Studies on the Isolation and Characterization of the “Rheumatoid Factor”

Abstract

Considerable evidence has been accumulated which indicates that a large proportion of the sera from patients with rheumatoid arthritis contains a factor which has the property of agglutinating particulate bodies such as red blood cells or latex particles when they are coated with -y-globulin or antibodies. Some of these reactions have been employed as diagnostic procedures and the factor or group of factors involved has been termed the "rheumatoid factor." A number of observations (1, 2) have demonstrated that the rheumatoid factor is a y-globulin with the solubility properties of a euglobulin. More recently, ultracentrifuge experiments (3, 4) have indicated that the rheumatoid factor is a high molecular weight -y-globulin that exists in serum and plasma in the form of a complex. This complex can be visualized directly by means of the analytical ultracentrifuge in whole serum and in -y-globulin and euglobulin fractions and has a corrected sedimentation rate (s rate) of approximately 22S. Previous studies (4, 5) on the dissociation of the 22S complex by means of acid and urea have demonstrated that it is composed of two major constituents, one a 7S component and'the other 19S. The latter was found to be highly active by the serological reactions for rheumatoid factor. The rheumatoid factor thus appeared to belong to the 19S class of y-globulins which is known to include certain antibodies as well as the Waldenstrom type macroglobulins (6, 7).Considerable purification of the rheumatoid factor has been achieved by cellulose ion exchange chromatography (8,9), by elution from pneumococcus-antipneumococcus complexes (10), by elution from sensitized sheep cells (11), by ultrafiltration with membranes of graded porosity (12), and by preparative ultracentrifugation (4, 13), but isolation in sufficient amounts to determine the complete physical and chemical properties of the rheumatoid factor has not been reported. The observations that rheumatoid factor precipitated directly with y-globulin (14) which had been aggregated by the procedures of isolation or heating at 630C. for 10 minutes (3, 13) offered a method of ready concentration from large volumes of serum. Furthermore the direct visualization of rheumatoid factor in the ultracentrifuge offered a means of observing purification particularly from certain unique sera where it represented a substantial portion of the total y-globulin.In the present study rheumatoid factor has been obtained in a high state

Immunohistochemical studies of interleukin‐2 and γ‐interferon in rheumatoid arthritis

“…Affected patients show serum antibodies, generally referred to as rheumatoid factors, which react with Fc determinants on IgG (1)(2)(3). There is considerable evidence for the presence of a number of IgG-IgG and IgM-IgG complexes within serum and synovial fluid, and for activation of the complement system, particularly within prime areas of inflammation such as the rheumatoid synovium and adjacent synovial fluid (4-9).…”

Stabilizers and inhibitors in the sensitized sheep‐cell agglutination reaction

“…In sera from patients with rheumatoid arthritis, on the other hand, it seemed likely that these aggregates would react with rheumatoid factor to give a precipitate which is known to be insoluble in normal saline, but soluble in 4 to 6 M urea. 21 The remainder of the euglobulin which is soluble in saline and is then added to the test system would thus be free of aggregated gamma globulin and would either fail to inhibit or, if sufficient excess of rheumatoid factor were present, would even potentiate the test reaction.…”

“…21 The fractions were divided into a pellet which had been packed into a gel at the bottom of the tube and consisted primarily of aggregates and some 19 S gamma globulin, and two fractions which were distributed along the gradient. The top one contained primarily 7 S gamma globulin, while the middle fraction contained 7 S gamma globulin as well as most of the 19 S gamma globulin and most of the rheumatoid factor activity when such was present.…”

Rheumatoid factor and tumor-host interaction.

“…Rheumatoid factor (RF) is detected by routine laboratory techniques in serum from <4% of healthy adults under 65 years of age (1)(2)(3)(4)(5)(6)(7)(8). About 13-20% of unselected patients with malignancies are RF seropositive (1,4,5), and RF has been eluted from neoplastic but not from adjacent normal tissues (5).…”

“…In general, IgM is a more effective activator of complement than IgG (6, 7). However, the effect of IgM-RF on complement mediated reactions is variable (8)(9)(10)(11). For example, IgM-RF induces complement-mediated neutralization of herpes simplex virus complexed to IgG antibody (9).…”