Biomedical subjects
Publications and source records attributed to R B Clague.
Serum IgG antibody levels to native and denatured bovine type II collagen were elevated in 31.5 and 21.5% sera respectively from 200 American patients with RA. The prevalence of serum antibodies to native type II collagen is significantly higher than previously found in large studies of the prevalence of this autoantibody in Britain and Japan when using the same methodology.
Antibodies to native and denatured type II collagen were investigated in a group of 79 patients with rheumatoid arthritis (RA) of disease duration less than 12 months (median 8 months; range 3-12 months). Using a solid-phase ELISA to measure these antibodies, the incidence of patients with levels above the upper limit of normal (mean of normal plus 3 SD) was low as compared to previous findings in patients with established disease. The majority of positive sera contained small amounts of IgM antibodies to denatured type II collagen whilst a few had IgG antibodies to native and denatured type II collagen. These findings suggest that the production of high levels of serum anti-type II collagen antibodies in patients with RA is a secondary phenomenon, which may exacerbate the disease rather than be a primary cause of disease.
Specific circulating antibodies to the spiral gastric organism, Helicobacter pylori (HP) were detectable in 43% of 68 patients with rheumatoid arthritis by complement fixation test (CFT) and enzyme-linked immunosorbent assay (ELISA), a frequency comparable with that of a normal, age-matched population. Presence of these antibodies correlated strongly with a previous history of peptic ulcer disease (PUD) and to the severity of NSAID-related dyspeptic symptoms, the latter often leading to multiple drug intolerance. This contrasts with short term, prospective NSAID toxicity data, which show little relationship between ulceration and HP carriage. This result suggests, however, that HP may have a definite role in the pathogenesis of symptomatic PUD associated with more chronic NSAID usage, and may have important implications for ulcer prophylaxis in these patients.
A case of relapsing polychondritis (RPC) with strongly positive antibodies to both native and denatured type II collagen is reported. This is only the second report of the use of cyclosporin A in the treatment of RPC.
A cardinal feature of generalised nodal osteoarthritis is the loss of articular cartilage. To determine if autoimmunity to these cartilage collagens occurred, serum antibodies to native and denatured type II collagen were measured by enzyme linked immunosorbent assay (ELISA) in 96 patients (90 women, six men, aged 47-91 years) with generalised nodal osteoarthritis. Generalised nodal osteoarthritis was diagnosed by typical clinical and radiological features. Serum samples from 42 blood donors were assayed as controls. No significant difference was found between the patients with generalised nodal osteoarthritis and the controls. Furthermore, the 20 patients who were HLA-A1, B8 positive had similar antibody levels to the group as a whole. One woman patient with generalised nodal osteoarthritis (HLA-A1, B8 negative) had markedly increased antibody levels to native and denatured type II collagen in a pattern similar to that seen in patients with rheumatoid arthritis. This patient did not develop super added rheumatoid arthritis during a three year follow up period. Autoimmunity to type II collagen is therefore rare in generalised nodal osteoarthritis. A lack of collagen antibodies in a condition characterised by hyaline cartilage loss suggests that the presence of such antibodies in rheumatoid arthritis is more than a secondary event to joint damage.
Antibodies to denatured type II collagen were detected in the sera of a group of patients with rheumatoid arthritis by ELISA and by immunoblotting. The antibodies were further examined by immunoblotting against cyanogen-bromide derived peptides of type II collagen. The majority of sera reacted against only one or two peptides and antibodies to the CB-10 and CB-11 peptides were those most commonly found. However, some sera reacted with up to eight peptides, indicating that patients had antibodies to differing combinations of epitopes on type II collagen. Examination of sequential serum samples from an individual patient showed that there were changes in the class of antibody produced to type II collagen and that antibodies to different peptides were preferentially produced at different times in the course of the disease. Thus there was a selective response to different peptides of type II collagen not only between patients but also at different times in the course of disease in the same patient.
A 19-year-old man with cystic fibrosis developed arthritis at the age of 12 years. He also suffered from psoriasis, and was found to be HLA-B27 positive. His disease was episodic in nature for the first 5 years, but he later developed an unremitting erosive arthropathy which proved difficult to treat.
