Irwin Oreskes

Changes in rheumatoid factor activity during the course of sarcoidosis

Abstract Among sixty-four patients with a tissue-confirmed diagnosis of sarcoidosis studied for the presence of rheumatoid factor in their serum an over-all frequency of 38 per cent was found on initial testing. The presence of rheumatoid factor was unrelated to the presence or absence of joint symptoms. Rheumatoid factor was more prevalent in active disease processes than in inactive disease, and in patients with later stages of pulmonary involvement than with hilar node enlargement alone. Patients who exhibited rheumatoid factor were ill with sarcoidosis approximately twice as long on the average as those who did not. Rheumatoid factor was found nearly twice as often in female subjects as in male subjects. The presence of rheumatoid factor initially was of little prognostic significance, but disappearance or reduction of rheumatoid factor titers upon later retesting was associated with an improving clinical course. Conversely, appearance of rheumatoid factor for the first time or increase in titer on retesting was associated with continued disease activity and with a relatively poorer clinical outcome. The tanned sheep cell test was considerably more sensitive than latex tests in detecting rheumatoid factor activity in sarcoidosis.

Size fractionation of thermal aggregates of immunoglobulin G

Purified pooled human immunoglobulin G (IgG) in solution, when extensively heated at high temperatures or for long periods, irreversibly aggregates and insoluble precipitates result. However, when IgG solutions are heated in the temperature range 55-65 degrees C for more limited time periods, soluble turbid polydispersed aggregate mixtures are obtained. Gel filtration of such aggregate mixtures on calibrated Bio-Rad A-150m columns demonstrates a continuous size distribution from dimers to aggregates as large as 4 X 10(7) Da (200-mers) with no particular size predominant. Chromatographically reproducible cuts of narrow size heterogeneity can be obtained by short-time fraction collection. Elution-time reproducibility is excellent both for mixture and for individual cuts. Stability studies indicate that reproducible and stable aggregates may be made from purified IgG and that fractionated aggregates should be stored quick-frozen until needed. Sized IgG aggregates have proved useful in reactivity studies with rheumatoid factor, animal anti-IgG antibodies, and complement.

Mechanism of Particulate Carrier Reactions: V. ADSORPTION OF HUMAN GAMMA GLOBULIN TO 0·2 MICRON DIAMETER LATEX PARTICLES AND THEIR AGGLUTINATION BY RHEUMATOID FACTOR

Polystyrene latex particles of 0 81. diameter have been in use since 1956 for the detection of rheumatoid factors in the latex-fixation test of Singer and Plotz (1956). The use of this test or of its various modifications in rheumatoid diseases has been widespread, and this subject has been recently reviewed (Singer, 1961). In the original procedure for the detection of rheumatoid factors, the suspension of 0 8 ,u diameter latex particles was sensitized by the addition of an excess of human gamma globulin (whole Fraction II). Under the conditions of the test procedure, about 90 per cent. of the added gamma globulin was not adsorbed and consequently remained in solution (Singer, Altmann, Goldenberg, and Plotz, 1960). This excess gamma globulin in the test system often resulted in variable and uncontrolled inhibition effects, thus making the test difficult to standardize and not always reproducible. More recently, several modifications have been introduced (Singer, Plotz, and Eason, 1961; Singer, Oreskes, Hutterer, and Ernst, 1962) in the original latex-fixation procedure. A smaller latex particle of 0 2 ,u diameter had been substituted for the previously employed 0 8 ,t particle. In addition, the excess unadsorbed gamma globulin remaining in solution has been removed by high speed centrifugation and washing of the coated particles. The present report is concerned with the quantitative aspects of human gamma globulin (HGG) adsorption to the 0 2 pt diameter latex particle. In addition, data on quantitative agglutination of sensitized latex particles by rheumatoid factor (RF) preparations are also reported.

The mechanism of particulate carrier reactions: III. The stabilizing effect of serum proteins☆

Abstract 1.1. FII and FV alone or in mixtures are adsorbed onto the surface of latex particles or tanned sheep cells and produce agglutination with both rheumatoid factor and antialbumin systems. 2.2. Adding FV or FIV stabilizes latex particles and lowers rheumatoid factor titers by their protective colloidal action. FIV is more effective than FV in this respect. 3.3. Added FIV produces a prozone effect with the FII latex particle system but not with the FII sheep cell system. 4.4. The probable mechanism of the protective action of serum protein fractions on particulate carrier systems is discussed.

Rheumatoid factor activity in heroin addicts on methadone maintenance.

It is now well known that rheumatoid factors (RF) or antigamma globulin antibodies are found in many individuals with a wide variety of diseases other than rheumatoid arthritis (Bartfeld, 1960, 1969; Oreskes and Spiera, 1966, 1967). In many of these diseases the presence of RF seems to be related to a previous or concurrent history of chronic antigenic stimulation. Examples of this include cases of subacute bacterial endocarditis (Williams and Kunkel, 1962) and tuberculosis (Singer, Plotz, Peralta, and Lyons, 1962), as well as diabetics on long-term insulin therapy (Oreskes and Spiera, 1973). Similarly, RF is present in patients who have received multiple transfusions (Vierucci, 1965) or vaccinations (Aho, Konttinen, Rajasalmi, and Wager, 1962). Tuffanelli (1968), Nickerson, Williams, Boxmeyer, and Quie (1970), and Ryan, Parker, and Williams (1972) have reported significant levels of RF activity in heroin addicts. Typically, individuals who are addicted to heroin repeatedly inject themselves with heroin which may also contain other foreign substances. It is a plausible view that heroin or its adulterants are antigenic, or may become antigenic by forming complexes with endogenous protein. Therefore, one might expect in many of these individuals production of antibodies to these antigens. Resultant antigen-antibody complexes could in turn serve as the stimulus for RF production. An alternative possibility is that RF in heroin addicts is in some way related to the liver dysfunction commonly seen in such individuals. Correlation of RF activity and liver disease has been frequently reported (Bartfeld, 1969). The purpose of the present study was to follow the course ofRF in heroin-dependent persons on methadone maintenance to obtain additional information regarding the pathogenic mechanism of RF production.

INFLUENCE OF PH, IONIC STRENGTH AND HUMAN GAMMA GLOBULIN CONCENTRATION ON STABILITY OF POLYSTYRENE LATEX PARTICLE SUSPENSIONS.

Summary Polystyrene latex particle suspensions exhibit the properties of lyophobic colloids. Addition of small amounts of human gamma globulin serves to destabilize the LP whereas larger amounts exert a stabilizing protective action. The protective action of HGG is strongly pH dependent and is least at the protein isoelectric point. Use of uncoated latex particles for detection of rheumatoid factors may be complicated by the fact that such particles spontaneously precipitate in very dilute protein solutions.

Electrical Conductance Changes Associated with Interaction of Viral Antigen and Its Specific Antiserum.

Summary Measurements of electrical conductance have been performed on varied mixtures of Echo 19 virus and its specific rabbit antiserum. A 6.9% decrease in conductance (increase in resistance) was observed in the vicinity of the antibody neutralization point as measured by viral growth inhibition, No such decrease in conductance was observed with mixtures of antiserum and ultraviolet irradiated inactive antigen.