Penicillamine in rheumatoid arthritis.
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Biomedical subjects
Publications and source records attributed to R W Dorner.
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Rheumatoid nodules have been described in many children without evidence of clinical disease. These have been referred to as benign rheumatoid nodules (BRN). Except for one report, no serological abnormalities have been demonstrated. Four children with BRN have been studied. By means of a hemolytic assay, high titers of hidden rheumatoid factor (RF) have been found in the blood, i.e., 19S IgM RF detected after acid separation of IgM-containing fraction from the serum. The median hidden RF titer of the children with BRN was 1:362 and in healthy and disease controls was 1:7. The difference was significant at P less than 0.001. The results indicate that patients with BRN have active complement-fixing 19S IgM RF in their serum. Thus the association of hidden RF with BRN raises the possibility that the deposition of immune complexes (19S IgM-7S IgG) leads to small vessel vasculitis and nodular formation.
Fifteen to twenty percent of patients with juvenile rheumatoid arthritis (JRA) have positive latex fixation tests (LFT), whereas approximately 46% have previously been demonstrated to have hidden rheumatoid factors (RF), i.e., 19S IgM RF which can be detected by the LFT after acid separation of the IgM-containing fraction from serum. In this study, hidden RF were found in 59% of patients with seronegative JRA by use of a complement-dependent hemolytic assay. The median titer of JRA patients was 1:42, and in healthy and disease controls it was 1:7. The difference was significant at P less than 0.001. When data from patients with active disease were analyzed separately, the median titer for polyarticular JRA was 1:97 and for pauciarticular JRA, 1:91. The differences due to active disease were significant at P less than 0.001 and P less than 0.005, respectively. The results demonstrate that the hemolytic assay is more sensitive than the LFT in determining the presence of hidden RF, and activity of disease correlates well with high hemolytic RF titers.
Complement-fixing hidden 19S IgM rheumatoid factor (RF), i.e., 19S IgM RF that can be detected in the IgM-containing fraction by the hemolytic assay after separation of the serum by acid gel filtration, was evaluated serially (3 or more evaluations) over a 4-year period in 26 children with juvenile rheumatoid arthritis (JRA) correlating its presence with disease activity. Six children with continually active disease had consistently elevated hidden RF titers (26 evaluations), and the titers of 4 children with inactive disease remained insignificant (12 evaluations). Sixteen children had disease with variable activity over this period. Of these, 11 (43 evaluations) demonstrated positive correlation between disease activity and hidden RF titers. Five patients (8/20 evaluations) did not show correlation of disease activity with hidden RF titers. Thus, the presence of hidden RF correlated with disease activity in 93 of 101 evaluations. When hidden RF titers and the erythrocyte sedimentation rate were determined simultaneously on 40 occasions, the presence of hidden 19S IgM RF correlated significantly better (p less than 0.001) with disease activity.
It is proposed that the skin of scleroderma patients undergoes orderly temporal changes akin to connective tissue maturation which are reflected in its mucopolysaccharide composition. The apparently conflicting data on mucopolysaccharide changes in scleroderma skin reported in the literature are analyzed in the light of this hypothesis and a possible explanation for the conflict is profferred.
Fifty-three children with juvenile rheumatoid arthritis (JRA) were tested for immune complexes (IC) by 4 different methods, Clq solid-phase assay (ClqSPA), 2% polyethylene glycol precipitation assay (PEGPA), Raji cell assay (RCA), and the conglutinin assay (KA). Seventy-nine % of JRA patients demonstrated elevated IC levels by at least 1 method. Fifty-eight % of the JRA patients have elevated levels of IC by ClqSPA, 50% by the RCA, 37% by the KA, but 0% by the PEGPA. Seventy-four % of patients with polyarticular-onset, 88% of pauciarticular-onset, and 80% of systemic-onset JRA showed elevated levels of IC by at least 1 method. In the polyarticular-onset group, both in the rheumatoid factor (RF) positive (100%) and RF negative (64%) patients, and in the systemic-onset group (60%) the most elevated levels were demonstrated by the ClqSPA. The most elevated levels were found in the pauciarticular-onset type (69%) by the RCA. The presence of elevated levels of IC by the KA correlated with the presence of RF (p less than 0.01), hidden RF (p less than 0.05), and antinuclear antibodies (p less than 0.005). Elevated levels of IC detected by the ClqSPA correlated with the presence of RF (p less than 0.01), hidden RF (p less than 0.05), and active disease (p less than 0.01).
Synovial fluid (SF) of 16 adult patients with rheumatoid arthritis (RA) and 9 children with juvenile rheumatoid arthritis (JRA) was investigated for the presence of hidden 19S IgM rheumatoid factor (RF). SF was incubated with 500 IU hyaluronidase/g of SF, dialyzed against acetate buffers at decreasing pH, centrifuged and subjected to chromatography on a Sephadex G-200 column. The resulting IgM-containing fraction of SF from 5 seropositive patients (3 adult RA, 2 JRA patients) demonstrated RF activity by the complement-dependent hemolytic assay. Hidden 19S IgM RF was not found in the IgM-containing fractions of SF from 13 adult seronegative RA patients. Hidden 19S IgM RF was shown in the IgM-containing fraction of SF in 4 of 7 children with seronegative JRA.