We describe a case of Wegener's granulomatosis in a lady who presented acutely with pulmonary haemorrhage, fever and breathlessness during her early pregnancy. She responded well to aggressive medical treatment.
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Antibodies to native and denatured collagens (types I, II, IX, and XI) were measured in sequential serum samples collected over 1.5-8.7 years (median 4.3) from 15 patients with rheumatoid arthritis. Eleven patients were seropositive and 4 were seronegative. Disease duration ranged from 3 years to 25 years before the first sample was tested. The patients showed a selective and varying response to collagens, even after disease had been present for a long time. Changes in the levels of antibody to one collagen type were not necessarily linked to changes in the levels of antibody to other collagens. Only some patients showed a strong correlation between C-reactive protein levels (a measure of disease activity) and antibodies to individual collagens. These findings suggest that rheumatoid arthritis patients produce antibodies to a wide variety of epitopes on these collagen molecules, as a result of different antigenic epitopes being exposed by cartilage degradation at different times throughout the disease.
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We describe a patient with longstanding rheumatoid arthritis (RA) who developed a monoarticular swelling of the left elbow which proved to be due to non-Hodgkin's lymphoma (NHL) infiltration of skin and subcutaneous tissue.
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Antigen specific and cross reacting antibodies to native and denatured types II and XI collagen were detected in the sera of rats immunised with either of these antigens. The antibodies from rats immunised with type XI collagen initially showed the strongest binding to the alpha 2(XI) chain of type XI collagen but later binding to the alpha 3(XI) chain was seen. Sera from patients with rheumatoid arthritis had antibodies that bound to both type II and XI collagens. Immunoblotting studies showed that most patients had antibodies which bound to the alpha 1(II) chain of type II collagen and to the alpha 3(XI) chain of type XI collagen. Some patients also had antibodies which bound to the alpha 1(XI) and to the alpha 2(XI) chains of type XI collagen. Thus antibodies to unique as well as to common epitopes on each of the two types of collagen molecule occur in some patients with rheumatoid arthritis.
In 81 patients with rheumatoid arthritis (RA) with antibodies to native type II collagen, the frequencies of each IgG subclass to native type II collagen were IgG1 (70%), IgG2 (12%), IgG3 (84%) and IgG4 (6%) and to denatured type II collagen were IgG1 (86%), IgG2 (23%), IgG3 (86%) and IgG4 (6%). Thus serum antibodies to type II collagen in patients with RA were predominantly of the complement fixing subclasses IgG1 and IgG3.
Fifteen patients on long-term haemodialysis were studied. Twelve patients were symptomatic and ten of these patients had shoulder pain. Eleven patients had associated carpal-tunnel syndrome. A statistically significant correlation was observed between the soft-tissue abnormalities of the hands, carpal-tunnel syndrome and the shoulder pain. Radiological changes were also common and were noted in 14 patients; cysts and erosions were the commonest. The shoulder joint was the most commonly involved joint. No obvious correlation existed with either raised parathormone or calcium levels. The possible role of beta 2-microglobulin and associated amyloidosis in the causation of this syndrome is discussed.
In rheumatoid arthritis the mean platelet volume does not alter with the institution of parenteral gold therapy and with long term gold therapy. It appears to have no value in predicting the onset of thrombocytopenia. It may, however, predict a haemorrhagic diathesis once gold induced thrombocytopenia is established.
The frequencies of antibodies to the cartilage type IX and XI collagens and to type I collagen were determined in 188 patients with rheumatoid arthritis, of whom 76 were positive for antibodies to native type II collagen. A higher proportion of patients with antibodies to native type II collagen had antibodies to these other collagens, but about one third of patients without antibodies to native type II collagen had antibodies to one or more denatured collagens. The patterns of antibodies present in individual sera suggested that there was a selective response to the collagens in an individual patient. The incidence of patients having antibodies to these native and denatured collagens in a random group of patients with rheumatoid arthritis was calculated.