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Biomedical subjects

T Helve

Publications and source records attributed to T Helve.

At least 19 recordsLinked to original sources

Serum hyaluronate level as a predictor of radiologic progression in early rheumatoid arthritis.

Increased serum levels of hyaluronate (HA) have been found in patients with rheumatoid arthritis (RA). This probably reflects increased leakage of HA from the inflamed joints into the circulation. In a prospective study of 40 patients with early RA, we evaluated the relationship of serum HA to clinical, laboratory, and radiologic parameters of disease activity. The patients were followed for 12 months; all had active disease at study entry. We confirmed the previous finding of higher serum HA concentrations in RA patients compared with healthy controls. At study entry, the patients' serum HA levels correlated positively with clinical and laboratory parameters of acute inflammation. Despite marked clinical improvement during therapy with second-line drugs, the serum HA levels increased during the followup period. At the end of 1 year, these levels correlated with the radiologic progression of joint lesions, whereas they showed a less pronounced correlation with clinical or laboratory parameters of inflammation. We conclude that, in early RA, serum HA levels may reflect ongoing joint destruction and may even predict subsequent joint damage.

Adult

Outcome of systemic lupus erythematosus. A study of 66 patients over 7 years with special reference to the predictive value of anti-DNA antibody determinations.

A cohort of 66 patients with SLE that were thoroughly studied, both clinically and serologically in 1980-81, when they had a mean disease duration of eight years, were evaluated seven years later in order to assess the long-range outcome of the disease. Five patients were lost from follow-up and 12 (20%) died during the follow-up. The estimated 10-year survival was 91%. A total of 30 patients (45%), showed no signs of nephritis at any stage, and in only eight an active nephritis was found during the follow-up. The previous antibody determinations, provided no predictive information regarding the behaviour of the renal manifestations. Arthralgia was the main clinical symptom during the follow-up. Hypertension developed in 23%. At the end of the follow-up the disease was regarded as active in 13% of the patients.

Adolescent

Cellular fibronectin in rheumatoid synovium and synovial fluid: a possible factor contributing to lymphocytic infiltration.

Mouse monoclonal antibodies against ED sequence-containing cellular fibronectin (cFn) were used to show that Fn in the inflamed synovium is distinct from the major form of plasma Fn (pFn). An accumulation of cFn was seen at sites of hyperplasia of the rheumatoid synovial membrane and in the walls of small vessels in the synovium by immunofluorescence microscopy. cFn was also found in rheumatoid synovial fluid by immunoblotting. Approximately one-fifth of the T lymphocytes from rheumatoid synovial fluid bound to Fn. The binding of synovial fluid T cells was always higher than that from peripheral blood. These results have two implications. On the one hand, the cellular type of Fn may be an indicator of synovial inflammation. On the other hand, the deposition of Fn may be a factor contributing to the infiltration of mononuclear cells into the synovium.

Animals

Autoantibody activity of cryoglobulins and sera in systemic lupus erythematosus. Association of IgM class rheumatoid factors with Raynaud's syndrome.

A total of 218 samples obtained during a follow-up study of 36 patients with systemic lupus erythematosus (SLE) were tested for the presence of cryoglobulins. Cold-insoluble precipitates were found in 81% for the patients (29 patients, 114 samples). The protein concentration of the cryoglobulins correlated significantly with the disease activity. Autoantibody activity was determined in the dissolved cryoglobulins and in corresponding serum samples by enzyme-linked immunosorbent assays (ELISA). IgM-RF could be demonstrated more often in the cryoglobulins than in the sera (75% vs. 14%), whereas IgA-RF were seen in 28% of both cryoglobulins and sera. Anti-ssDNA and anti-poly(A) antibodies of both IgG and IgM classes were found more often in the sera than in the corresponding cryoprecipitates. In 7 samples from 5 patients an increase in the IgG-anti-ssDNA activity was seen after DNase digestion of the cryoglobulins. Patients with Raynaud's syndrome had a significantly higher level of cryoprecipitating IgM class rheumatoid factors than other patients. There was also an association between the IgG-anti-poly(A) antibody levels in the cryoglobulins and the activity of the disease. There was no difference with regard to the composition of the cryoglobulins, between patients with nephritis and those without an overt renal disease. Thus, the presence of cryoglobulins in SLE indicates active disease, but not necessarily renal involvement. IgM rheumatoid factors may play a role in the pathogenesis of Raynaud's syndrome of SLE patients.

Adult

Screening test for rheumatic diseases: a combined enzyme immunoassay of rheumatoid factors and antibodies to DNA and extractable nuclear antigens.

