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Diagnostic and prognostic characteristics of the enzyme linked immunosorbent rheumatoid factor assays in rheumatoid arthritis.

OBJECTIVE: To determine the diagnostic and prognostic test qualities of the enzyme linked immunosorbent assays (ELISA) for rheumatoid factor isotypes in rheumatoid arthritis (RA), and to compare them with the latex fixation test. METHODS: Rheumatoid factor tests were performed in 1988 consecutive new rheumatology outpatients within two months after their first visit to the outpatient clinic of the Department of Rheumatology of Leiden University hospital. The sensitivity, specificity, accuracy, and predictive values of the tests in discriminating RA from non-rheumatoid arthritis and erosive from non-erosive disease after two years of follow up were determined and presented as receiver operating characteristic curves and post-test probability curves. RESULTS: The sensitivity of the ELISA for IgG, IgA, and IgM rheumatoid factor for RA versus all controls at optimal cut off titres was 72%, 44%, and 69%, respectively; the specificity was 52%, 84%, and 86%. For the latex fixation test the sensitivity was 66% and the specificity 91%. The post-test probability of RA, at a clinical prevalence rate of 12%, given a positive test result in the ELISAs for IgG, IgA, and IgM rheumatoid factor and the latex fixation test, was 17%, 27%, 40%, and 49%, respectively; with negative test results the probability was 7%, 8%, 5%, and 5%, respectively. The specificity of all tests in discriminating erosive from non-erosive RA at two years was low: 41%, 44%, 47%, and 58% for the ELISAs for IgG, IgA, and IgM rheumatoid factor and the latex fixation test, respectively. CONCLUSION: The ELISAs for IgG and IgA rheumatoid factor are of no significance in diagnosing RA and in the prediction of erosive disease. The ELISA for IgM rheumatoid factor is a reasonable alternative for the latex fixation test when age and gender are taken in to consideration. The specificity of all rheumatoid factor tests in discriminating erosive from non-erosive RA is low.

Adolescent↗

Usefulness and limitations of three serologic methods for diagnosing or excluding chlamydiosis in birds.

Diagnostic serology by use of elementary body agglutination is the most useful serologic method for diagnosis of chlamydiosis in birds, because it detects only IgM activity. A titer of 10 in budgerigars, cockatiels, and lovebirds and of > or = 20 in other types of birds is interpreted as being indicative of current infection. Latex agglutination, with detects IgM and IgG activity, may be useful in detecting large changes in titer. Direct complement fixation, detecting only IgG activity, is usable to detect past infection whenever elementary body agglutination and latex agglutination titers are < 10. Limitations of serologic results necessitating additional confirmatory testing are lack of titers in the acute phase of disease and diagnostic titers in clinically normal birds with low-grade chronic infections and in birds with prolonged maintenance of titers. Additional suggested examinations are chlamydial culture by use of choanal/oropharyngeal swab samples, WBC count, determination of hepatic-associated enzyme activity, chlamydial ELISA by use of the aforementioned swab samples, and additional serologic testing.

Agglutination Tests↗

Circulating IgM rheumatoid factors in patients with primary Sjögren's syndrome.

The importance of circulating rheumatoid factors (RF) in primary Sjögren's syndrome (primary SS) was evaluated retrospectively by examining medical case records of 80 consecutive patients. Increased levels of IgM RF, determined by the Waaler test, the latex fixation test and/or the ELISA test, were found in 47 patients (59%). Follow-up examination of the 41 patients in whom more than one (mean 4.9 (2-12)) RF determination over at least a two-year period (mean 5.6 (2-13) was present, showed that 12/41 patients (29%) were permanently RF-negative, 7/41 (17%) exhibited both positive and negative RF values and 22/41 (54%) were permanently RF positive. Variations in IgM RF levels were unrelated to disease duration. Except for involvement of joints, extraglandular manifestations were more common in patients with increased levels of RF. This finding, however, was only significant within the group of more rarely occurring extraglandular manifestations (serositis, interstitial nephritis, cutaneous vasculitis, lymphoproliferative disorders and intermittent fever) (p less than 0.01). IgM RF levels were likewise positively correlated (p less than 0.001) to positivity of IgG antinuclear antibodies as well as to the plasma concentrations of immunoglobulins.

Adult↗

Subclinical intra-amniotic infection in asymptomatic patients with refractory preterm labor.

The purpose of this prospective investigation was to determine the incidence of subclinical intra-amniotic infection in asymptomatic patients who had intact membranes and refractory preterm labor. Refractory preterm labor was defined as persistent uterine contractions despite maximum recommended doses of parenteral tocolytics, or recurrent preterm labor within three days of successful transition to oral tocolytics. Amniotic fluid was cultured aerobically and anaerobically and prepared for Gram stain and group B streptococci latex fixation test. One of 24 women had a positive latex fixation test, but the culture was negative. One culture was positive for isolated colonies of Corynebacterium sp. None of the patients developed clinical evidence of intra-amniotic infection or postpartum endometritis. The mean prolongation of pregnancy was 31 days (range 1-63). None of the infants had evidence of sepsis in the immediate neonatal period. In this population, subclinical infection was an uncommon cause of refractory preterm labor.

