Cryoimmunoglobulinemia in rheumatoid arthritis. Significance in serum of patients with rheumatoid vasculitis.

Abstract

A B S T R A C T Cryoglobulins were examined in a standardized manner in an unselected group of 35 patients with rheumatoid arthritis (RA) and 8 patients with RA complicated by cutaneous vasculitis and neuropathy. Optimum conditions for detection and characterization of cryoglobulins were established; the proportion of resolubilized to total precipitable protein remained constant in an individual patient under these conditions. All 8 vasculitis patients and 9 of 35 other patients with RA exhibited cryoglobulins; total protein and immunoglobulin content were significantly higher in the cryoglobulins of patients with vasculitis. Immunoglobulins G and M constituted two-thirds and three-quarters of the total protein in the cryoglobulins from uncomplicated rheumatoid and vasculitis patients, respectively. Serum antiglobulin titers were higher, and serum C3 levels were lower, in vasculitis patients compared to rheumatoid patients without vasculitis.Anti-gamma globulin activity was detected in all cryoglobulins from vasculitis patients. Cryoglobulin IgG and IgM were polyclonal. Density gradient analyses demonstrated the majority of the cryoglobulin antiglobulin activity to reside in the 19S IgM fraction. There was no evidence of a light weight (8S) IgM (2). Fourteen years after the original observation a patient was described who exhibited a similar phenomenon in the absence of malignancy and whose clinical features suggested an immunologically mediated disease (3). In recent years the emphasis of investigations concerning these proteins has changed. Now they are being viewed as circulating immune complexes because of the demonstration that they contain appropriate antigens, antibodies, or other immunoreactants that may relate to the pathogenesis of the disease they accompany (4). For example, cryoglobulins occur regularly in the sera of patients with diseases of known infectious etiology associated with "autoimmune" features, such as infectious mononucleosis (5, 6), leprosy (7), poststreptococcal glomerulonephritis (8), cytomegalovirus syndromes (6, 9), subacute bacterial endocarditis (10, 11), and tropical splenomegaly syndrome, resulting from chronic malarial exposure (12 METHODSPatients. Samples were obtained from 38 patients with RA, who were encountered in follow-up visits to a rheumatology clinic or hospitalized for either orthopedic or medical complications of their disease. They were chosen at random over a 6-mo period (January-June 1972). Patients with rheumatoid vasculitis were chosen consecutively as they were identified over a 12-mo period (January-December 1972). Patients with RA were representative of a total population of clinic-based rheumatoids; patients with vasculitis were either discovered in our clinic based population (W. H.), referred to our rheumatology division for evaluation of vasculitis (J. S., D. A., M. H., and L. T.), or hospitalized at the Veterans Administration Hospital for vasculitis (D. M., J. S., and R. M.). All patients (including those with vasculitis) met the American Rheumati...

Circulating and intra-articular immune complexes in patients with rheumatoid arthritis. Correlation of 125I-Clq binding activity with clinical and biological features of the disease.

“…Secondly, methods which are not specific for any particular antigen-antibody system were used. These studies were mostly qualitative and led to the demonstration of immune complex-like material such as cryoglobulins (16,17), macromolecular complexes (3,10,11), Clq precipitins (4,5), complement fixing material (4,16), or of complexes reacting with monoclonal rheumatoid factor (5). Recently, quantitative investigations were carried out using radioimmunological techniques such as for binding of complexes by rheumatoid factor (18,19) and macrophages (20).…”

Skin ulcers in a patient with Sjögren's syndrome

“…Mixed cryoglobulins are associated with chronic inflammation and infection, including hepatitis B and C viral infections, systemic lupus erythematosus, rheumatoid arthritis, and Sjö gren's syndrome (5)(6)(7)(8)(9)(10)12). Cryoglobulins may also be present in the sera of patients with chronic inflammatory conditions without clinical significance.…”

Cryoimmunoglobulinemia in felty's syndrome

“…All samples were collected and characterized using techniques previously described (7,8). In brief, 5 ml of sera were stored at 4°C for 72 hours; precipitates formed were washed three times with an excess of cold normal saline (0.15 M ) and solubilized in two steps-first in 0.5 ml of twice normal saline (0.3 M) at 37" for 1 hour, followed by the addition of 0.5 rnl of distilled water for another hour at 37".…”

“…The cryoglobulins were analyzed for total protein, immunoglobulin content (IgG, IgM, and IgA), and complement components (Clq and C3). The reliability of these detection methods has been detailed elsewhere, and the prevalence and amount of cryoglobulins have been determined in RA as well as in control populations by choosing the figure of 0.15 mg/ml of protein in the final solution to designate patients with cryoglobulins (8).…”

“…Measurements of serum antigammaglobulin (rheumatoid factor) activity and C3 were carried out using, respectively, the Bentonite flocculation test and radial immunodiffusion as previously described (8).…”