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Biomedical subjects

O Wegelius

Publications and source records attributed to O Wegelius.

At least 19 recordsLinked to original sources

Class-specific rheumatoid factors, DR antigens, and amyloidosis in patients with rheumatoid arthritis.

Class-specific rheumatoid factors (RFs) were measured by enzyme immunoassay in 59 patients with rheumatoid arthritis complicated by systemic amyloidosis (RA+A), 47 patients with rheumatoid arthritis without amyloid (RA), 106 patients with other rheumatic diseases (juvenile rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome), and 55 blood donors. The patients with RA+A were characterised by a high prevalence of RF negativity; the IgM RF concentration was raised in only 18 of the 59 patients (31%, p less than 0.001 v RA), the IgG RF concentration in 20 of 59 (34%, p less than 0.001 v RA), and the IgA RF concentration in 24 of 59 (41%, p less than 0.001 v RA). A higher prevalence of HLA-DR4 (p less than 0.001) and a lower prevalence of DR2 (p less than 0.05) were found among 48 tested patients with RA+A when compared with a control panel consisting of 500 blood donors. No significant differences in the prevalence of DR1-DR7 or B27 antigens were observed, however, between patients with RA with or without amyloid.

Amyloidosis

Increased collagenase activity in human rheumatoid meniscus.

Collagenase activity of the knee joint menisci of patients suffering from rheumatoid arthritis was approximately 3-fold higher than that found in menisci of control patients. The mean collagenase activity in the macroscopically more diseased parts of the rheumatoid menisci was significantly higher than that in the less damaged areas. The specific degradation products resulting from the cleavage of human meniscoid type II collagen by rheumatoid meniscoid collagenase were demonstrated by SDS-polyacrylamide gel electrophoresis. Addition of N-ethylmaleimide, which activates latent mammalian collagenases, did not further increase collagenase activity in rheumatoid menisci. Thus in rheumatoid meniscus, collagenase may be synthesized and then activated, probably by proteolytic enzymes involved in the inflammatory reaction.

Arthritis, Rheumatoid

Primary amyloidosis with increased plasma carcinoembryonic antigen concentration. A case report.

A patient with suspected malignant disease had increased concentration of plasma carcinoembryonic antigen (CEA). Amyloidosis was demonstrated at autopsy. The amyloid fibril composition was characterized by immunohistochemical and immunochemical techniques and proved to be of the lambda light chain (AL) type. CEA was demonstrated in the liver parenchyma by using antihuman CEA antiserum. Increased plasma CEA concentration in a patient with primary amyloidosis has, to our knowledge, not been reported before.

Aged

Is amyloid A (AA) amyloidosis always secondary?

The case is reported of a patient with systemic AA amyloidosis associated with non-specific mesenteric lymphadenitis and chronic sideropenia. Renal, small bowel, and rectal biopsies showed amyloid deposits containing AA protein, as defined by potassium permanganate sensitivity and by reactivity with AA antiserum. Reversal of the nephrotic syndrome occurred during steroid-azathioprine therapy.

Adult

Clinical value of serum amyloid A and C-reactive protein measurements in secondary amyloidosis.

Serum amyloid A protein (SAA) and C-reactive protein (CRP) are acute-phase reactants synthesized by the liver. A close relationship was found between SAA and CRP concentrations in various rheumatic diseases (rs = 0.74 to 0.83). The serum concentration of these proteins reflected the activity of the rheumatic inflammation in a sensitive way. In secondary amyloidosis, persistently high SAA and CRP levels correlated closely with the progression of the renal amyloid manifestations. The findings show that measurements of SAA and CRP concentrations are valuable in assessing disease activity and the effect of therapy in rheumatic diseases, as well as in the assessment of the prognosis in secondary amyloidosis. Therapeutic measures that decrease SAA levels may reduce amyloid formation.

Amyloid

Enzyme-linked immunosorbent assays for antibodies to poly(A), poly dAT and histones: possibly useful tools for the evaluation of prognosis and disease activity in systemic lupus erythematosus.

In a prospective study 222 sera from 56 patients with systemic lupus erythematosus (SLE) were tested for antibodies to poly(A), poly dAT and histones using enzyme-linked immunosorbent assay (ELISA). Patients with active disease had significantly more often antibodies to poly(A), poly dAT and histones than patients with inactive disease. There was a positive correlation between the activity score of the disease and the levels of poly(A)-antibodies of IgG and IgM class, poly dAT-antibodies and antibodies to histones. Patients with SLE-nephritis had a higher level of poly dAT and IgG class poly(A) antibodies than patients without nephritis. Interestingly, patients with an SLE-nephritis had lower levels of IgM-poly(A)-antibodies than those without nephritis. Attempts to use the ELISAs in predicting the SLE exacerbations were unsuccessful. However, the assays can be used as parameters in the estimation of the disease activity.

