No abstract

Human CD137 is a member of the tumor necrosis factor (TNF) receptor family and the homologue of murine 4-1BB. Recent studies have demonstrated that CD137 promotes accessory T cell activation, and regulates proliferation and survival of T lymphocytes. This study reports on the expression and function of CD137 in peripheral blood monocytes. While monocytes showed constitutive expression in 10 out of 18 healthy donors, CD137 was not expressed on resting T or B lymphocytes. Immobilized antibodies to CD137 markedly induced the production of IL-8 and TNF-alpha protein and mRNA, and led to inhibition of IL-10 expression by primary monocytes. Furthermore, cross-linking of CD137 on monocytes resulted in an increase of B lymphocyte apoptosis mediated by direct cell-cell contact of both cell populations. In conclusion, this study identified CD137 as a new receptor involved in monocyte activation by inducing a characteristic cytokine release profile. In addition, CD137 may play a role in monocyte-dependent control of B lymphocyte survival.

The tumor necrosis factor ␣ (TNF␣) inhibitors etanercept and infliximab have shown good clinical results in the treatment of rheumatoid arthritis and other autoimmune disorders. With these novel fusion proteins, immune-mediated side effects, among them various cutaneous reactions, have been encountered. We report herein the case of an erythema multiforme-like skin reaction to treatment with the monoclonal anti-TNF␣ antibody adalimumab in a patient with rheumatoid arthritis. The reaction occurred after the sixth injection and affected the palms and soles as well as the injection site. Discontinuation of the adalimumab therapy resulted in rapid improvement of the condition. Although this patient was receiving concomitant immunomodulatory therapy with methotrexate and leflunomide, these medications were not discontinued when the reaction developed, and no other potential pathogenetic mechanisms were identified. We believe the reaction is most likely attributable to adalimumab.

Gastrointestinal vasculitis in systemic lupus erythematosus (SLE) is quite rare and almost always accompanied by evidence of active disease in other organs, although occasionally it may be the presenting feature of the disease. Gastrointestinal involvement in SLE may present as lupus peritonitis, non-necrotizing pancreatitis, gastrointestinal vasculitis or surgical abdomen. Here we report a severe case of SLE which presented initially with fever of unknown origin. Severe distress, abdominal pain, the presence of occult blood in the stool and high acute-phase proteins were explained by a lupus peritonitis and intestinal vasculitis resembling inflammatory bowel disease. Whereas high-dose prednisone treatment did not prevent a severe relapse, we observed a sustained remission following i.v. cyclophosphamide pulse therapy. In the literature, only two similar cases are reported: one died despite a change in the therapy of a bowel perforation; our case was the second that improved under pulse cyclophosphamide. We suggest the use of cyclophosphamide after failure of steroids early in the course of SLE gastrointestinal vasculitis to prevent devastating complications.