Rheumatoid arthritis is genetically linked to major histocompatibility complex (MHC) molecules (HLA-DR4 and related molecules) and characterized pathologically by high levels of HLA-DR expression and infiltration of proliferative of synovial tissue with CD4+ T lymphocytes. T-lymphocyte activation is driven by specific signaling through polymorphic alpha/beta T-cell receptors (TCRs) that are reactive with antigen-MHC complexes present at the sites of inflammation. We are interested in characterizing rheumatoid TCRs molecularly to ascertain potential binding surfaces for antigen+MHC in synovial tissue. Accordingly, we have recently investigated the TCR alpha and beta chain heterogeneity in a series of 10 rheumatoid synovia obtained at the time of joint surgery. The most frequently detected V beta families were V beta 12, 14, and 17, each of which was found in 80% of specimens. We report here the molecular cloning and sequence analysis of 20 cloned V beta segments amplified with a V beta 14 family-specific TCR primer, and six cloned V beta segments amplified with a V beta 17 family-specific TCR primer from four rheumatoid synovia. Comparison with the data base revealed that these sequences belonged to the closely related V beta 3, V beta 14, and V beta 17 families. Dominant clones were apparent in two of the individuals by the presence of identical V-D-J regions, suggesting an antigen-driven process. Amino acid sequence analysis revealed a conserved motif in the putative fourth hypervariable region or CDR4. Molecular modeling of this epitope suggests that charged side chains are available for binding to ligand structures (e.g., antigen, MHC, or superantigen). We suggest this epitope may play a role in the molecular pathogenesis of rheumatoid arthritis.

Objective. We report a hypogammaglobulinemic patient with a destructive oligoarticular arthritis, whose synovial fluid cultures were repeatedly sterile.Methods and Results. We identified a Ureaplasma ureulyticurn infection in his affected joints, using a polymerase chain reaction (PCR) assay. Conclusion. The PCR technique promises to be extremely valuable in the rapid and specific diagnosis of infectious arthritis.Ureaplasma urealyticum, a mycoplasma organism which commonly colonizes the human urogenital tract, has been described as the cause of septic arthritis in several patients with hypogammaglobulinemia (14). However, this organism is difficult to isolate in culture and requires special culture media. We report a hypogammaglobulinemic patient with a destructive oligoarticular arthritis, in whom microbiologic cultures were sterile, but in whom a polymerase chain reaction (PCR) assay revealed the presence of U urealyticurn.Analysis of T cell receptor transcripts present in the synovium indicated a polyclonal population of T cells responding to this infection. CASE REPORTThe patient, a 27-year-old black man with the a-thalassemia trait and dysgammaglobulinemia, was admitted to the Hospital of the University of Pennsylvania for evaluation of persistent pain and swelling in the wrists and right ankle. He had. been healthy until the age of 14, when he began to have recurrent bouts of pneumonia. Serum imrnunoglobulin measurement showed an IgM level of 9.25 gm/ liter (normal 0.7-2.10) and undetectable IgG and IgA. Immunoglobulin deficiency with increased IgM was diagnosed, and the patient was treated with intermittent intravenous immunoglobulin therapy.At age 21 he began to experience pain and swelling of the right ankle and right shoulder. Shoulder roentgenograms revealed a destructive osteolysis of subchondral bone in the right humeral head. Subsequently, the right shoulder was surgically fused. Cultures for bacteria, rnycobacteria, and fungi, from material obtained at surgery, were sterile, and results of assays for rheumatoid factor were negative. Three months later, a surgical fusion of the left ankle was at-

While many investigators have examined V gene usage by the clonotypic T-cell receptor (TCR) in rheumatoid arthritis (RA) joints, few have reported on arthritic controls. We compared TCR alpha-chain V gene usage in knee synovial tissue specimens from 9 RA and 5 osteoarthritis (OA) patients. There was no significant difference in the number of V gene families used in RA compared with OA synovium. However, there was an increased prevalence of V alpha 28, V alpha 10, V alpha 17, and V alpha 18 and under representation of V alpha 15 in RA compared with OA synovium. Of these, V alpha 28 was also recently described by us as being present in RA synovial tissue early in the course of disease. V alpha 28 associated J region usage, and N-regional diversity was surveyed in T-cell receptors from additional rheumatoid synovial tissue T-cell populations and normal peripheral blood. Oligoclonality was observed in 6/10 rheumatoid specimens either by direct sequencing or where three or more molecular clones were sequenced, compared with 0/5 normal PBMCs. The oligoclonal populations included 2/3 cell lines stimulated with interleukin-2 (IL-2) alone. Several novel J regions were observed, with some recurrent residues observed at N-region positions. These data indicate an increased prevalence of certain TCR V region families in RA versus OA synovium, and suggest an antigen-driven expansion of V alpha 28-expressing T cells in RA synovium.