Rheumatoid Arthritis: Braun M

Senolt L, Braun M, Vencovský J, Sedová L, Pavelka K. · Institute of Rheumatology, Charles University, First Medical Facility, Prague, Czech Republic. · Physiol Res. · Pubmed #17298211 links to  free full text

Abstract: Advanced glycation end-product (AGE) pentosidine has previously been demonstrated in different tissues and body fluids. It was suggested as a novel marker for evaluating the pathologic activity in rheumatoid arthritis (RA). In this study we analyzed the relation between pentosidine and markers of inflammation, cartilage turnover, immune response, and disease status of RA. Using HPLC, we analyzed pentosidine in serum and synovial fluid from 39 patients with RA and in serum from 38 healthy controls. Cartilage oligomeric matrix protein (COMP) and antibodies to CCP (anti-CCP) were measured by ELISA. Clinical disease status was assessed by Disease Activity Score 28 (DAS 28) and functional status by Health Assessment Questionnaire (HAQ). We demonstrated significantly higher serum levels of pentosidine in RA patients in comparison with controls. Pentosidine in serum significantly correlated with pentosidine in synovial fluid. Serum pentosidine levels were associated with erythrocyte sedimentation rate (p<0.03) but not with CRP, COMP, anti-CCP antibodies, DAS 28, or HAQ. In contrast to previous studies, we could not show any correlation of pentosidine levels with inflammatory status, clinical disease activity, markers of immune response, or cartilage breakdown. However, AGEs can be suggested as important players participating in joint destruction rather than markers of disease activity.

Senolt L, Braun M, Olejárová M, Forejtová S, Gatterová J, Pavelka K. · Institute of Rheumatology, Na Slupi 4, 12850 Prague 2, Czech Republic. · Ann Rheum Dis. · Pubmed #15897309 links to  free full text

Abstract: BACKGROUND: Pentosidine, an advanced glycation end product, increasingly accumulates in articular cartilage with age, and contributes to the pathogenesis of osteoarthritis (OA). Increased pentosidine concentrations are associated with inflammatory disorders-for example, rheumatoid arthritis. OBJECTIVE: To compare pentosidine serum concentrations in patients with knee OA and in healthy volunteers and to determine a relationship between pentosidine and cartilage oligomeric matrix protein (COMP)-a marker of articular cartilage destruction. METHODS: Paired serum and synovial fluid samples were obtained by arthrocentesis from 38 patients with knee OA and from 38 healthy volunteers. Pentosidine concentration was measured by reverse phase high performance liquid chromatography with fluorescent detection and COMP was determined by sandwich ELISA. RESULTS: Significantly increased serum pentosidine (p<0.01) and COMP (p<0.05) levels were detected in the patients with OA compared with the control group. Serum pentosidine correlated significantly with synovial fluid pentosidine (p<0.001). Pentosidine in synovial fluid (p<0.05) and in serum (p<0.05) correlated significantly with synovial fluid COMP. Pentosidine and COMP concentrations did not correlate significantly with the radiological stage of the disease. CONCLUSION: Increased pentosidine serum concentration in patients with OA and its correlation with the cartilage destruction marker COMP in synovial fluid suggests that pentosidine may be important in OA pathology and is a new potential OA marker.

Dohle J, Becker W, Braun M. · Orthopädische Klinik Volmarstein, Universität Witten/Herdecke, Wetter, Germany. · Z Orthop Ihre Grenzgeb. · Pubmed #11753773 No free full text.

Abstract: AIM: The purpose of this study was to identify typical radiological patterns of osseointegration following implantation of the Zweymüller-Alloclassic total hip system. METHOD: The follow-up included the clinical and radiological evaluation of 115 consecutive hips. For each case the screw direction of the cup was calculated individually to fully observe the bony surroundings by properly tilted X-ray beam. RESULTS: After 8.1 years, the Harris hip score was 88.5 points on average. Trabecular condensations leading toward the threads of the cup were observed in 100 cases, underlining the importance of the threads for load transfer. A complete intrusion of the threads into the pelvic bone was not accomplished in 23 cases with marked sclerosis of the acetabulum. The reduced connection, however, did not impair stability or function. The area of the distal stem is characterized by cortical hypertrophy and trabecular condensation of the neighbouring marrow. Linear radiolucencies were frequently observed in Gruen-Zone 1 and 7, in 5 cases extending into zone 2 and 6 without influence on the clinical function of the implant. CONCLUSION: Material and geometry of the Zweymüller total hip lead to a load transfer through the threads of the cup. The integration of the stem relies on cortical interlocking. Proximal linear radiolucencies do not impair function. The signs of osseointegration around the cup can be fully demonstrated only by a specially tilted X-ray beam at a right angle to the screw direction of the cup.

Estébanez-Perpiña E, Fuentes-Prior P, Belorgey D, Braun M, Kiefersauer R, Maskos K, Huber R, Rubin H, Bode W. · Abteilung für Strukturforschung, Max-Planck-Institut für Biochemie, Planegg-Martinsried, Germany. · Biol Chem. · Pubmed #11209755 No free full text.

Abstract: Granzyme B is the prototypic member of the granzymes, a family of trypsin-like serine proteinases localized in the dense cytoplasmic granules of activated natural killer cells and cytotoxic T lymphocytes. Granzyme B directly triggers apoptosis in target cells by activating the caspase pathway, and has been implicated in the etiology of rheumatoid arthritis. Human granzyme B expressed in a baculovirus system has been crystallized without inhibitor and its structure has been determined to 3.1 A resolution, after considerably improving the diffraction power of the crystals by controlled humidity changes. The granzyme B structure reveals an overall fold similar to that found in cathepsin G and human chymase. The guanidinium group of Arg226, anchored at the back of the S1-specificity pocket, can form a salt bridge with the P1-Asp side chain of a bound peptide substrate. The architecture of the substrate binding site of granzyme B appears to be designed to accommodate and cleave hexapeptides such as the sequence Ile-Glu-Thr-Asp-/Ser-Gly present in the activation site of pro-caspase-3, a proven physiological substrate of granzyme B. These granzyme B crystals, with fully accessible active sites, are well suited for soaking with small synthetic inhibitors that might be used for a treatment of chronic inflammatory disorders.

Illges H, Braun M, Peter HH, Melchers I. · Clinical Research Unit for Rheumatology, Albert-Ludwigs-University Medical Centre, Freiburg, Germany. · Clin Exp Immunol. · Pubmed #11091285 links to  free full text

Abstract: The expression of CR2 (CD21) by synovial B and T lymphocytes of patients suffering from various forms of arthritis was analysed with cytofluorometry and with reverse transcriptase-polymerase chain reaction. CR2 (CD21) cell surface protein was detected in normal quantities on peripheral B cells, but was almost absent on synovial B lymphocytes of the same patients. This reduction was most severe in patients with rheumatoid arthritis, but also observed in all other cases. CR2 (CD21) did not reappear after in vitro culture. CR2 (CD21) mRNA was also strongly reduced in synovial B and T lymphocytes. Synovial fluid B lymphocytes were larger than peripheral blood B lymphocytes, while T cells from the same patients showed no size differences. We conclude that synovial fluid B lymphocytes have undergone an irreversible step towards terminal differentiation. The presence or absence of CR2 (CD21) mRNA in peripheral versus synovial T cells indicates that CR2 (CD21) is also differentially expressed by T lymphocytes.