activating complexes and potentially capable of activating complement at the basement membrane in vivo. Furthermore, the results suggest functional assays for evaluating complement-activating complexes may be valuable supplements to immunofluorescence in exploring the relationship between immune deposits and systemic and cutaneous disease.

Direct Immunofluorescence in Cutaneous and Systemic Lupus Erythematosus: A Literature Review

“…There was a positive result in 42%-100% lesion cases, and 32%-92.9% in non-lesion cases. 7,16,[20][21][22][23][24][25][26][27][28] The pattern of immunodeposition at the DEJ was homogenous, thready, strippled, granular, and linear. A homogenous pattern was defined as a thick, solid, well-demarcated, continued line at the DEJ.…”

“…The common pattern and immunodeposits at the DEJ were granular and IgM, respectively. 20,23,29 DIF tests of LE-specific skin lesions (Table 1)…”

Complement‐independent blistering mechanisms in bullous pemphigoid

“…Complements are activated in many skin diseases, so complement deposition can be seen in some inflammatory skin diseases, such as lichen planus, lupus and even atopic dermatitis . In addition, a previous report showed that the C3b degradation product C3d was observed at the dermal‐epidermal junction even in normal human skin .…”