Adolescent

DNA antibodies with and without complement-binding ability.

The relationship between immunoglobulin class and complement-binding ability of DNA antibodies was studied by indirect immunofluorescence and Crithidia luciliae (CL) as substrate in the sera of 28 patients with SLE and antibodies to CL-DNA. In 15 of 28 cases the antibodies bound complement and were IgG either alone or in combination with IgA and IgM. In the remaining 13 sera the antibodies were either IgA or IgM and did not bind complement. Only one of nine patients with nephritis had CL-DNA antibodies of IgM alone, whereas that was true for 10 of 19 patients without nephritis. The factors influencing the complement binding were further studied by using purified IgM rheumatoid factors. Their ability to 'mask' the IgG-type CL-DNA antibodies and to inhibit the binding of complement was confirmed. These findings suggest that complement activation in SLE does not occur in patients with IgM-type anti-ds-antibodies or in patients with rheumatoid factor activity.

Antibodies

Correlation of persistently high serum amyloid A protein and C-reactive protein concentrations with rapid progression of secondary amyloidosis.

The importance of serum amyloid A protein in the progression of renal failure was studied over three years in 28 patients with secondary (amyloid A type) amyloidosis predominantly due to rheumatoid arthritis. Creatinine clearance, the amount of protein in the urine, and serum amyloid A and C-reactive protein concentrations were determined regularly. Linear regression analysis showed a close correlation between the change in creatinine clearance each year and both serum amyloid A concentrations (20 patients: r= -0.83, p less than 0.001) and C-reactive protein concentrations (28 patients: r= -0.80, p less than 0.001). The correlation between serum amyloid A and C-reactive protein concentrations was also significant (317 parallel measurements: r=0.81, p less than 0.001). These findings suggest that monitoring serum amyloid A or C-reactive protein concentrations is valuable in assessing the prognosis in secondary amyloidosis and that therapeutic measures that lower serum amyloid A concentrations may reduce the formation of amyloid.

Amyloid

Lymphocyte infiltrations of the gastric mucosa in Sjögren's syndrome. An immunoperoxidase study using monoclonal antibodies in the avidin-biotin-peroxidase method.

Biopsy specimens of the gastric mucosa from 7 patients with primary or secondary Sjögren's syndrome were studied using the immunohistochemical avidin-biotin-peroxidase complex (ABC) method. Monoclonal antibodies (OKT series) were used as a primary layer to detect the surface antigens of various lymphocyte subsets in situ. Chronic inflammation with mononuclear cell infiltrates and/or glandular atrophy was seen in all 7 biopsy specimens. Immunohistochemical staining showed that the cell infiltrates consisted mainly of OKT3-positive T lymphocytes. In 1 patient plasma cells predominated at the sites of inflammation. Most of the T cells were OKT4-reactive lymphocytes, the OKT4/OKT8 ratio varying between 3 and 7. These findings from the gastric mucosa are in agreement with those obtained from the salivary glands of patients with Sjögren's syndrome and confirm the view that Sjögren's syndrome is a systemic disease affecting many organs, rather than a local disease restricted only to some exocrine glands.

Antibodies, Monoclonal

DNA antibodies and complement in SLE patients. A follow-up study.

Sixty-seven patients with systemic lupus erythematosus (SLE) were followed up for 3-19 months (mean 12) in a prospective study. The activity of SLE was estimated on clinical grounds and correlated with DNA antibody and complement levels. The disease reactivations consisted mostly of articular and cutaneous symptoms. There were 17 relapses and 22 complicating infections during the follow-up period. The levels of antibodies to native, double-stranded (ds) DNA (P less than 0.001) and antibodies to denatured, single-stranded (ss) DNA of IgG class (P less than 0.001) and C3 (P less than 0.001) correlated best with disease activity, which was estimated on the clinical symptoms and signs. These assays were not reliable, however, in predicting minor exacerbations. The levels of IgM class ss-DNA antibodies were significantly higher in SLE patients without nephritis than in SLE nephritis patients. In most cases, the combination of IgG class ss-DNA antibody and complement (C3 and CH50) determinations differentiated SLE relapse from infection.

Autoantibodies

alpha 1-Antitrypsin and reactive systemic amyloidosis.

