F. C. Breedveld

SYNOVIAL FLUID T CELL REACTIVITY AGAINST 65 kD HEAT SHOCK PROTEIN OF MYCOBACTERIA IN EARLY CHRONIC ARTHRITIS

The in vitro proliferative response against a recombinant 65 kD Mycobacterium bovis protein that has 100% homology with the 65 kD protein of M tuberculosis was tested in synovial fluid and peripheral blood mononuclear cells from patients with rheumatoid arthritis (RA) and other types of chronic arthritis. An acetone precipitate (AP) of M tuberculosis, and a purified protein derivative (PPD) of M tuberculosis were also tested. Responsiveness of synovial fluid lymphocytes to the mycobacterial antigens was found both in patients with RA and in patients with other forms of chronic inflammatory arthritis, but not among controls. T cell reactivity against mycobacterial antigens was nearly always higher in synovial fluid than in peripheral blood in those patients who showed reactivity. A significant association was found between responsiveness of synovial T cells to the 65 kD protein and AP, but no relation between responsiveness to the 65 kD protein and PPD. Both the number of 65 kD protein responders and the mean proliferative response of synovial T cells to the 65 kD protein were inversely correlated with duration of joint inflammation. Thus, a 65 kD-protein-specific reactivity of synovial T cells, mainly present in an early stage of joint inflammation, may be responsible for triggering chronic arthritis.

An open study of pentoxyfylline and thalidomide as adjuvant therapy in the treatment of rheumatoid arthritis.

OBJECTIVE: Dysregulation of tumour necrosis factor alpha (TNF alpha) production is thought to be important in rheumatoid arthritis. Since pentoxifylline and thalidomide inhibit endotoxin induced TNF production in vitro, these drugs were tested in an open study in rheumatoid arthritis patients to assess toxicity, the effect on TNF production, and the antiarthritic effects. METHODS: 12 patients with active rheumatoid arthritis were treated with 1200 mg pentoxifylline and 100 mg thalidomide a day during 12 weeks. In addition, TNF production was assessed by ex vivo whole blood cultures stimulated with endotoxin. RESULTS: Adverse events such as xerostomia, drowsiness, and constipation occurred in almost all patients, which led to discontinuation in three. The drugs halved the TNF production capacity during treatment (ANOVA, P < 0.03) whereas production capacity of interleukin (IL) 6, IL-10, and IL-12 was not affected. Of the nine patients who completed the study, five fulfilled the ACR-20% response criteria after 12 weeks of treatment. CONCLUSIONS: Although pentoxifylline/thalidomide reduced the production capacity of TNF, the benefit/side effects ratio was poor due to multiple adverse effects, while clinical observation suggests limited efficacy.

99Tcm-labelled polyclonal human immunoglobulin G scintigraphy before and after intra-articular knee injection of triamcinolone hexacetonide in patients with rheumatoid arthritis.

The ability of 99Tcm-labelled polyclonal human immunoglobulin G (99Tcm-IgG) scintigraphy to monitor intra-individual variation in arthritis activity was studied in seven patients with rheumatoid arthritis (RA). These patients were treated with an intra-articular injection of 20 mg triamcinolone hexacetonide. The results of semiquantitative 99Tcm-IgG scintigraphy were compared with the degree of joint swelling and the histological changes observed in synovial biopsies before and 14 days after the injection. In all seven patients the local treatment resulted in a decreased arthritis activity of the treated knee as measured clinically or histologically. This decrease was parallelled, in all patients except one, by a lower uptake of 99Tcm-IgG after the injection when compared to uptake prior to treatment. This study shows that 99Tcm-IgG scintigraphy is able to reflect intra-individual variations in arthritis activity in patients with RA.

Value of 99mTc-IgG scintigraphy in the prediction of joint destruction in patients with rheumatoid arthritis of recent onset.

The ability of technetium-99m-labelled polyclonal human immunoglobulin G (99mTc-IgG) scintigraphy to predict joint destruction in patients with rheumatoid arthritis (RA) was investigated in this study. The progression of radiographically determined joint destruction in wrists, hands and feet was compared with the results of physical and laboratory examination, as well as 99mTc-IgG scintigraphy, measured at the beginning of a year-long study on 30 patients with RA of recent onset. The sensitivity of joint swelling in predicting the progression of radiographically determined joint destruction ranged between 57% and 74%. The sensitivity of 99mTc-IgG scintigraphy ranged between 71% and 100%. The specificity and positive predictive value both of joint swelling and 99mTc-IgG scintigraphy were low. Multiple regression analysis showed that for the total joint score, and for the metacarpophalangeal and forefeet joints, progression of radiographically determined joint destruction was primarily predicted by 99mTc-IgG scintigraphy. Joint swelling, ESR and IgM rheumatoid factor did not contribute to this prediction. We concluded that 99mTc-IgG scintigraphy is superior to conventional clinical and laboratory measurements in RA with respect to prediction of joint destruction.