Alemtuzumab (CAMPATH 1H) Induction Therapy in Cadaveric Kidney Transplantation—Efficacy and Safety at Five Years

Alemtuzumab is a powerful lymphocyte depleting antibody currently being evaluated in solid organ transplantation. This paper describes 5-year results of a single center study of alemtuzumab as induction in renal transplantation. Thirty-three renal transplant recipients received 20 mg alemtuzumab on day 0 and 1, followed by half-dose cyclosporin monotherapy (trough concentration 75-125 ng/mL) from day 3. They were compared in a retrospective contemporaneous-controlled manner with 66 kidney transplant recipients transplanted in the same period and center who received conventional immunosuppression with cyclosporin, azathioprine and prednisolone. In the alemtuzumab group 12% of recipients died compared to 17% in the control group (p = 0.48); likewise graft loss was similar in both groups (21% vs. 26%, respectively, p = 0.58). Incidence of acute rejection was also comparable at 5 years (31.5% vs. 33.6%), although the pattern of rejection was different with 14% patients in the alemtuzumab group experiencing rejection over 1 year post-transplant compared to none in the control group. There was no significant difference between groups in terms of infection or serious adverse events. While acknowledging the limitations of a relatively small single-center study, results suggest that alemtuzumab induction allowed satisfactory long-term patient and graft survival equivalent to that seen with standard triple immunosuppression, while avoiding steroid therapy.     

Humanized monoclonal antibody treatment in rheumatoid arthritis.

A 41-year-old woman with active, seropositive erosive rheumatoid arthritis was treated with the humanized monoclonal antibody Campath 1H. She had not responded or developed side effects to myocrisin, sulfasalazine and penicillamine, and had not responded to inpatient bedrest and physiotherapy. There was a rapid clinical improvement within 24 hours of infusion, which was maintained for about 12-14 weeks after the infusion. The lymphocyte count was suppressed for 7 months after treatment. There were no significant side effects during or after treatment. No anti-Campath 1H response was detected. This preliminary study suggests humanized monoclonal antibody therapy may be of value in the treatment of rheumatoid arthritis.     

Inzidentalome der Nebenniere

Adrenal incidentalomas are clinically inapparent masses detected incidentally with imaging studies conducted for other reasons. They are relatively common and require structured diagnostic workup. In many cases surveillance is warranted. The diagnostic workflow has to reveal whether the mass is hormonally functioning and/or if there is evidence of malignancy. If the tumor is functionally silent and not larger than 4 cm, surveillance is warranted. Functioning tumors and masses larger than 6 cm have to be resected. Fine-needle aspiration biopsy is indicated in very rare cases, but pheochromocytoma has to be ruled out first.     

Characterization of the CAMPATH-1 (CDw52) antigen: biochemical analysis and cDNA cloning reveal an unusually small peptide backbone.

The CAMPATH-1 (CDw52) antigen has been purified from human spleen. The antigenic epitope is heat stable but sensitive to mild alkali treatment. Experiments with phosphatidylinositol-specific phospholipase C indicate that it is anchored by a glycosylphosphatidylinositol (GPI) anchor. An N-terminal sequence of 11 amino acids was determined, followed by an abrupt stop. Using short overlapping mixed oligonucleotide primers, cDNA synthesized from the mRNA of a human B cell line was amplified by the polymerase chain reaction. The product was used to isolate cDNA clones and the full amino acid sequence of the CAMPATH-1 antigen was deduced. It consists of 37 amino acid residues plus a 24-residue signal peptide. It has all the features expected for a GPI-anchored membrane protein except that the predicted mature protein is remarkably short, comprising no more than 18 residues and possibly as few as 12 (depending on the GPI linkage site). Potential attachment sites for carbohydrate are present and it is shown that the antigen contains N-linked oligosaccharide(s). This structure accounts for the known properties of the antigen, though the exact reasons why it is such a good target for cell lysis in vitro and in vivo are not yet clear.     

