Production of agglutinators and rheumatoid factors in plasma cells of rheumatoid and nonrheumatoid synovial tissues

Fehr, K; Velvart, M.; M, Rauber; Knöpfel, M; Baici, Antonio; Salgam, Prathima; Böni, A

doi:10.1002/art.1780240310

Cited by 37 publications

(11 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the 8 cultures in which IgG-RF was detectable, it represented a mean of 2.6% of the total synthesized IgG. Thus, our data are not in agreement with the results of immunofluorescence studies of synovium (1,6,24), in which IgG-RF was detected by staining in 20-60% of IgG-producing plasma cells. It is unlikely that our assay underestimated the amount of IgG-RF, since the method was standardized against a preparation of polyclonal IgG-RF that had been rigorously purified from the serum of a patient with RA (12).…”

Section: Discussioncontrasting

confidence: 97%

“…They concluded that there is extensive synthesis of self-associating IgG-RF in seropositive and seronegative rheumatoid synovial tissue. Recently, Fehr et a1 (24), using an indirect method of C3 binding and immunofluorescence, reported that 95% of seropositive and 72% of seronegative rheumatoid synovial tissues contained IgG-RF-producing cells, and that RF was produced by 60% of IgG-synthesizing cells and by 51-72% of IgM-producing cells. From these reports, it is evident that existing data are highly variable regarding the quantitation of the synthesis and secretion of IgM-RF and IgG-RF in rheumatoid synovium.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

IgG and IgM rheumatoid factor synthesis in rheumatoid synovial membrane cell cultures

Wernick

Lipsky

Marban-arcos

et al. 1985

Arthritis & Rheumatism

View full text Add to dashboard Cite

The detection of rheumatoid factors (RFs) in synovial membranes and fluids of patients with rheumatoid arthritis (RA) has suggested that local production of these antiimmunoglobulin autoantibodies may have a role in the pathogenesis of synovitis. To quantitate RF synthesis in the rheumatoid synovial membrane, 12 synovial specimens were obtained from patients with seropositive RA, 5 from patients with seronegative RA, and 6 from patients with other arthritides. Single cell suspensions were cultured, and supernatants were analyzed for IgG, IgM, IgG‐RF, and IgM‐RF by solidphase radioimmunoassays. IgM‐RF was detected in all of the 12 seropositive culture supernatants, and IgG‐RF was detected in 8 of the 12. Addition of cycloheximide to the cultures resulted in a ⩾40% decrease in the amount of IgM‐RF. A similar decrease in IgG‐RF occurred in the 4 cultures in which the largest amounts of IgG‐RF were detected. IgM‐RF synthesis represented 7.3 ± 0.7% (mean ± SEM) of the total IgM produced, and IgG‐RF represented 2.6 ± 1.1% (mean ± SEM) of the IgG synthesized in those cultures with detectable IgG‐RF. Cultures of synovial membrane cells (SMC) from seronegative RA patients or patients with other arthritides did not contain detectable amounts of IgM‐RF or IgG‐RF. Selective synthesis of RF by seropositive synovium was suggested by the observation that the fractions of synthesized IgM with RF activity were greater in the SMC supernatants than in paired sera in all cases, and the fractions of IgG with RF activity were greater in the SMC supernatants of 3 of the 4 cases in which substantial amounts of IgG‐RF were produced. Comparison of the percentages of newly synthesized IgM with RF activity in paired cultures of SMC and peripheral blood mononuclear cells similarly indicated selective synthesis of IgM‐RF by the synovium. These results demonstrate active and selective synthesis of both IgG‐RF and IgM‐RF by seropositive SMC. However, RFs account for only a minor fraction of the total Ig produced.

show abstract

Section: Discussioncontrasting

confidence: 97%

Section: Discussionmentioning

confidence: 99%

IgG and IgM rheumatoid factor synthesis in rheumatoid synovial membrane cell cultures