Amniocentesis↗

A new assay for rheumatoid factor.

This solid-phase immunoassay for detection of rheumatoid factor involves a specially prepared indium surface that renders protein layers visible and therefore does not require tagged protein. Using appropriate discriminatory values, we found agreement with results of a standard latex-fixation test in controls and patients with rheumatoid arthritis. About half of the patients with rheumatoid arthritis that were seronegative by this latex fixation test had positive tests by the present assay. Rheumatoid factor of both the IgM and IgA class may be easily assessed.

Arthritis, Rheumatoid↗

Evaluation of diagnostic procedures for detection of mycoplasmal pneumonia of swine.

The complement-fixation test (CFT), a latex-agglutination test (LAT), and Mycoplasma hyopneumoniae isolation procedures were compared with gross and microscopic lung evaluations for the routine diagnosis of mycoplasmal pneumonia (MP) of swine. The difficulty and variability of M hyopneumoniae isolation rendered this technique unacceptable. In market-weight swine, the finding of typical gross lesions was correlated with CFT results (P less than 0.005). The MP status of a herd could not be determined by use of these techniques in 4- to 9-week-old pigs. No technique could be used alone to establish a diagnosis. Gross and microscopic examination of all slaughter specimens, CFT, and clinical evaluation of the herd, used in combination, were the most useful means of determining the MP status of the herd.

Animals↗

A COMPARISON OF THE ROSE-WAALER, LATEX FIXATION, "RA-TEST," AND BENTONITE FLOCCULATION TESTS.

The bentonite flocculation test of Bozicevich, Bunim, Freund, and Ward (1958), the latex fixation test of Singer and Plotz (1956), and the "RA-test" (a latex reagent for use as a slide test) of Hyland Laboratories have been compared with each other and with a modified Rose-Waaler test, the behaviour of which has been previously extensively investigated. In these tests sera from 2,250 patients were tested by two or more methods on 3,000 occasions. The findings of this trial are set out and the merits of the tests and reasons for disagreement among them are discussed. It is concluded that the most satisfactory means of testing rheumatoid sera is by the Rose-Waaler test and the "RA-test," or a satisfactory modification of it, in parallel.

Journal Article↗

Measuring rheumatoid factor in nonrheumatoid subjects: immunoturbidimetric assay, latex slide test, and enzyme-linked immunosorbent assay compared.

Previous studies of patients with rheumatoid arthritis (RA) have shown a good correlation between results from immunoturbidimetric assays of rheumatoid factor (RF) and latex fixation tests. To extend the research to non-RA subjects, we tested sera from 1000 pregnant women, half each in the first and third trimesters. By turbidimetry, 24 non-RA sera were regarded as positive for RF (greater than or equal to 20 int. units/mL) and 18 sera as borderline (15-19 int. units/mL). By the latex fixation test, 28 non-RA sera gave a clear reaction (positive) and 17 sera a weak reaction (borderline). The association between the tests was statistically highly significant (P less than 0.001). All sera with positive and borderline reactions were tested by enzyme-linked immunosorbent assay for RF isotypes, together with a random subsample of about one-sixth of the original serum samples. Positive RF results by immunoturbidimetry were predominantly due to the presence of IgM-RF. In contrast to some earlier findings, we saw no difference in the prevalence of positive RF reactions between sera from the first and third trimesters.

Enzyme-Linked Immunosorbent Assay↗

[Does seronegative chronic polyarthritis have a special place? Clinical, biochemical and immunogenetic profile of early seronegative seropositive chronic polyarthritis].

In the framework of an early-diagnosis out-patients clinic 100 patients (mean age 51 years), 82 of them female, were identified as highly suspicious of having chronic rheumatoid arthritis of recent onset (2-12 months). Five or more ARA criteria were present in 77 patients. IgM rheumatic factor was present in serum of 51 patients (latex-fixation test). A Waaler-Rose test of greater than or equal to 32 IU/ml was present in 21. After adjusting for alpha errors, there was a significantly higher prevalence of HLA-DR4 among those seropositive in the latex fixation test (64 vs 29%). A further 19 constitutional, anamnestic, clinical, biochemical and psychosocial criteria failed to reveal any different distribution between seropositive and seronegative cases. Using the specific definition of seropositivity in the Waaler-Rose test eliminated HLA-DR4 differences. The latter did not serve as a distinguishing criterion. There was only a marginal difference between DR4-positive and negative patients. These results fail to lend support to recent views of a special position of seronegative chronic rheumatoid arthritis.

