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PubMed1982

The complement fixing properties and class distribution of rheumatoid factors (antiglobulins) in rheumatoid arthritis and other diseases.

The MRSPAH (mixed reverse solid-phase passive antiglobulin haemadherence) test for antiglobulins (Agbs) of IgA, IgG and IgM classes has been quantified and also modified to measure their C3 fixing activity. An alternative ELISA technique is also described. Levels of all Agbs and their C3 fixing activity were significantly raised in established rheumatoid arthritis (RA) patients, early RA patients and established SLE patients. Ankylosing spondylitis (AS) patients had normal levels of Agbs and C3 fixation. Patients with infectious mononucleosis (IM) had high levels of all Agbs, but these did not fix complement. Thus, C3 fixing activity of Agbs is heterogeneous and raised levels are associated with the presence of joint disease. Isolated IgA, IgG and IgM fractions showed examples of Agbs which fixed C3. The proportion of C3 fixed per unit weight of Agbs was no greater in 'hidden' Agbs from serum and synovial fluids (SFs) than in untreated serum, and Agbs in SF do not fix more C3 than in serum. We conclude that the C3 fixing activity of Agbs is not directly related to affinity.

Antibodies, Anti-Idiotypic↗
PubMed1993

Synovial IgG rheumatoid factors show evidence of an antigen-driven immune response and a shift in the V gene repertoire compared to IgM rheumatoid factors.

We have established IgG rheumatoid factor (RF)-secreting hybridoma cell lines from the synovial tissues of three patients from whom we have previously characterized several IgM RF. The IgG RF bind human and rabbit IgG and form intracellular complement-fixing complexes indicative of a self association process in vivo. Nucleotide sequence analysis revealed that two IgG RF used VHIII gene segments, while one used a VHI gene segment. The VL gene usage consisted of a V kappa 1, a V lambda 2 and a V kappa 4/V kappa 6 hybrid, confirming our previous findings that many different VL genes can contribute to RF specificity. Although the IgG RF used VH genes from the same families that dominated the IgM RF response, two of the actual gene segments employed were not found among the IgM RF. In contrast to IgM RF, which in general were not very mutated, the IgG RF showed somatic mutations characteristic of an antigen-driven immune response.

Amino Acid Sequence↗
PubMed1988

Associations of HLA-DR4 with rheumatoid factor and radiographic severity in rheumatoid arthritis.

Possible associations between HLA-DR4 and laboratory, radiographic, joint count, functional, and demographic measures of clinical status were analyzed in 154 white patients with rheumatoid arthritis. Overall, 65 percent of the patients were HLA-DR4 positive, similar to other series. HLA-DR4 was associated significantly with the presence of rheumatoid factor and more severe radiographic changes. HLA-DR4 was not associated with significant differences in demographic, joint count, or functional measures of clinical status. HLA-DR1 was not associated significantly with differences in the presence of rheumatoid factor, radiographic changes, or other measures of clinical status. Selective associations of HLA-DR4 with rheumatoid factor and radiographic scores were more marked in men than in women. Patients who were putatively homozygous for HLA-DR4 were all seropositive and had more severe radiographic changes than patients who were heterozygous for HLA-DR4.

Activities of Daily Living↗
PubMed1992

IgM rheumatoid factors in patients with rheumatoid arthritis derive from a diverse array of germline immunoglobulin genes and display little evidence of somatic variation.

Rheumatoid factors (RF) are present in the plasma of patients with rheumatoid arthritis (RA) although the site of synthesis of most of these antibodies is within the synovium. This report primary concerns RF of the IgM isotype. While a few of the RF derive from patients with systemic lupus erythematosus or from normal individuals, the remaining derive from the inflamed synovial tissue of patients with RA. Two RF are encoded by members of the VH1 gene family, 8 from the VH3 family and 2 from the VH4 family. Two polyreactive antibodies derive from the VH3 family and 2 come from the VH4 family. This distribution is not fundamentally different from the distributions seen in a large array of autoantibodies and antibodies to external antigens. Similarly, the light chains derive from most of the known kappa and lambda VL families. It is hard to escape the preliminary conclusion that gene segments from virtually any light chain variable region can contribute to RF or polyreactive antibody structures. Most IgM RF and polyreactive antibodies are direct copies of germline genes in one of their polypeptide chains or at most are 2 nucleotides away in one of their chains from a known germline gene.

