Separation of rheumatoid factors of different specificities using columns conjugated with gamma‐globulin

Williams, Ralph C.; Kunkel, Henry G.

doi:10.1002/art.1780060602

Cited by 66 publications

(18 citation statements)

References 22 publications

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“…This could be due to a common aetiology affecting multiple factors or to the occurrence of a single rheumatoid factor which reacts with both systems. Such a factor has beeni found in patients with RA by Heimer and Schwartz (1961) and Williams and Kunkel (1963), and the greater prevalence of RA in those in whom both tests were positive in the Wensleydale population sample and also in the Heinola survey reported by Aho and others (1961) supports the theory that RA is associated with a single factor reacting with both systems.…”

Section: Discussionsupporting

confidence: 65%

Rheumatoid Factors in a Rural Population

Valkenburg

Ball

Burch

et al. 1966

Annals of the Rheumatic Diseases

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Section: Discussionsupporting

confidence: 65%

Rheumatoid Factors in a Rural Population

Valkenburg

Ball

Burch

et al. 1966

Annals of the Rheumatic Diseases

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“…Steric exposure of neoantigens may be implicated in some tumor-specific antigenic systems; the carcinoembryonic antigen appears to possess an antigenic site that is exposed only at low ionic strength (16). Cleavage fragments of IgG possess a unique determinant(s), which is elicted by enzymes of differing specificities (4,17 ments expressing fg-Dneo must be greatly reduced. A differential cleavage of fibrinogen by these proteases and by plasmin is consistent with this explanation (Fig.…”

Section: Discussionmentioning

confidence: 99%

Molecular Events Responsible for Modulation of Neoantigenic Expression: The Cleavage-Associated Neoantigen of Fibrinogen

Plow

Edgington

1972

Proc. Natl. Acad. Sci. U.S.A.

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Molecular events responsible for modulation of neoantigenic expressions of a defined molecule have been explored in relation to three hypothetical molecular models (see below). Fibrinogen and its cleavage-associated neoantigen have been used as a prototype system. Physicochemical and enzymatic factors influencing neoantigenic expression were evaluated. The cleavage-associated neoantigen was not only exposed by plasmin and enzymes of similar specificity, but also in a qualitatively and quantitatively deficient fashion by enzymes of differing specificities. Denaturation of fibrinogen via reduction or pH alteration did not induce the neoantigen, but oxidation of the native fibrinogen molecule did elicit this neoantigenic expression. The neoantigen, once exposed on the D-fragment, was relatively stable to physical and chemical denaturation. These results are inconsistent with proposed cleavage site specific and neoconformational determinant models and are consistent with a steric model, which postulates that the cleavage-associated neoantigenic determinant is buried in native fibrinogen but is exposed in certain altered molecular species. The importance of molecular conformation in the exposure of antigenic expressions of a molecule and in modulation of the binding affinity of a neoantigen for specific antibody is demonstrated.The antigenic expressions of a protein molecule appear to be determined at all levels of molecular organization (1, 2). Although antigenic determinants may be dependent upon genetically-coded amino-acid sequences, tertiary conformation and quaternary organization, which can be modified at a more peripheral level of biological organization, may be equally effective in determination or modulation of antigenic expression. The deletion of select native antigens and the appearance of neoantigenic determinants on altered molecules occurs with aggregation of bovine serum albumin (3) and after enzymatic cleavage of immunoglobulin G (IgG) (4) or bovine serum albumin (5) by pepsin. The cleavage of fibrinogen by plasmin, a physiological mechanism (6), generates two terminal cleavage fragments that are pathobiologically significant, fg-D and fg-E, and are noncovalently associated with one another (7, 8). We have recently reported the emergence of a neoantigenic expression(s) after plasmin cleavage of fibrinogen (9). This cleavage-associated neoantigen (fg-Dn..) was localized in the fg-D fragment and has now been demonstrated after in vivo, as well as in in vitro, cleavage of fibrinogen (10).This system provides a model in which the emergence and modification of neoantigenic expressions can be studied. Similar considerations may apply to neoantigens associated with neoplasia and some immunologically mediated diseases arising from modification of molecular species on the surfaces of normal cells. In consideration of the emergence of a neoantigenic expression via enzymatic molecular cleavage, three hypothetical schematic models are considered here (Fig. 1). All have conformational elements, but also ...

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“…The difference in the capacity of the yM and yG anti-yglobulins from the same patient to agglutinate sensitized red cells suggests that the specificities are not identical. Since the yM anti-y-globulins in individual sera can be heterogeneous with respect to reactivity in various test systems (30), it is possible that some molecules of corresponding specificity exist. The possibility also exists that this may reflect differences in avidity or agglutinating efficiency.…”

Section: Ments Showing the Distribution Of Anti-y-globulin Activity Imentioning

confidence: 99%

Characterization of the gamma-globulin complexes present in certain sera having high titers of anti-gamma-globulin activity.

Schrohenloher¹

1966

J. Clin. Invest.

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Separation of rheumatoid factors of different specificities using columns conjugated with gamma‐globulin

Cited by 66 publications

References 22 publications

Rheumatoid Factors in a Rural Population

Rheumatoid Factors in a Rural Population

Molecular Events Responsible for Modulation of Neoantigenic Expression: The Cleavage-Associated Neoantigen of Fibrinogen

Characterization of the gamma-globulin complexes present in certain sera having high titers of anti-gamma-globulin activity.

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