Acquired transient autoimmune reactions in Lyme arthritis: correlation between rheumatoid factor and disease activity.

Lyme spirochaetal disease (LSD) is a complex multisystem disorder which has been recognized as a separate entity due to its close geographic clustering of affected patients. The study aimed at evaluating the clinical and immunological features of LSD with chronic symptoms of meningoradiculitis, carditis and pauciarticular arthritis. Six patients with LSD and erosive arthritis who developed an increase of serum IgM rheumatoid factor (RF) which correlated with the inflammatory activity of the disease are described in detail. Besides raised IgG antibody titers to Borrelia burgdorferi (B. burgd.) antigen measured by ELISA technique, circulating immune complexes, antinuclear antibodies (ANA) and RF measured by laser nephelometric immunoassay were detected. Increased ANA and RF antibody rates suggest that LSD may closely be linked with transient autoimmune phenomena. Thus, in some cases, B. burgd. antigens might be able to produce a strong polyclonal B-cell stimulation, hence leading to an unspecific autoimmune reaction. But the question remains if transient unspecific autoimmune reactions actually take part in the pathogenesis of LSD.

Detection of granulocyte elastase specific IgG split products in rheumatoid synovial fluid.

In vitro granulocyte elastase is known to cleave a large number of substrates e.g. complement components, fibrinogen, collagen and IgG. In vivo the enzyme is rapidly complexed by the plasma inhibitors a1proteinase inhibitor (a1PI) and a2macroglobulin. Therefore in biological fluids elastase is measured as the inactive a1PI-complex. We present a radioimmunoassay for elastase specific IgG split products as marker for the elastase activity in vivo. Elastase splits human IgG1 in Fab and Fc fragments and low molecular weight peptides. We produced specific antibodies against the elastase induced Fc fragment by immunization with an elastase generated peptide. After purification of the antibodies there is no crossreactivity with native IgG nor with similar Fc fragments produced by plasmin or papain. The elastase specific IgG split products are detected in synovial fluid samples of patients with rheumatoid arthritis. The measured concentrations are higher in the RA group than in control groups of patients with other inflammatory joint diseases.

Neoantigenic group on Fc fragments in rheumatoid arthritis synovial fluids.

Expression of neoantigens during denaturation of IgG by oxygen radicals or proteolysis was assumed to be a possible mechanism for stimulation of rheumatoid factor (RF) formation and/or granulocyte dependent inflammative joint destruction. The so-called human leukocyte elastase (HLE) regularly released by stimulated neutrophils f.e. into the RA synovial fluid is known to split IgG in vitro into papain like fragments and low molecular weight peptides. The n-terminal site of the HLE related Fc is bearing a neoantigenic group which is located near the hinge region but not expressed by the native IgG. The neoantigen itself is represented by the low molecular weight peptides produced by prolonged HLE-IgG proteolysis. Detection of HLE generated Fc in synovial fluids was performed by radioimmunoassay specific for the neoantigen. Patients were divided into the three groups; I RA (n = 23), II inflammative joint effusions except RA (n = 23), III osteoarthritis and trauma (n = 19). The biological effect of the neoantigen on to granulocyte oxidative metabolism was tested by Cytochrome C reduction and chemiluminescence. Neoantigen bearing Fc could be detected in 15 of 23 cases of group I, in group II in 11 of 23 cases and only in 7 of 19 cases in group III. The median concentrations were 0.62 micrograms in group I and zero in II and III. The HLE derived Fc were able to inhibit the oxidative metabolism of activated granulocytes in vitro. The O2- production of stimulated granulocytes was depressed dose dependent by the neoantigen. The neoantigenic group itself does not react with RF as proved by nephelometric titration of HLE derived Fc, neoantigenic peptide and native IgG against a RF standard.

Intrasynovial orgotein therapy in rheumatoid arthritis.

30 patients with active classical rheumatoid arthritis affecting the knee took part in a 12-week double-blind trial in which intra-articular injections of orgotein (4 mg/week for 6 weeks) were compared with intra-articular aspirin 4 mg/week for 6 weeks. After 12 weeks clinical and biochemical assessments showed that orgotein was superior to aspirin. Clinical response was measured in terms of the cumulative rheumatoid activity index (RAI) which was based on scores for morning stiffness, range of flexion, pain and 25-foot (7.5 m) walking time. Treatment with orgotein resulted in significant improvement of the RAI; the improvement correlated with findings on knee-joint scanning which showed reduced mean uptake of 99mTc-pyrophosphate. After intra-articular orgotein injections, synovial fluid IgM and IgG rheumatoid factor levels fell significantly; so did prostaglandin E2 formation and lactate dehydrogenase activity. The changes in the synovial fluid suggest that the anti-inflammatory properties of orgotein may lie in its effect on proliferating synovia.

[Current aspects of rheumatoid arthritis]. / Aktuelle Aspekte der rheumatoiden Arthritis.

According to recent investigations two factors might play an essential role in the pathogenesis of rheumatoid arthritis (R.A.). Besides genetic components, i.e. the HLA-system and familial aggregation, the immune processes, mediating tissue inflammation and injury, are acknowledged as having established roles in the pathogenesis of R.A. The present report reemphasizes recent data concerning the autoimmunity and the immunologic network with trends of therapy in R.A. In view of the effectiveness of new nonsteroidal antiinflammatory drugs, a double-blind study of suxibuzon vs. indomethacin in 30 patients with active R.A. is described in detail. Both drugs were active and similar in their efficacy at 4 weeks as judged by clinical and laboratory measurements. No serious toxic side-effects were observed in both treatment regimens.

Levamisole-induced immunostimulation in spondylarthropathies.

The term "seronegative spondylarthritis" (S.S.A.) has been assigned to rheumatic disorders with closely related clinical features, defined by seronegativity and HLA-B27 phenotype. Its pathogenesis may be linked with a genetically controlled defective immune response. Therefore, 37 men with S.S.A. were treated with levamisole (150 mg/day, 3 days/wk) to stimulate the immune reactions. In a randomised controlled crossover study these patients also received a placebo; each period ran for 12 wk. Symptomatic therapy was continued through the entire 6 mo. Serious side-effects led to withdrawal of the active drug in 9 patients. Clinical response was measured in terms of a cumulative joint index, spondylometry, morning stiffness, and a pain scale. Treatment with levamisole resulted in a significant improvement in these parameters. Radiological evidence of sacroiliitis was present in 48.6% before and after levamisole, and joint scanning with 99Tc-pyrophosphate also revealed no progress in the disease. After levamisole treatment, IgM levels fell significantly (P less than 0-014). Likewise, the previously high percentage of antibodies with weak cytotoxic activity against lymphocytes was reduced after levamisole (P less than 0-049), and an increased rate of leucocyte-migration inhibition (L.M.I) was found in the levamisole-treated group. Thus, the immunostimulating properties of levamisole may interfere with defective immunoregulation in S.S.A. and, by improving the clinical conditions, lead to a change in the course of this disease.