Synovial Fluid IgG Research Articles

The presence of citrullinated proteins is not specific for rheumatoid synovial tissue

Antibodies directed toward citrullinated proteins (e.g., anti-cyclic citrullinated peptide antibodies) are highly specific for rheumatoid arthritis (RA) and are produced locally at the site of inflammation. Although the presence of citrullinated proteins in rheumatoid synovium has been described in the literature, it is uncertain whether their presence is specific for RA. The present study was undertaken to investigate this. The local production of the anti-citrullinated protein antibodies was investigated by comparing the concentration of the antibodies (corrected for the total amount of IgG present) in paired samples of serum and synovial fluid from RA patients. The presence of citrullinated proteins in the synovial tissue was investigated by immunohistochemical analysis of synovial tissue from RA patients and from patients with other arthropathies, using a variety of specific antibodies to citrullinated proteins. In RA patients, anti-citrullinated protein antibodies constituted a 1.4-fold higher proportion of IgG in synovial fluid compared with serum, which is indicative of a local production of the antibodies. Immunohistochemical staining of citrullinated proteins was observed in the lining layer, the sublining layer, and in extravascular fibrin deposits in inflamed synovial tissue from RA as well as non-RA patients. The presence of citrullinated proteins in the inflamed synovium is not specific for RA, but rather, it may be an inflammation-associated phenomenon. The high specificity of the anti-citrullinated protein antibodies is, therefore, most likely the result of an abnormal humoral response to these proteins.

Elevated levels of synovial fluid antibodies reactive with the small proteoglycans biglycan and decorin in patients with rheumatoid arthritis or other joint diseases.

To determine whether patients with rheumatoid arthritis (RA) express humoral immunity to the small proteoglycans biglycan and decorin and to compare the response to that of patients suffering from other joint diseases. Serum and synovial fluid IgG and IgM antibody levels were determined by enzyme-linked immunosorbent assay. Antibodies to biglycan and decorin as well as to other known and extensively investigated cartilage matrix components such as type II collagen, aggrecan and fibronectin were investigated. Patients suffering from RA, osteoarthritis (OA), psoriatic arthritis and other seronegative spondylarthropathies were included in the study. Correlation between antibody levels and clinical/laboratory parameters was determined. Patients with RA expressed an increased humoral immunity to biglycan, while patients with seronegative spondylarthropathies displayed elevated decorin-specific synovial antibody levels compared with OA patients. These results indicate a significantly higher immunity to small proteoglycans in RA and seronegative spondylarthropathies than in OA suggesting a possible involvement in the pathogenesis of inflammatory rheumatic diseases.

The C1q binding activity of IgG is modified in vitro by reactive oxygen species: implications for rheumatoid arthritis

IgG can be denatured in vitro by reactive oxygen species (ROS). Native IgG activates the complement cascade through C1q. Using a modified ELISA, C1q binding activity of rheumatoid IgG has been compared to IgG denatured by neutrophil-derived ROS. The C1q binding activity of rheumatoid synovial fluid IgG is greater than the corresponding serum IgG ( P < 0.01). Denaturation of IgG by activated polymorphs or the Fenton reaction decreased its C1q binding activity ( P < 0.01). In vitro exposure of IgG to OH · and ROO · increased its interaction with C1q ( P < 0.01). Hypochlorous acid had no effect. ROS-induced alteration to IgG-C1q binding activity may promote the inflammatory response in rheumatoid arthritis.

Antikeratin antibodies in synovial fluid in rheumatoid arthritis

Serum and synovial fluid of 20 patients with classical or definite rheumatoid arthritis (RA) were tested for antikeratin antibodies (AKA) by indirect immunofluorescence using rat esophagus as antigen. AKA were found in 80% of the RA patients, in serum as well as in synovial fluid. None of the 54 serum control patients were AKA positive in serum. None of the 17 synovial fluid control patients were AKA positive in synovial fluid. F(ab)'2 fragments prepared from AKA positive RA serum retained antibody activity. AKA belonged to the IgG class of immunoglobulins. Corrected for the lower IgG content in synovial fluid, AKA constituted a higher percentage of the IgG in synovial fluid than in serum. This could imply a possibility of local production of AKA in the joint.

Rheumatoid factor has increased reactivity with IgG from synovial fluids of patients with rheumatoid arthritis and osteoarthritis.

Synovial fluid IgG may be altered in rheumatoid arthritis (RA) and promote the formation of immune complexes with rheumatoid factor. To investigate this possibility, monomeric IgG was prepared from synovial fluids from a range of arthritides for use as the antigen in a rheumatoid factor microplate radioimmunoassay. In comparisons with normal serum IgG antigen, increased rheumatoid factor binding was shown to IgG antigens prepared from synovial fluids from patients with RA and osteoarthritis (OA). Increased binding was also shown to RA sera IgG, but not to OA sera IgG. This increased binding was not due to increased IgG antigen binding to the plate or to IgG rheumatoid factor in the antigen preparations. It was considered that cause was a structural alteration of the IgG as a result of inflammation within the rheumatoid and OA joint.