Antibody Formation↗
PubMed1987

IgM, IgG and IgA rheumatoid factors (antiglobulins) in early rheumatoid arthritis and their production of articular index over one year.

An enzyme-linked immunosorbent assay was used to detect antiglobulins (rheumatoid factors, RF) of various classes in 33 patients with recently diagnosed rheumatoid arthritis and to follow their progress with 3-monthly checks for 1 year. For RF, IgA-RF and IgM-RF showed greater sensitivity than the latex test, either or both being positive in 76%. There was no correlation between any of the measures of RF and patient's clinical status as judged by articular index (AI), or serum CRP level. For individual patients, RF levels varied considerably between assessments. The best predictors of clinical status over 1 year were the initial AI and the latex test for RF. While class-specific measurement of RF is more sensitive than the latex test, the variation of individual classes of antiglobulins over time within individual patients makes them less helpful as predictors of disease progress.

Arthritis, Rheumatoid↗
PubMed1993

Rheumatoid factors from patients with rheumatoid arthritis react with Des-Lys58-beta 2m, modified beta 2-microglobulin.

Ten polyclonal IgM rheumatoid factor (RF) preparations, affinity-purified from IgG columns, from patients with rheumatoid arthritis were studied for their ELISA reactivity with native beta 2m in parallel with Lys58-cleaved beta 2m and Des-Lys58-beta 2m, the latter representing cleavage products of the native molecule present in some pathologic human sera. Most RF showed positive reactions with the native form of beta 2m but reduced reactivity for the cleaved forms of beta 2m. Reactions between cleaved beta 2m and RF, in solution, were demonstrated by inhibition of RF binding to native beta 2m by preincubation with a range of concentrations of Des-Lys58-beta 2m. By contrast, eight of nine murine MoAbs to human beta 2m showed approximately equivalent binding to native beta 2m, Lys58-cleaved beta 2m, and Des-Lys58-beta 2m. Reactions between individual human RF and the altered forms of beta 2m (Lys58-cleaved beta 2m and Des-Lys58-beta 2m) appeared to parallel the previously determined beta 2m single amino acid specificities, in that RF showing strong reactivity with Lysine 58 also showed a significant diminished reactivity with the Des-Lys58-beta 2m lacking the critical lysine residue. The present studies demonstrate that while human RF react with Lys58-cleaved beta 2m or Des-Lys58-beta 2m, preferential reactivity is observed for native unaltered beta 2m.

Amino Acid Sequence↗
PubMed1985

IgM, IgA and IgG rheumatoid factors in patients with rheumatoid arthritis and normal donors.

IgM, IgA, and IgG Rheumatoid Factors (RF) were measured by ELISA assay in serum from 26 patients with definite rheumatoid arthritis (RA) and 11 normal controls. IgM-RF was assayed by ELISA, radioimmunoassay, and also by the standard latex fixation test in all sera from RA patients. In patients with RA quantitative amounts of IgM, IgA, and IgG-RF as estimated by ELISA were highly correlated. Significant correlations were found between a physician's rating of disease activity and IgG-RF (r = 0.44; p less than .02) and IgA-RF (r = 0.38; p = .06 but not for IgM-RF as measured in any of the three assays.

Adult↗
PubMed1987

Analysis of combined rheumatoid factor determinations by the rheumatoid arthritis latex and sheep cell agglutination tests and the American Rheumatism Association criteria for rheumatoid arthritis.

The clinical records of randomly selected patients receiving both the sheep cell agglutination test (SCAT) and the latex agglutination test (RA latex) for rheumatoid factor (RF) were analyzed for the presence of American Rheumatism Association (ARA) criteria for rheumatoid arthritis (RA). When both tests were positive there was a 3-fold increase compared to only one test positive in the relative risk that a patient met ARA criteria for RA, and there was a 2-fold increase in the probability that a patient with 2 positive tests had classical RA compared to only a positive RA latex. The occurrence of RF reactive with both human and rabbit IgG identifies a population of patients likely to have more ARA criteria for RA and classical disease.

Agglutination Tests↗
PubMed1986

The distribution of class-specific rheumatoid factors is similar in rheumatoid and pre-illness sera.