Three hundred and one sera from patients with rheumatic and other diseases were investigated using a simple enzyme immunoassay for screening of rheumatoid factors and antinuclear antibodies. The assay had a sensitivity of 77% for systemic lupus erythematosus, 90% for the primary sicca syndrome, and 89% for rheumatoid arthritis. Only 13% of sera from patients with chronic non-rheumatic diseases were positive. The test was further evaluated in a group of patients with suspected rheumatic disease who were followed up for six to 12 months. The test was positive in 16 of 17 sera from patients with connective tissue diseases but in only seven of 36 sera (19%) from patients with non-inflammatory joint diseases. None of the four patients with reactive arthritis was positive by this test. The sensitivity of the assay was comparable with that of the agglutination and immunofluorescence tests for rheumatoid factors and antinuclear factors. For the screening of rheumatoid factor and antinuclear antibodies this kind of test panel offers a simple alternative to the conventional tests for small clinical laboratories and for those in which the autoantibody tests could be automated, as the assay can be performed in one working day and only one dilution of serum is needed to obtain a quantitative result.

Adolescent

Anti-DNA antibodies of IgA class in patients with systemic lupus erythematosus.

Sera obtained from 53 patients with systemic lupus erythematosus (SLE) were investigated for the presence of immunoglobulin class-specific antibodies against native (ds)DNA and denatured (ss)DNA. The methods employed were the Crithidia luciliae test and an enzyme-linked immunosorbent assay (ELISA), respectively. Anti-dsDNA antibodies of IgG class were seen in 42%, IgM-anti-dsDNA antibodies in 43%, and IgA-anti-dsDNA antibodies in 30% of the patients. There was an association between the presence of both IgG- and IgA anti-dsDNA antibodies and the activity of the disease. Patients with active nephritis also had anti-dsDNA antibodies of IgG and IgA class significantly more often than patients with inactive nephritis or without renal disease. IgG-anti-ssDNA antibodies were seen in 89%, IgM-anti-ssDNA antibodies in 51%, and IgA-anti-ssDNA antibodies in 66% of the patients. Patients with nephritis had low levels of antibodies to ssDNA of IgM class. We suggest that immunoglobulin class-specific anti-DNA antibodies should be determined in the diagnosis and monitoring of SLE.

Adult

Neurofilament antibodies in systemic lupus erythematosus.

Autoantibodies against neuronal antigens occur in sera of patients with systemic lupus erythematosus (SLE). These antibodies may have significance in the pathogenesis of neurological complications of SLE. However, the neuronal structures containing the corresponding autoantigens are poorly known. In our study we assayed circulating antibodies against defined neuronal components--neurofilaments--by an enzyme-linked immunosorbent assay (ELISA) using purified neurofilament polypeptides as targets. Circulating neurofilament antibodies (anti-NF) of IgG class were detected in 21% of 28 patients with SLE and in 6% of 17 patients with rheumatoid arthritis and in none of the 14 patients with primary sicca syndrome and 40 blood donors. The presence of anti-NF could also be confirmed by the indirect immunofluorescence technique using frozen sections of rat spinal cord. In one serum, anti-NF cross reacted with vimentin type of intermediate filaments. The antibodies bound both to the 70 kilodalton and the 200 kilodalton polypeptides of neurofilaments as judged by the immunoblotting technique. Two of 6 anti-NF positive patients had neurological complications.

Animals

Prevalence and mortality rates of systemic lupus erythematosus and causes of death in SLE patients in Finland.

Nationwide prevalence and mortality rates in systemic lupus erythematosus (SLE) were estimated using a computer file of all hospital discharge records and cause of death statistics from 1972 to 1978. Age-specific and sex-specific prevalence rates obtained from 1976 to 1978 and mortality rates from 1972 to 1978. In December 1978 the prevalence of SLE was 28:100 000. The overall mortality rate was 4.7 per million person-years in 1972-78. Active lupus nephritis, vascular events and infections were the most frequent causes of death in SLE patients.

Adolescent

Profiles of antibodies to histones, DNA and IgG in patients with systemic rheumatic diseases determined by ELISA.

The occurrence of antibodies against the total histone complex and the histone fraction H1, antibodies against denatured (ss) DNA and the synthetic double stranded polynucleotide poly dAT, as well as rheumatoid factors (RF) was determined in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) using enzyme linked immunosorbent assays (ELISA). Antihistone antibodies could be demonstrated at a frequency of about 17% in the patients with systemic rheumatic disease with no differences between the groups, even if there was a tendency for anti-H1 antibodies to occur more often in the SLE and SS patients than in the RA patients. Some of the antihistone antibody activity seen in the RA patients seems to be due to crossreactive RF. All patient groups showed significant IgG anti-ssDNA antibody activity compared to the controls, but the highest antibody levels were seen in the SLE patients. IgG antipoly dAT antibodies occurred significantly more often and at higher levels in the SLE patients than in the other patient groups. Although the individual tests did not readily distinguish the 3 diseases from each other, the antibody profiles were different. Patients with SS had the broadest reactivity, and the SLE patients had antibodies predominantly restricted to polynucleotides.