1. Serum contains amyloid A-degrading activity. This activity is markedly reduced in patients with rheumatoid arthritis (RA) complicated by amyloidosis. alpha 1-Antitrypsin inhibits the degradative activity. To test the hypothesis that the activity of this enzyme is regulated by alpha 1-antitrypsin, we determined the concentrations, elastase-inhibitory activity and phenotypes of alpha 1-antitrypsin in 24 RA patients with and in 26 RA patients without amyloidosis. 2. alpha 1-Antitrypsin concentrations and biological activity were significantly increased in both patient groups compared with control subjects, but there was no difference between the two patient groups. 3. All patients who had developed amyloidosis were of the normal protease inhibitor (Pi) MM-phenotype. 4. We conclude that the difference in the amyloid A-degrading activity between RA patients with or without amyloidosis cannot be accounted for by differences in concentration, activity or Pi type of alpha 1-antitrypsin.

Adult

Predominantly vascular amyloid deposition in the kidney in patients with minimal or no proteinuria.

A series of nine patients with secondary (AA type) renal amyloidosis with little or no proteinuria is reported. Renal failure was the presenting sign of renal disease in seven patients. Renal biopsy revealed a predominantly vascular deposition of amyloid in all patients. Three patients had no glomerular amyloid deposits. This pattern of amyloid deposition was found in 12.5% of our renal biopsies from patient with amyloidosis. No significant clinical differences, other than the lack of proteinuria, were noted between these patients and patients with the usual pattern of amyloid deposition.

Adult

Reduced amyloid-A-degrading activity in serum in amyloidosis associated with rheumatoid arthritis.

The ability to degrade amyloid A fibrils was studied in the serum of 31 patients with amyloidosis associated with rheumatoid arthritis, 33 patients with rheumatoid arthritis without amyloidosis, and 47 healthy controls. Fibrillar amyloid A protein and the radial diffusion method were used. The mean degrading activity in serum was significantly lower in patients with rheumatoid arthritis complicated by amyloidosis (58 +/- 19% SD of the activity in a pooled sample of sera from 100 healthy blood donors used as standard) than in patients with rheumatoid arthritis alone (78 +/- 14%; p less than 0.001) or controls (99 +/- 19%; p less than 0.001). Alpha 1-antitrypsin, concentrations of which were raised in both groups of patients, inhibited the degrading activity in serum even in low concentrations. A negative correlation between degrading activity and alpha 1-antitrypsin concentrations was observed. These findings suggest that reduced amyloid-A-degrading activity is due to inhibition rather than to deficiency of enzyme.

Adult

Antibodies to SS-B in chronic inflammatory connective tissue diseases. Relationship with HLA-Dw2 and HLA-Dw3 antigens in primary Sjögren's syndrome.

SS-B antigen, purified from rabbit thymus, was used in an indirect enzyme immunoassay to demonstrate the presence of IgG-, IgA-, and IgM-type SS-B antibodies in sera from patients with well-defined and characterized chronic inflammatory connective tissue disease. High levels of antibodies to SS-B were found in patients with primary and secondary Sjögren's syndrome. Patients with Sjögren's syndrome secondary to systemic lupus erythematosus had significantly higher SS-B antibody values than patients with Sjögren's syndrome secondary to rheumatoid arthritis or patients with rheumatoid arthritis or systemic lupus erythematosus, alone. Two patients with rheumatoid arthritis without secondary Sjögren's syndrome also had a markedly elevated level of antibodies to SS-B. Antibodies of all immunoglobulin classes were found, although the highest values were either IgG- or IgM-type. In primary Sjögren's syndrome, antibody values to SS-B were higher in patients with HLA-Dw2 and/or HLA Dw3 than in those with other HLA-Dw types. We conclude that these antigens or specific immune-response genes close to the D region may be important for the development of antibodies to SS-B.

Antibodies

Serum pepsinogen I in rheumatic diseases. Reduced levels in Sjögren's syndrome.

Group I pepsinogens were measured by radioimmunoassay in the sera of 93 patients with rheumatic diseases and 99 controls. Patients with rheumatoid arthritis and systemic lupus erythematosus had levels of pepsinogen I similar to controls, whereas patients with Sjögren's syndrome had levels significantly lower than either controls (P less than 0.001) or patients with rheumatic diseases not associated with sicca syndrome (P less than 0.001). The concentrations of serum pepsinogen I were lower in patients with sicca syndrome alone than in those with sicca syndrome associated with some other connective tissue disease (P less than 0.05). In patients with Sjögren's syndrome, a negative correlation was found between serum concentrations of beta 2-microglobulin and pepsinogen I (r = -0.46, P less than 0.05).

Adult