The occurrence of IgM, IgG, and IgA class rheumatoid factors (RF) was compared by means of ELISA in 21 sera from patients with established rheumatoid arthritis (RA) and in 22 pre-illness sera from subjects who 4 months to 5 years later developed seropositive rheumatoid arthritis. The positive cases were virtually confined to three groups of about equal size: positive for all three RF classes, positive for IgM-RF and IgG-RF, and positive for IgM-RF only. Thus, the distribution of the RF isotypes was similar in rheumatoid and pre-rheumatoid sera.

Arthritis, Rheumatoid↗
PubMedDate not supplied

The photometric latex test for rheumatoid factors in patients with rheumatoid arthritis. I. correlation with other serologic tests.

The photometric latex test (PLT) for the detection of rheumatoid factors (RF) has been correlated with the sensitized sheep cell test (SSC) and the latex slide test (LST). A total of 377 sera from patients with rheumatoid arthritis (RA) and 120 sera from control subjects were examined. When the PLT was carried out on the native sera at a lower buffer ionic strength (0.05 M), agglutination was noted in over 99% of cases, indicating interaction of complement with human immunoglobulin bound to the latex particle surface. Although thermal inactivation eliminated most of the complement agglutination, an increase in ionic strength (0.5 M) was found to be essential for measuring only RF agglutination. The serologic data were analysed statistically by computer. A highly significant correlation was found between all serologic tests and RA sera, but there was no such correlation with the control sera. The specificity of all tests was generally over 90% and did not vary significantly, but the sensitivity varied from 52.0% to 71.1%, confirming that about one-third of all RA patients are seronegative. The tests were analysed for their total diagnostic capability. The PLT with native sera at higher ionic strenght proved to be the most sensitive, but with thermally inactivated sera it had a better diagnostic capacity. The SSC test appeared to be less sensitive and of lower diagnostic validity. Rapid LST tests were clearly inferior to PLT tests. The PLT can be used as a reliable and straightforward serologic method of diagnosis in RA, especially when carried out at a higher ionic strength and with thermally inactivated sera. It should be given preference over other serologic tests for RF and could well become standard practice in rheumatologic serology as a substitute for the SSC test.

Arthritis, Rheumatoid↗
PubMed1961

Specificity of the reaction between rheumatoid factors and gamma globulin.

Rheumatoid factors in the sera of patients with rheumatoid arthritis appear to be specifically directed against genetically determined "antigens" in human gamma-globulin. At least eight rheumatoid factors of differing specificity exist; usually several are present in combination in the same serum. The different rheumatoid factors can be readily detected through their pattern of reactivity with anti-Rh antibodies from different individuals. Rheumatoid factors in diseases other than rheumatoid arthritis were found to have a more restricted specificity, contrasted to the broader reactivity of the factors in most rheumatoid arthritis sera. A specificity similar to that for incomplete antibodies was not demonstrated for the reaction of rheumatoid factors with aggregated gamma-globulin or with gamma-globulin to form the "22S complex." In certain instances, using the anti-Rh system, rheumatoid factors were found to react poorly with the patient's own gamma-globulin, compared to that of other individuals of different genetic gamma-globulin types. These results, as well as additional indirect evidence, indicate that the rheumatoid factors can possess isospecificity. However, a certain degree of autospecificity was also found which was most clearly evident through complex formation with the patients own gamma-globulin and in the reaction with aggregates. The relevance of these findings to possible isoantibody as well as autoantibody concepts is discussed.

Antibodies, Anti-Idiotypic↗
PubMed1985

Hidden and classical 19S IgM rheumatoid factor in a juvenile rheumatoid arthritis patient.

Hidden 19S IgM rheumatoid factors (RF), i.e., 19S IgM RF which can be detected in the IgM containing fraction after acid gel filtration of serum, are found in 59-68% of patients with juvenile rheumatoid arthritis (JRA). Their presence generally correlates with disease activity. We describe a 12 year-old female with a polyarticular onset of JRA who, during her first 15 months of disease, was seronegative but had hidden RF titers of 1:128----1:256. Inhibition studies on her hidden RF showed specificity for HIgG greater than RIgG and equal specificity for the human IgG subclasses (IgG1 = IgG3). In the second and third year of disease, she became seropositive with RF titers varying from 1:40 to 1:320 while her hemolytic titers on her IgM fractions were decreased from 1:128 to 1:32. Inhibition studies now demonstrated a higher avidity for RIgG; and HIgG3 inhibited more than HIgG1. These studies documented for the first time a JRA patient who early in the disease was negative for RF and positive for hidden RF, and who later became seropositive.

Arthritis, Juvenile↗