• Treatments
• Basic Science

The following abstracts were written by Michelle Petri, M.D., M.P.H

Abstract LB06 Steroid Therapy Extinguishes the Interferon Alpha Signature in SLE Leukocytes
Virginia Pascual, Lynda Bennett, Edsel Arce, Victoria Cantrell, Karolina Palucka, Jacques Banchereau

The genetic predisposition to SLE can be considered in two ways - the genes that predispose to SLE itself and those genes which are "turned on" when SLE is active. Timothy Behrens and others have identified a large number of interferon-inducible genes that are turned on in SLE. At this ACR meeting, two groups have confirmed these findings. In the abstract by Pascual and colleagues, the authors reported that IV "pulse" solumedrol therapy shuts down the interferon-induced gene signature of SLE.

Editorial Comments: Thus, the search for "biomarkers" that predict active SLE and predict response to therapy may be one step further along.

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The following abstracts were written by Antony Rosen, M.D.

Abstract 234 Autoimmune responses in lupus patients to PCNA multiprotein complexes involved in cell proliferation are strongly associated with theiur structure and biological function.
Y Takasaki, T Kogure, K Kaneda, et. al.

In these very interesting studies, Takasaki and colleagues have continued their decade-long work on the autoantibody response to the proliferating cell nuclear antigen (PCNA) complex. PCNA is a large molecular complex comprising numerous components, which is the target of autoantibodies in a small proportion of patients with lupus. Previously, serum from PCNA-positive patients was shown to recognize the 34kDa PCNA subunit.

Results: In these studies, a striking number (14/40; 35%) of lupus sera which tested negative for PCNA by ELISA recognized other components of the PCNA complex by immunoblotting, implying that the PCNA complex may be a much more frequent target of the autoantibody response in SLE than previously appreciated.

Editorial Comments: The data focus additional attention on defining the circumstances in vivo in which the PCNA complex becomes visible to the immune system during initiation and propagation of lupus and similar diseases.

Abstract 241 VH4-34 anti-I/I autoantibodies recognize apoptotic cells.
A Pugh-Bernard, K Hocknell, A Cappione, J Anolik, and I Sanz

Over the past several years, there has been significant interest in defining the role of apoptotic cells as potential sources of immunogens in systemic autoimmune diseases. Several studies have demonstrated that abnormal clearance of apoptotic cells may be an important susceptibility factor in the development of lupus-like autoimmunity. Understanding the relevant pathways for clearance of apoptotic cells is a major priority.

Results: Sanz et al have been studying a subset of human autoreactive B cells (VH4-34 cells) which make antibodies specific for the blood group I/i antigen. In these studies, the investigators show that VH4-34 monoclonals or antibodies from lupus patients bind to the surface of apoptotic cells; they do not appear to recognize phosphatidylserine at this site. Although the authors do not yet have direct evidence for a functional consequence of such binding, they speculate that VH4-34 B cells may be playing a role in the opsonization and clearance of apoptotic cells in vivo.

Editorial Comments: Defining whether this occurs, whether there are instances in lupus where this process is abnormal, and if there is any association with a unique clinical phenotype are all very interesting questions. One might speculate that such autoreactivity would have a protective or mitigating effect in lupus, which might in the future be amenable to therapeutic manipulation.

Abstract 676 Lupus specific autoantigen nucleosome is preferentially released by UVB-induced apoptotic keratinocytes.
D Michel, V Abraham, P Cohen, and R Caricchio

In this abstract, Drs. Caricchio, Cohen and colleagues use a GFP-H2B fusion protein as a reporter to define the fate of nucleosomes in apoptosis in a series of stable cell lines from keratinocyte and lymphoid lineages. Apoptosis was induced with UVB irradiation or FasL exposure, respectively.

Results: The authors show that there were significant differences in the distribution of GFP-H2B in the different cell types, with the fluorescent protein being found in the cytoplasm and at the cell surface earlier in the keratinocyte line. The data suggest that keratinocytes are remarkably leaky in terms of autoantigens when compared with the lymphocyte line, and the authors speculate that this might have important implications for the understanding of photosensitive skin disease in SLE patients.

Editorial Comments: It will be important to define if such differences are observed also with endogenous antigens in primary cells. Regardless, the studies focus attention on potential differences in the immunogenic cell that drives lupus with different phenotypes.

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