PubMed HealthSearch

Biomedical subjects

O J Mellbye

Publications and source records attributed to O J Mellbye.

At least 19 recordsLinked to original sources

TCR gamma/delta+ cell subsets in the synovial membranes of patients with rheumatoid arthritis and juvenile rheumatoid arthritis.

Using a peroxidase/anti-peroxidase immunohistochemical staining method, we examined sections of inflammatory synovial membranes from 13 patients with juvenile rheumatoid arthritis (JRA) and 11 with rheumatoid arthritis (RA). The relative numbers of TCR gamma/delta+ cells and the proportions of V delta 1+ and V delta 2+ subsets were recorded in the areas of the membranes most heavily infiltrated by CD3+ cells. In the JRA group, the majority (8/13) of the membranes had TCR gamma/delta+ cells which contributed between 5 and less than 10% of the total number of CD3+ cells. In the RA synovial membranes examined, 5/11 samples had between 5 and 10% TCR gamma/delta+ cells, but in another 5 TCR gamma/delta+ cells contributed to between 10 and 20% of CD3+ cells. No significant difference was noted between the two patient groups. However, the range of values found in the RA membranes appeared to be slightly higher in comparison to previously reported values for RA synovial fluid, peripheral blood and eluted synovial membrane T cells. Analysis of the relative proportions of the V delta 1+ and V delta 2+ subsets revealed a significant dominance of V delta 1+ cells in RA membranes and approximately equal numbers of the two populations in the JRA patients. As the majority of peripheral blood TCR gamma/delta+ cells use the V delta 2 segment this suggests a preferential homing or expansion of the V delta 1+ cells in both RA and JRA synovium. The overall distribution pattern of the TCR gamma/delta+ and V delta 1+ and V delta 2+ cells was also recorded. These cells mostly accumulated in the lymphoid-like tissues and in the perivascular area in the tissues of both RA and JRA patients. Occasionally, augmented numbers of these cells were found in the subsynovial layer or in the loose connective tissue. In the majority of cases, only a few TCR gamma/delta+ cells were located in the synovial layer. The function and the possible pathogenetic importance of these TCR gamma/delta+ cells have not so far been determined.

Adolescent

Demonstration of anti-rubella antibody-secreting cells in rheumatoid arthritis patients.

In the present study we describe a plaque-forming cell assay using erythrocytes coated with viral antigen, which detected anti-viral antibody-secreting cells against various viral antigens. These anti-viral antibody-secreting cell were studied in normal individuals with known viral infections and in rheumatoid arthritis patients. Rubella anti-viral antibody-secreting cells were present after induction in the peripheral blood of eight out of ten patients. No plaques were seen before induction. Synovial tissue of seven patients out of ten showed rubella-antigen-specific plaques before induction. In all three patients tested, the numbers of plaques increased after induction. The peripheral blood of only one patient showed plaque-forming cells against mumps virus and cytomegalovirus (CMV) antigen. No other patients showed any plaque against CMV, respiratory syncytial virus, mumps virus, measles virus, adenovirus, and varicella zoster virus antigens. The method appears to be promising in studying viral antibody-secreting cells in human immunopathology.

Antibodies, Viral

Lack of suppressor cell activity in rheumatoid synovial lymphocytes.

Lymphocytes were eluted from the synovial tissue of seventeen patients with rheumatoid arthritis (RA) and one with ankylosing spondylitis. In eight of these patients immunoglobulin production by synovial lymphocytes in the presence and absence of pokeweed mitogen was studied. In nine patients T lymphocytes were isolated from the eluted cells, and the T helper and suppressor cell functions were evaluated in an allogeneic co-culture system. Peripheral blood lymphocytes (PBL) from twenty-eight normal donors were also studied for comparison. Immunoglobulin produced by synovial lymphocytes was higher than in PBL of normal donors. However, the stimulation index of synovial tissue lymphocytes was lower. Most of the normal donors had suppressor cell activity in their peripheral blood, whereas in synovial tissue lymphocytes a statistically significant number of patients did not have any suppressor cell activity. In contrast, the synovial tissue lymphocytes showed helper activity not differing significantly from that of the T lymphocytes from peripheral blood of normal individuals.

Adolescent

Rheumatoid synovial lymphocytes lack concanavalin-A-activated suppressor cell activity.

Synovial lymphocytes eluted by enzyme treatment from eleven patients with rheumatoid arthritis (RA) were investigated for the presence of concanavalin A (Con A)-activated suppressor cell activity as compared with that of peripheral blood lymphocytes of twenty normal donors. In addition, two patients with psoriatic arthritis and juvenile rheumatoid arthritis (JRA) were also investigated. Synovial lymphocytes from the eleven RA patients showed a mean augmentation of 28 +/- 13.30, and thus clearly lacked suppressor activity, whereas the mean suppression in the lymphocytes from the twenty normal donors was 13 +/- 14.40. Synovial lymphocytes from one patient with JRA and one with psoriatic arthritis showed a normal suppressor activity.