Effects of the immunomodulator diacetyl-splenopentin on antigen-induced arthritis in rabbits

Long-term treatment with the immunomodulator diacetyl-splenopentin reduces the severity of chronic joint inflammation and cartilage destruction in rabbits with antigen-induced arthritis. The level of specific antibodies as well as specific and non-specific cell-mediated immune reactivities including the proliferative response of spleen lymphocytes to cartilage proteoglycans in treated animals are lower than in untreated arthritic rabbits. Moreover, suppressor cell activity, which normally decreases during the early phase of inflammation, is enhanced and hyperreactive helper cell potential is reduced. These findings suggest that treatment with diacetyl-splenopentin normalizes the immune regulation, which is disturbed in the early phase of inflammation. This might result in a depression of the hyperreactive immune system including the autoimmunity developed against cartilage. Lowered immune reactivity in the joint in turn reduces the severity of chronic joint inflammation.Preliminary results were presented at the 6th Halle Summer Colloquium on Modulation, Mediation and Inhibition of Inflammation (H. Bekemeier and R. Hirschelmann, eds.). Wiss. Beitr. Martin-Luther-Universität Halle-Wittenberg 1987/7. Halle (Saale) 1987.     

Campath-1M--prophylactic use after kidney transplantation. A randomized controlled clinical trial

Campath-1M is a rat monoclonal IgM antibody that binds human complement and recognizes virtually all peripheral human mononuclear cells. It is known to be effective in T cell depletion of bone marrow grafts, and encouraging results were obtained in a pilot study in which the antibody was used in prevention and treatment of rejection of kidney, pancreas, and liver allografts. In this randomized controlled clinical trial, Campath-1M has been evaluated as a prophylactic agent following renal allografting. It is shown that patients who received a 10-day course of the antibody immediately postoperatively, in addition to standard therapy with high-dose cyclosporine (17 mg/kg), experienced a significantly lower incidence of early acute cellular rejection than control patients who received cyclosporine alone. There was no evidence of "rebound" rejection following the end of antibody treatment to suggest that rejection had merely been delayed. However, patients who received this additional immunosuppression experienced a significantly higher incidence of serious infections than controls, this negating any benefit from the treatment in terms of graft survival. Thus, a monoclonal antibody of broad specificity directed against lymphocytes may be effective as a prophylactic agent after organ transplantation but its use should be accompanied by a reduction in other immunosuppressive drugs.     

Do L3T4+ T cells act as effector cells in protection against influenza virus infection

This study aimed to analyse the roles of Lyt 2+ and L3T4+ memory T-cell subpopulations in murine influenza infection. Previous work has shown that Lyt 2+ cytotoxic T-cell (Tc) clones can adoptively transfer protection. We therefore wished to see whether L3T4+ (Th) cells could also act as protective effector cells. Donors for adoptive cell transfer were thymectomized mice, depleted in vivo of either Lyt 2+ or L3T4+ T cells with monoclonal antibodies (MAb) and then infected with influenza virus (A/X31). Primed spleen cells, after removal of the B cells, were transferred into irradiated hosts infected simultaneously or persistently with a heterologous influenza virus and the effect on lung virus replication determined. Depletion of L3T4+ T cells suppressed the formation of IgG antibodies after influenza virus infection, indicating significant depletion of T-helper function. Yet Lyt 2+ class I MHC-restricted Tc cells were effectively primed in these mice, albeit to half the normal level. Adoptive transfer of the Lyt 2+ memory T cells cleared virus in a persistent infection within 6 days. Spleen cells selected for L3T4+ T cells cleared virus within 21 days of transfer in a simultaneous infection and reduced viral titres in a persistent infection, but not as effectively as L3T4+-depleted spleen cells. Although no Lyt 2+ cells were detected by fluorescence staining in Lyt 2+-depleted spleens, we could detect low levels of class I MHC-restricted influenza-specific Tc memory cells in host spleens following influenza infection. Therefore, whether the early viral clearance is solely due to L3T4+ T cells is not clear. Lyt 2+ memory T cells appear more efficient in this respect than L3T4+ memory T cells.