[Surgical treatment of scapholunate ligament injuries: clinical and radiological results]. / Operative Therapie bei skapholunären Bandverletzungen: Klinische und radiologische Ergebnisse.

BACKGROUND: The purpose of this work was to retrospectively evaluate clinical and radiological results after surgical treatment for scapholunate ligament ruptures. MATERIALS AND METHODS: Measurements of range of motion, strength, and angles, as well as postoperative score assessments were performed in 32 patients. RESULTS: The average mobility in the operated wrist was 52° for flexion, extension 57°, radial 24°, ulnar deviation 31° and forearm rotation outward 88° and inward 89°. The recovery of force was 89% compared with the healthy hand. It showed an average skapholunar angle of 63°, a radioulnar angle of 22° and an average carpal height according to Nattrass of 1.49. Our patients rated the operation result with a median DASH score of 11 points (range 0-70.8 points). The median objective Mayo Wrist Score was 80 points (range 45-100 points). CONCLUSION: Surgical treatment of scapholunate ligament rupture, especially against the background of carpal collapse, is a very satisfactory method with very good results in the objective function and strength, and a high level of patient satisfaction.

Variability in the biological response to anti-CD20 B cell depletion in systemic lupus erythaematosus.

OBJECTIVE: To study the effects in systemic lupus erythaematosus (SLE) of B cell directed therapy with rituximab, a chimeric monoclonal antibody directed at CD20+ B cells, without concomitant immunosuppressive therapy in mild to moderate SLE. METHODS: Patients (n=24) with active SLE and failure of >or=1 immunosuppressive were recruited from three university centres into this phase I/II prospective open-label study. Patients were followed for 1 year to assess safety, efficacy and biological effects. RESULTS: In total, 18 of the patients scheduled to receive the full lymphoma dose of rituximab were evaluable for B cell levels in peripheral blood. Of these, 17 had effective CD19+ B cell depletion (<5 cells/microl). However, six of the depleted patients showed B cell return before 24 weeks. A total of 70% of patients improved by week 55, as defined by an SLE Disease Activity Index (SLEDAI) score improvement of >or=2 units from baseline. The degree of CD19+ B cell depletion was correlated with SLEDAI improvement at week 15 (r=0.84). In general, rituximab infusions were well tolerated. Approximately a third of the patients developed human anti-chimeric antibody (HACA) titres, which correlated with poor B cell depletion. Most patients (9 of 14) did not respond to immunisations with Pneumovax and tetanus toxoid. CONCLUSIONS: Rituximab is a promising new therapy for SLE. The variability of responses in patients with SLE may be related to HACA formation. The failure to respond to immunisations is surprising, in view of the apparently low risk of infections. Better biological markers are necessary to follow these patients during treatment.

Selective accumulation of related CD4+ T cell clones in the synovial fluid of patients with rheumatoid arthritis.

The role of T cells in the pathogenesis of rheumatoid arthritis (RA), especially in the perpetuation of advanced disease, remains unclear. Previous studies have focused on the TCR repertoire of synovial T cells in an attempt to determine whether the pattern of expression is characteristic of Ag-stimulated populations. However, the results of past studies have been conflicting. In the present work, we have undertaken an extensive analysis of the TCRs expressed by CD4+ T cells freshly isolated from synovial fluid of different joints and blood in three patients with established RA. Despite marked heterogeneity of synovial TCR expression, the results showed that 20 to 30% of the TCR beta-chain gene (TCRB) sequences found in one joint were also expressed in a second joint, but not in peripheral blood T cells of the same individual. Analysis of expressed TCRB complementarity-determining region 3 sequences showed the presence of multiple expanded clonal populations that were not predicted by quantitation of beta-chain variable region (Vbeta) expression by immunofluorescence staining. These studies also demonstrated sets of related, but different, complementarity-determining region 3 nucleotide sequences that encoded identical or highly homologous beta-chain amino acid sequences. Analysis of matching T cell clones derived from the joint by limiting dilution culture confirmed coexpression of highly homologous TCR alpha-chain gene (TCRA) and TCRB sequences. Together, these studies suggest that a significant proportion of synovial CD4+ T cells has been selected and expanded by conventional Ag(s) in this disease.

Antigen-binding repertoire and Ig H chain gene usage among B cell hybridomas from normal and autoimmune mice.

LPS-stimulated B cells were used to generate a panel of mAb that were a random sample of the preimmune repertoire of C57BL/6 and highly autoimmune, viable motheaten mice. These mAb were tested for reactivity to a number of "self" and foreign Ag. Binding that could be detected only at nM mAb concentrations or less was considered significant. We found that a surprisingly high number of the mAb bound one or more of the Ag tested, and many mAb bound more than a single Ag. Ag-induced mAb were likewise tested and found to have greatly reduced cross-reactivities. We found no significant differences, either in frequency of Ag binding or degree of cross-reactivity, between normal and autoimmune mice. Furthermore, the frequency with which a given Ag was bound by our panel of mAb was found to be proportional to the size of the Ag. The frequency with which individual VH gene families were expressed by our panel was consistent with a stochastic usage of VH genes in the preimmune repertoire. We interpret these data as showing that the preimmune repertoire is highly cross-reactive and that the activation of autoreactive clones in autoimmune animals is due to a defect in cellular regulation rather than a difference in repertoire.