Arthritis, Rheumatoid↗

[Long-term observation of patients with isolated seropositivity for rheumatoid factor in the serum--clinical and immuno-rheumatological study].

A group of 40 subjects (33 women and 7 men) assembled in the course of several years comprised clinical and ambulatory patients. The main characteristic of the group was isolated seropositivity of rheumatoid factors assessed by the latex fixation test with titres of 1:320 and more in apparently healthy subjects. The mean age of the subjects at the beginning of the investigation was 39 years. They were followed up for 2-18 years, on average for 7.8 years. Regular clinical, biochemical and immunological check-up examinations were made after 1-2 year intervals. The latex fixation test was made in a test tube. The most serious manifestation was the development of rheumatoid arthritis in 7 subjects (6 women and 1 man). In two of them it was preceded by palindromic rheumatism. Two women have abortive manifestations of systemic lupus erythematosus. Seven developed, mostly repeatedly, tendovaginitis in the region of the flexors of the fingers and abductors of the thumb. Seven subjects suffered from polyarthritis of the hands. None of the subjects suffered from cirrhosis or monoclonal gammapathy. In the course of the investigation the titres of rheumatoid factors had a declining trend even to negative values. In 23 they became negative or had titres of 1:40. The high incidence of rheumatoid arthritis in 17% apparently healthy subjects with isolated seropositivity of rheumatoid factors emphasizes the importance of dispensarization of these subjects in a rheumatological surgery and of careful long-term follow up. Early administration of line 2 antirheumatic drugs could prevent a possible fatal course of rheumatoid arthritis.

Adult↗

Do clinical findings associate with radiographic osteoarthritis of the knee?

From a population survey of 2865 subjects, test characteristics of a number of clinical findings relating to knee osteoarthritis were calculated against the standard of radiographic diagnosis. The clinical findings included from the history were age, gender, current pain in the knee, swollen knee, pain in both hands, morning stiffness, osteoarthritis in any joint, pain or stiffness, or both, in knees or hips when rising from seated position, and pain in knees or hips while climbing stairs; and from the physical examination: Quetelet's index, Heberden's nodes, bony enlargement, palpable effusion, soft tissue swelling, limitation of knee function, pain with knee flexion, bony tenderness and, finally, the latex fixation test. Of 18 clinical variables, all but Heberden's nodes, palpable knee effusion, pain in both hands, and latex fixation test showed a significant association after adjustment for age. Neither one single variable nor a combination could predict radiographic osteoarthritis of the knee with reasonable accuracy and thus be applicable in clinical practice. The x ray film, therefore, keeps its place in the diagnosis of knee osteoarthritis in general practice as well as in epidemiological research.

Female↗

Some aspects of immunodiagnosis in amebiasis.

Antigen from axenically and with crithidia monoxenically grown amebae are compared in complement fixation test and indirect hemagglutination test. While similar reactivity was observed in indirect hemagglutination monoxenic antigen yielded extremely higher titers in complement fixation tests. Transient latex agglutinations of severely ill malaria tropica patients proved to be spontaneous in nature. It is recommended that extra latex is added to the test kits to provide for a check of positive sera for spontaneous agglutination. Glutaraldehyde treated and sensitized sheep red cells were stored under different conditions and their reactivity assessed over various periods of time. No loss of reactivity was found to occur under either condition after the respective times of observation, the longest of which lasted 12 months.

Amebiasis↗

Rheumatoid arthritis in Kenya. II. Serological observations.

Sera from 48 Kenyan Africans with rheumatoid arthritis, 43 patients with other diseases, and 98 blood donors were tested for the presence of rheumatoid factor by latex fixation tests using human European, human African, and rabbit immunoglobulin, and a sheep cell haemagglutination test. In the patients with rheumatoid arthritis the frequency of rheumatoid factor was comparable to that reported in series from Europe and the USA, thus differing from the findings in West Africa. In the control patients and blood donors a high frequency of positive tests for rheumatoid factor was found; a similar result has been obtained from population studies in other African countries. Broadly similar results were obtained with each of the latex tests, and these were found to be less specific for rheumatoid arthritis than the sheep cell haemagglutination test.

Adolescent↗

Standardisation of serological tests for rheumatoid factor measurement.

Standardisation of quantitative data obtained by several types of rheumatoid factor test was achieved by the use of a reference serum preparation. Interlaboratory comparability improved for the latex fixation test, the Waaler-Rose test, the IgM RF test by an enzyme linked immunosorbent assay (ELISA), and for the antiperinuclear factor test. Use of a common method and latex preparation was not sufficient to improve comparability for the latex test. The comparability of IgM RF tests by immunofluorescence (IF) was not changed by reading against a common reference. It is concluded that expression in international units, as defined by the World Health Organisation (WHO), improves interlaboratory comparison of quantitative data in rheumatoid serology.

Analysis of Variance↗