Rainald Zeuner

Differential signaling by CpG DNA in DCs and B cells: not just TLR9

CpG-containing oligodeoxynucleotides (CpG ODNs) act on Toll-like receptor 9 (TLR9) that is expressed on B cells and plasmacytoid dendritic cells (pDCs) to stimulate the innate immune system, however, different types of CpG ODNs induce distinct responses. Recent papers suggest some CpG ODNs could require a second receptor or cofactor to signal. The different signaling complexes assembled might impact on the affinity with which CpG ODNs signal to TLR9 or activate additional pathways that lead to distinct immune responses.

IL-1RA in refractory systemic lupus erythematosus.

There is evidence from animal and human studies that IL-1 might play an important role in the development and maintainence of inflammation in systemic lupus erythemathosus (SLE). We hypothesized that, in SLE, there might be a relative deficiency in the physiologic antagonist of IL-1, IL-1 receptor antagonist (IL-1RA). We therefore treated three patients with active SLE in whom conventional therapy has failed with the human IL-1RA, Anakinra. In two of the three patients there was a transient effect on muscle pain and/or polyarthritis. In one patient with lupus myositis there was no effect at all. The therapy was well tolerated and the only significant side effect was a transient drop in complement levels (C3 and C4) without clinical or laboratory signs of increased SLE activity in all three patients.

Regulation of CpG-Induced Immune Activation by Suppressive Oligodeoxynucleotides

Abstract: Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated “CpG motifs” stimulate an innate immune response characterized by the production of cytokines, chemokines, and polyreactive Igs that promote host survival following infectious challenge. Yet CpG‐driven immune activation can have deleterious consequences, such as increasing the hosts susceptibility to autoimmune disease. The immunomodulatory activity of CpG DNA can be blocked by DNA containing “suppressive” motifs. This work explores the rules governing cellular recognition of stimulatory and suppressive motifs, and the resultant modulation of the immune system. Results suggest that both CpG and suppressive ODN may find use as therapeutic agents.

Biologics as treatment for systemic lupus: great efforts, sobering results, new challenges.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by specific organ manifestations and the production of autoantibodies to nuclear antigens. SLE can induce severe organ damage and carries the risk of fatal outcome. During recent years, no major progress has been made regarding new treatment options except for the introduction of mycophenolate mofetil. Therefore, the results of several large clinical trials using biological agents for treatment of SLE were hopefully awaited. Yet, the application of abatacept, belimumab and rituximab, respectively, to non-renal or renal lupus patients surprisingly has not been successful. Other studies using different agents have not been completed yet. Nevertheless, the results available so far will have a significant impact on the design of future clinical trials and will stimulate the debate on new targets for treatment of SLE.

C1qRP (CD93) expression on peripheral blood monocytes in patients with systemic lupus erythematosus

Aim of the study was to compare the expression of monocytes C1qRp (CD93) in patients with systemic lupus erythematosus (SLE) with that of healthy controls and to determine the influence of glucocorticoids and LPS on C1qRp expression. Thirty-six SLE patients and 20 healthy controls were analyzed by flow cytometry. Additionally, monocytes from five patients and five controls were cultured and stimulated with dexamethasone, interferon-γ and LPS, respectively, before the measurement of C1qRp expression. There was no difference in C1qRp expression between SLE and HC. SLE patients with no or only low dose steroids had a significantly higher C1qRp expression than those with higher doses. However, in vitro dexamethasone did not stimulate or down-regulate C1qRp expression. Upon LPS stimulation, C1qRp was significantly up regulated on monocytes both from patients and from controls. In conclusion, C1qRp expression and regulation was not altered in SLE patients. Possible relations with disease activity and medication need further investigations.