Arthritis, Juvenile

Predominance of cells with T-markers in the lymphocytic infiltrates of synovial tissue in psoriatic arthritis.

Synovial tissue from 8 patients with psoriatic arthritis (PSA) were investigated by direct immunofluorescence technique with FITC-conjugated anti-F(ab')2 antiserum, and with a specific rabbit anti-human T-lymphocyte antiserum by indirect immunofluorescence method with FITC-conjugated goat-anti-rabbit Ig antiserum as the second layer. The majority of the lymphocytes in the tissue displayed membrane fluorescence with the anti-T antiserum. Staining with the conjugated anti-F(ab')2 antiserum revealed both intra- and extracellular immunoglobulins. These results indicate that the majority of the lymphocytes in the synovial tissue of PSA are T-lymphocytes, and that a minor number of the cells belong to the B-cell line.

Arthritis

Dermatomyositis associated with BCG vaccination.

Two young boys developed serious forms of dermatomyositis following BCG vaccination. Possibilities of a causal relationship between the disease and the vaccination are discussed. Extensive immunological tests, however, including in vitro stimulation of lymphocytes with PPD, gave no decisive evidence of abnormalities. It is concluded that in cases of dermatomyositis there is an absolute indication for a full anamnesis with regard to previous vaccination, to obtain clarification of the practical and theoretically important questions of a possible connection in this respect.

Adolescent

Glomerulonephritis in dermatitis herpetiformis. A case study.

A patient with dermatitis herpetiformis, proteinuria and reduced renal function is described. A renal biopsy studied by light and immunofluorescence microscopy revealed a glomerulonephritis with deposits of predominantly IgA and complement C3. Deposits of IgA and C3 were also demonstrated in a biopsy from normal skin, and a common pathway for the skin and renal lesions is suggested.

Complement C3

Effect of rat intestinal glycoprotein on complement lytic activity of 32P-labelled Escherichia coli.

Evidence for complement activation by an intestinal glycoprotein fraction from germfree rats is presented. The lowering effect on human serum bactericidal activity of E. coli was 28% for the intestinal glycoprotein fraction, 31% for zymosan, and 25% for inulin, while the lowering effect on conventional rat serum bactericidal activity was 65%, 53% and 21%, respectively. 32P-releasing activity of serum from germfree rats and from man on labelled E. coli amounted to 8% and 28%, respectively, of the release exerted by serum from conventional rats.

Animals

Complement activation during subsequent stages of canine endotoxin shock.

Changes in total haemolytic complement and levels of C3, C4 and C6 were studied during subsequent stages of lethal endotoxin shock in dogs. Substantial decreases of all parameters were observed. C4 and C6 decreases showed a very similar pattern, indicating activation of complement by the classical pathway in addition to the activation of the alternative pathway known to occur in this pathological condition. The findings emphasize the role of the complement system in the pathophysiology of endotoxin shock and are consistent with the concept that complement activation has prognostic value during endotoxaemia.

Animals

C-reactive protein and delayed hypersensitivity in juvenile rheumatoid arthritis.

In patients with juvenile rheumatoid arthritis (JRA), the delayed hypersensitivity found when skin-testing with a panel of memory antigens appeared to be reduced. Since C-reactive protein (CRP) has recently been shown to inhibit various parameters of cellular immunity in vitro, we tested the concentration of CRP in serum from 44 patients with JRA who had previously been tested for delayed hypersensitivity. The mean concentration of CRP in the patients was 32.2mg/l, while in age-and sex-matched controls it was less than 5 mg/l. By scatter diagrams and statistical analysis no association was found between the concentration of CRP and various expressions of delayed hypersensitivity in vivo.

Antigens

Local synovial synthesis of oligoclonal measles virus antibodies and of smooth muscle antibodies in a case of atypical rheumatoid arthritis.

A patient with atypical rheumatoid arthritis (RA) and local synovial synthesis of oligoclonal IgG in an arthritic knee joint is described. Measles virus-specific antibodies isolated from the synovial fluid (SF) were carried by oligoclonal IgG proteins but constituted only a fraction of the total oligoclonal IgG of the SF. Smooth muscle antibodies were markedly increased in the SF compared with the serum and were associated with an electrophoretically restricted fraction of IgG. The results indicate that a local synovial synthesis of measles virus-specific antibodies and of smooth muscle antibodies occurred within the affected joint in our patient.

Antibodies, Viral

Effect of penicillamine on complement in vitro and in vivo.