Adult

Nuclear matrix antibodies in rheumatic diseases.

We describe a new type of human antinuclear antibody (ANA) reacting with the nuclear matrix by indirect immunofluorescence technique. Cultured cells of human and animal origin were used as substrate. Before assay, cells were extracted with buffers to remove other components of the nuclei leaving the matrix intact. Two types of immunofluorescence staining patterns were seen: homogenous and speckled. When human embryonic fibroblasts were used as targets, sera from patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) contained significantly more nuclear matrix antibodies of the homogenous type than the control group. These antibodies were often, especially in SLE, species cross-reacting. (When PTK-2 cells were used as substrate the difference between SLE and RA was also significant [60 vs 8%]). Antibodies with speckled staining pattern were seen only in the patient sera. Their highest incidence (35%) was found in sera from patients with the primary sicca syndrome. The nuclear matrix may be a major target for ANA in rheumatic diseases.

Antibodies, Antinuclear

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

Transformation of membranous glomerulonephritis into crescentic glomerulonephritis with glomerular basement membrane antibodies. Serial determinations of anti-GBM before the transformation.

This case report describes a patient who initially had a pleuritis and arthalgias. During the follow-up he developed first a membranous glomerulonephritis with nephrotic syndrome and subsequently a crescentic, rapidly progressive glomerulonephritis with glomerular basement membrane antibodies (anti-GBM). An analysis of the serum samples obtained during the follow-up revealed no infections at the onset of renal failure. However, anti-GBM could be demonstrated in the serum samples obtained 2 months before the deterioration of the renal function. The anti-GBM did not react with alveolar BM and the patient had no signs of pulmonary hemorrhage. The etiology and the sequence of the pathological events of rapidly progressive glomerulonephritis is discussed in the light of these observations.

Autoantibodies

Salivary gland involvement in systemic lupus erythematosus. A sialographic study.

Hydrostatic parotid sialography was performed in 46 rheumatological patients, 17 of whom were SLE patients. Signs of atrophy of the parotid gland were noted more often in the SLE group (53%) than in the series as a whole (29%). Strictures in the duct and ductuli were also more common in the SLE group (67%) than in the whole series (50%). Sialectasis was only slightly more common (40%) in the SLE group than in the series as a whole (38%). Two contrast media, Amipaque (metrizamide, 170 mgI/ml) and Urographin 60% (sodium amidotrizoate + meglumin amidotrizoate 10:66, 290 mgI/ml) were used, of which Amipaque proved to be clearly better tolerated. This difference is probably due to the low osmolarity of Amipaque.

Adult

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

Sjögren's syndrome in systemic lupus erythematosus and rheumatoid arthritis: immune effector cells in salivary glands.

A simultaneously capturing azo dye method for acid alpha-naphthyl acetate esterase was used to characterize the cellular infiltrate in labial salivary glands in 25 patients with Sjögren's syndrome (SS). There was no significant difference in the T-pattern lymphocyte percentage in situ between the untreated group with SS and the group treated with 10 +/- 2 mg prednisone/day. There was a significant correlation (P less than 0.05) between the T-pattern lymphocyte percentage in situ and the focus-score value. In secondary (2 degrees) SS in cases of systemic lupus erythematosus (SLE) and rheumatoid arthritis, respectively, 55% +/- 4% (range 41-69) and 43% +/- 7% (range 15-80) of all inflammatory cells in the periductal lymphocyte-rich infiltrates were T-pattern lymphocytes. In other SS patients the corresponding value was 28% +/- 7% (range 4-50). The T-pattern lymphocyte percentage in situ was dependent on the disorder associated with SS (P = 0.07). The present results indicate the dominance of T-lymphocytes in situ in 2 degrees SS with SLE and suggest that there are differences in cell-mediated immunity in different clinical subgroups of SS.

Adult

Immunocompetent cells in labial salivary glands in secondary Sjögren's syndrome associated with SLE.

T and B lymphocyte (sub)populations were identified by monoclonal hybridoma antibodies (the avidin-biotin-peroxidase complex method), in the periductal lymphocyte-rich infiltrates in the labial salivary glands of 8 patients with secondary Sjögren's syndrome (2 degrees SS) associated with systemic lupus erythematosus (SLE). 59 +/- 7% and 17 +/- 3% of inflammatory round cells in situ were T3-positive and surface(SIg)- or cytoplasmic(CIg) immunoglobulin-positive, respectively. This suggests a local T lymphocyte dominance in salivary glands in 2 degrees SS associated with SLE. The local ratio of cells expressing T inducer/helper: T suppressor/cytotoxic phenotype was 3.5 +/- 0.8 (range 0.9-7.6) indicating large variations between individual patients. 46 +/- 9% of all inflammatory cells in situ were endogenous peroxidase-negative, Ia-positive cells, suggesting an active role for the locally accumulated T lymphocytes.

Adult