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Introduction: Similar to matrix metalloproteinases, glycosidases also play a major role in cartilage degradation. Carbohydrate cleavage products, generated by these latter enzymes, are released from degrading cartilage during arthritis. Some of the cleavage products (such as hyaluronate oligosaccharides) have been shown to bind to Toll-like receptors and provide endogenous danger signals, while others (like N-acetyl glucosamine) are reported to have chondroprotective functions. In the current study for the first time we systematically investigated the expression of glycosidases within the joints., Methods: Expressions of beta-D-hexosaminidase, beta-D-glucuronidase, hyaluronidase, sperm adhesion molecule 1 and klotho genes were measured in synovial fibroblasts and synovial membrane samples of patients with rheumatoid arthritis and osteoarthritis by real-time PCR. beta-D-Glucuronidase, beta-D-glucosaminidase and beta-D-galactosaminidase activities were characterized using chromogenic or fluorogenic substrates. Synovial fibroblast-derived microvesicles were also tested for glycosidase activity., Results: According to our data, beta-D-hexosaminidase, beta-D-glucuronidase, hyaluronidase, and klotho are expressed in the synovial membrane. Hexosaminidase is the major glycosidase expressed within the joints, and it is primarily produced by synovial fibroblasts. HexA subunit gene, one of the two genes encoding for the alpha or the beta chains of hexosaminidase, was characterized by the strongest gene expression. It was followed by the expression of HexB subunit gene and the beta-D-glucuronidase gene, while the expression of hyaluronidase-1 gene and the klotho gene was rather low in both synovial fibroblasts and synovial membrane samples. Tumor growth factor-beta1 profoundly downregulated glycosidase expression in both rheumatoid arthritis and osteoarthritis derived synovial fibroblasts. In addition, expression of cartilage-degrading glycosidases was moderately downregulated by proinflammatory cytokines including TNFalpha, IL-1beta and IL-17., Conclusions: According to our present data, glycosidases expressed by synovial membranes and synovial fibroblasts are under negative regulation by some locally expressed cytokines both in rheumatoid arthritis and osteoarthritis. This does not exclude the possibility that these enzymes may contribute significantly to cartilage degradation in both joint diseases if acting in collaboration with the differentially upregulated proteases to deplete cartilage in glycosaminoglycans.

We describe a patient with therapy-resistant cutaneous T-cell lymphoma, Sézary syndrome variant, in association with concurrent polyarthritis and vitiligo, who was successfully treated with extracorporeal photochemotherapy (ECP). The combination of Sézary syndrome with seronegative rheumatoid arthritis is rare. In our patient the T-cell lymphoma was refractory to standard treatments that included psoralen-UVA, lymph node irradiation, and polychemotherapy. ECP has been shown to be effective in the treatment of selected cases of Sézary syndrome. There is a strong suggestion that ECP as a monotherapy can provide a significant benefit for other T-cell-mediated diseases including rheumatoid arthritis. In spite of a disease duration of 10 years, a very low CD8 cell count (2% of lymphocytes), a very high CD4 cell count (94%), and multiple unsuccessful chemotherapeutic trials before initiation of ECP, our patient achieved a long-lasting complete remission of both diseases with normalization of the CD4+ and CD8+ T-lymphocyte subsets. Concurrent developing vitiligo was unaffected by ECP.

In B-cell non-Hodgkin's lymphomas (NHL), clonal rearrangement of the immunoglobulin heavy chain (IgH) gene provides a useful marker for the detection of minimal residual disease (MRD) after treatment. To explore clinical usefulness of polymerase chain reaction (PCR) analysis of clonal IgH gene rearrangement in the detection of MRD a follow up study of 10 patients with B-cell NHL have been performed. At the time of diagnosis, tumor DNAs were PCR-amplified using sense primer specific for the heavy chain variable region (VH) and antisense primer specific for the heavy chain joining region (JH) of the IgH gene. The clonal rearrangement of IgH gene detected by PCR was used as clonal marker to determine MRD after treatment. In three cases, where clinical remission was not achieved, clonal IgH gene rearrangement was detected after the treatment. In seven cases, clinical remission was achieved after induction therapy but the PCR analysis revealed clonal IgH gene rearrangement in three of the cases. In all of the three cases, where MRD was detected by PCR, clinical relapse developed after 7-28 months of the therapy. In all cases that have relapsed, the IgH gene rearrangement was identical at the time of initial diagnosis and at the relapse. This study demonstrates that PCR analysis of clonal IgH gene rearrangement is a useful method to monitor and detect MRD before clinical relapse.

50 year old patient with advanced stage Sézary syndrome was treated with extracorporeal photochemotherapy. During extracorporeal photochemotherapy the photoactivable agent 8-methoxypsoralen was administered orally. After 2 h a leucocyte enriched blood fraction was irradiated with UVA extracorporeally and reinfused to the patient. Besides the extracorporeal photochemotherapy Prednisolone and Leukeran were administered. Slow but permanent improvement was observed, the erythroderma, pruritus disappeared, lymph nodes, liver, spleen enlargement reduced, the number of CD4 positive lymphocytes decreased, that of CD8 positive lymphocytes increased.

Plasma samples of patients with angioimmunoblastic lymphadenopathy (AIBL) were tested for anti-HTLV antibodies and for interferon content. Out of 12 patients 4 had antibodies to HTL-III. Two of these plasma samples contained antibodies reacting with HTLV-I and HTLV-II, too. Activated interferon (IFN) system was found in patients with clinical remission of AIBL, as it was detected by IFN titration in their plasma samples. Data suggest the etiological role in AIBL of virus(es) related to the HTLV family.