In most normal human sera the addition of penicillamine to a final concentration of 0-2 mmol/l and subsequent dialysis caused a slight reduction in serum haemolytic complement (CH50). At 200 mmol/l, CH50 activity was no longer demonstrable. Even high concentrations of penicillamine were needed to inhibit the ability of immunoglobulin to fix complement to preformed or forming immune complexes. This indicated that the reduction of CH50 observed in serum was due to an effect on the complement factors. In vivo, a dose of 240 mg penicillamine caused a slight transient reduction in CH50 in rabbit serum, while 1000 mg penicillamine had no effect on serum CH50 in patients with rheumatoid arthritis. In arthritis patients there was, however, some evidence for removal of complement deposits in synovial tissue during penicillamine treatment. Since it is theoretically possible that concentrations high enough to cause reduction of complement activity can be achieved locally in synovial tissue, the effect on complement may be one of the mechanisms by which penicillamine exerts its effect in rheumatoid arthritis.

Animals

Immunofluorescence studies for immunoglobulins and complement C3 in synovial joint membranes in psoriatic arthritis.

Synovial tissues from fifteen patients with psoriatic arthritis were investigated with direct immunofluorescence staining for immunoglobulins (IgG, IgA, and IgM) and from eigth patients for complement component C3. As control groups, there were synovial tissues from seven patients with seropositive rheumatoid arthritis and five patients with meniscal tears. In psoriatic arthritis, immunoglobulins were found in plasma cells in 93% of the cases, always with the presence of IgG (93%) but also with IgA (47%) and IgM (7%). C3 could not be demonstrated. In seropositive rheumatoid arthritis IgG was demonstrated in all patients (100%), often together with IgA (43%) and IgM (57%). C3 was found in all of these patients. In patients with meniscal tears neither immunoglobulins nor C3 could be found. The present findings indicate immunological activity in synovial membranes in psoriatic arthritis. The low amount of IgM and the lack of C3 suggest a difference compared to seropositive rheumatoid arthritis.

Arthritis

Deposition of fibrinogen (FR-antigen) in skin diseases. III. Synovial joint membranes in psoriatic arthritis.

Synovial joint membranes obtained by synovectomy in open bloodless fields were examined for FR-antigen (fibrinogen/fibrin-related antigen) in 15 patients with psoriatic arthritis (ps.a.) and in a control group of 5 patients with meniscal tears. All frozen and paraffin sections from ps.a. demonstrated FR-antigen at the synovial lining. In the tissue it was located at the surface and in cytoplasm of the superficial synovial cells. In the control group, FR-antigen was present in all frozen samples as a thin layer at the synovial lining surface, but absent in the paraffin sections. The presence of FR-antigen may contribute to the further development of the Inflammatory changes of the arthritis.

Antigens

A study of complement fixation by rheumatoid factor using a haemolytic assay system.

Complement fixation by rheumatoid factor (RF) in sera from rheumatoid arthritis patients has been investigated by means of a haemolytic assay system employing sheep erythrocytes (SRBC) coated with reduced and alkylated rabbit IgG anti-SRBC antibody. Haemolysis was almost invariably detected with RF-positive sera whereas haemolysis was not observed with RF-negative sera; It was evident from a marked increase in haemolysis, obtained following isolation of IgM-RF of high purity from several RF-positive sera, that the full in vitro complement-fixing ability and hence lytic potential of RF in serum is masked. Parallel observations were also made with synovial fluids. The inhibition of haemolysis by RF in sera and synovial fluids commonly involved a reduction in degree of lysis at high concentration of test material as well as a more generalized inhibition in overall percentage lysis. Complete replication of typical RF-positive serum and synovial fluid patterns of lysis on dilution was achieved by addition of heat-aggregated human IgG to isolated IgM-RF preparations and demonstrated that the two inhibitory effects are separable in terms of complement depletion and reduction of free rheumatoid factor antibody activity, respectively.

Arthritis, Rheumatoid

Complement and immunoglobulins in synovial fluid from synovectomized patients with rheumatoid arthritis.

In order to see if the complement (C) consumption and conversion, which are typical of rheumatoid joints, continue after synovectomy, 23 knee joints in which synovectomy had been performed from 4-5 to 6-5 years previously, were studied. The mean ratio of the concentration of C3, C4, and C5 in synovial fluid to that in palsma of the same patient was significantly lower than the corresponding ratio for the total protein content. This was found both in joints with active arthritis and in joints without clinical signs of arthritis, and in both seropositive and seronegative patients. Conversion products of C3 were found in 7 of the synovial fluids. The study thus indicated that the complement alterations in synovectomized joints are very similar to those in nonsynovectomized rheumatoid joints. In one synovial fluid agarose electrophoresis showed multiple sharp bands in the gamma region. By crossed immunoelectrophoresis some bands seemed to contain IgG with one type of light chains only. In plasma of the same patients the bands were much weaker, indicating local production of oligoclonal IgG in the joint.

Arthritis, Rheumatoid