Wernick

Lipsky

Marban-arcos

et al. 1985

Arthritis & Rheumatism

View full text Add to dashboard Cite

show abstract

“…RF is also produced and concentrated in the rheumatoid synovial tissue (23)(24)(25)(26)(27)(28). IgG1, the dominant ACPA isotype, is recognized by all of the so far described RA-derived RF (29).…”

mentioning

confidence: 99%

IgM and IgA Rheumatoid Factors Purified from Rheumatoid Arthritis Sera Boost the Fc Receptor– and Complement-Dependent Effector Functions of the Disease-Specific Anti–Citrullinated Protein Autoantibodies

Anquetil

Clavel

Offer

et al. 2015

The Journal of Immunology

109

View full text Add to dashboard Cite

Rheumatoid factors (RF) and the disease-specific anti–citrullinated protein autoantibodies (ACPA) coexist in the joints of rheumatoid arthritis (RA) patients where they probably contribute to synovitis. We investigated the influence of IgM and IgA RF on the FcR- and complement-dependent effects of ACPA immune complexes (ACPA-IC). When stimulated by ACPA-IC formed in the presence of IgM RF or IgA RF fractions purified from RA serum pools, M-CSF–generated macrophages skewed their cytokine response toward inflammation, with increases in the TNF-α/IL-10 ratio and in IL-6 and IL-8 secretion, and decreases in the IL-1Ra/IL-1β ratio. In the IgM RF-mediated amplification of the inflammatory response of macrophages, the participation of an IgM receptor was excluded, notably by showing that they did not express any established receptor for IgM. Rather, this amplification depended on the IgM RF-mediated recruitment of more IgG into the ACPA-IC. However, the macrophages expressed FcαRI and blocking its interaction with IgA inhibited the IgA RF-mediated amplification of TNF-α secretion induced by ACPA-IC, showing its major implication in the effects of RF of the IgA class. LPS further amplified the TNF-α response of macrophages to RF-containing ACPA-IC. Lastly, the presence of IgM or IgA RF increased the capacity of ACPA-IC to activate the complement cascade. Therefore, specifically using autoantibodies from RA patients, the strong FcR-mediated or complement-dependent pathogenic potential of IC including both ACPA and IgM or IgA RF was established. Simultaneous FcR triggering by these RF-containing ACPA-IC and TLR4 ligation possibly makes a major contribution to RA synovitis.

show abstract

“…Limited proteolysis of IgGs creates new antigenic sites (Fehr, 1971). Antibodies to the neoepitopes created by limited cleavage of human IgG by a variety of proteinases are found in human serum and these can be elevated in some auto-immune disorders, including arthritis (Fehr, 1971(Fehr, , 1981. Whether these will react with cleavage neoantigens on murine Igs, and what effect such reaction might have on the development of the immune response to parenteral use of a murine monoclonal antibody is unknown.…”

Section: Discussionmentioning

confidence: 99%

A novel acid proteinase relased by hybridoma cells

1990

View full text Add to dashboard Cite

An acid proteinase has been detected in culture supernate of the 9.2.27 murine hybridoma. This enzyme extensively degrades albumin and transferrin during short incubations at pH 3 and below. Limited proteolysis of the 9.2.27 IgG2a appears to occur in the culture supernate. Proteolysis in enhanced at low pH in the presence of urea or 1 M acetic acid. The proteinase activity accumulates in continuous perfusion, total cell recycle cultures, beginning during exponential growth of the hybridoma. It is destroyed by boiling and blocked by pepstatin, but not by inhibitors of cysteine or serine proteinases or by EDTA. The low pH optimum may distinguish this enzyme from the known rat and mouse aspartic acid proteinases including cathepsin D and cathepsin E.

show abstract

Production of agglutinators and rheumatoid factors in plasma cells of rheumatoid and nonrheumatoid synovial tissues

Cited by 37 publications

References 18 publications

IgG and IgM rheumatoid factor synthesis in rheumatoid synovial membrane cell cultures

IgG and IgM rheumatoid factor synthesis in rheumatoid synovial membrane cell cultures

IgM and IgA Rheumatoid Factors Purified from Rheumatoid Arthritis Sera Boost the Fc Receptor– and Complement-Dependent Effector Functions of the Disease-Specific Anti–Citrullinated Protein Autoantibodies

A novel acid proteinase relased by hybridoma cells

Contact Info

Product

Resources

About