Effects of gold therapy on the synthesis and quantity of serum and synovial fluid IgM, IgG, and IgA rheumatoid factors in rheumatoid arthritis patients.

Eleven patients with active rheumatoid arthritis were monitored prospectively while receiving up to 1 gm of gold sodium thiomalate. There was a significant decrease in serum and synovial fluid IgG, IgA, and IgM rheumatoid factor (RF) levels over the period of study. Comparison of changes in serum RF and total immunoglobulin levels indicated a selective effect on RF production. These observations were supported by changes in the spontaneous in vitro production of IgM-RF and total IgM by peripheral blood mononuclear cells. Studies of synovial membrane synthesis showed a downward trend in immunoglobulin and RF production, but this did not reach statistical significance. A differential effect on the various RF classes was also noted. The most profound effect was on IgM-RF production; whereas, changes in IgG-RF production were least affected. These results suggest a selective and differential effect of gold salts on RF production.

Cell-Mediated Immunity in Rheumatoid Arthritis

Leucocyte migration inhibition (LMI) by paired samples of autologous serum and synovial fluid IgG as well as homologous IgG and also heat-aggregated forms of all three IgGs was studied for patients with rheumatoid arthritis (RA) and compared with the response to these antigens by leucocytes from healthy individuals. Autologous and homologous serum IgGs did not markedly affect leucocyte migration, whereas synovial fluid IgGs caused occasional pronounced LMI with autologous (rheumatoid) leucocytes. Although aggregated IgG produced LMI in both RA patients and controls, the means of the migration indexes were significantly different between both groups. Peripheral blood mononuclear cells from RA patients and healthy controls were also cultured with both native rheumatoid and normal IgG; only supernatants from RA cells incubated with rheumatoid IgG showed LMI activity, in contrast to the other culture supernatants. These results indicate that LMI to native IgG in RA may represent a form of specific cell-mediated immunity, although LMI to aggregated IgG might be explained by non-specific factors.

IgG subclass composition of rheumatoid arthritic sera and joint fluids.

The IgG subclass composition of 24 matched pairs of synovial fluids and sera, from 24 patients with rheumatoid arthritis, was determined. The subclass composition of rheumatoid synovial fluid IgG was found to be qualitatively the same as that of the corresponding serum, differing only in certain quantitative aspects. A 7-8% increase in IgG1 level found in the sera of rheumatoid arthritis patients relative to that in the sera of normal individuals was accompanied by 6-8, 0-7, and 0-3% decreases in IgG2, IgG3, and IgG4, respectively.

Serum and synovial fluid IgG, IgA and IgM antigammaglobulins in rheumatoid arthritis.

AbstractAntigammaglobulins of IgG, IgA and IgM classes were measured in normal individuals and in patients with osteoarthritis or rheumatoid arthritis. Serum IgG and IgA and synovial fluid IgG antigammaglobulin levels were significantly higher in patients with rheumatoid arthritis than in other individuals, with highest levels occurring in patients with positive latex fixation tests. IgM antigammaglobulins were elevated only in patients with latex positive rheumatoid arthritis. Increased serum levels of IgG, IgA and IgM antigammaglobulins were each associated with clinical findings of severe rheumatoid arthritis. Increased levels of serum and synovial fluid IgG and IgM antigammaglobulins were each associated with diminished serum and synovial fluid complement levels.

IMMUNOREACTANTS IN RHEUMATOID SYNOVIAL EFFUSIONS

Measurements were made of the IgG in synovial fluid which is synthesized by the intact rheumatoid synovium. In five rheumatoid subjects 12-24% of the IgG present in their synovial fluid was derived from local production. No evidence for local production was found in patients with degenerative arthritis or Reiter's syndrome. It was estimated that as much as 95 mg of IgG was produced by the synovium of a single knee joint daily. Rheumatoid inflammation is associated with the presence of large numbers of white blood cells, predominantly polymorphonuclear, in the articular cavity. Each day as many as one billion white cells enter the articular cavity to participate in this inflammatory response. Factors causing the directed migration of polymorphonuclear leukocytes were found in the majority of rheumatoid effusions studied. The chemotactic activity is, in large part, related to the fifth (C5) and sixth (C6) components of human complement. Physical-chemical techniques indicate that the activity is attributable to C 567 and C5a, a cleavage product of C5. In addition to the presence of preformed chemotactic factors, more than half of the rheumatoid fluids contain an enzyme capable of generating chemotactic activity from the fifth component (C5) of human complement. This information supports the concept that rheumatoid joint inflammation is an example of immune complex disease in which a significant proportion of the immunoreactants are derived from local production.