In vitro synthesis of IgM and IgM rheumatoid factor in seronegative arthritides

1984 ◽  
Vol 4 (2) ◽  
pp. 49-53 ◽  
Author(s):  
G. S. Alarcón ◽  
W. J. Koopman ◽  
R. E. Schrohenloher
2014 ◽  
Vol 74 (7) ◽  
pp. 1425-1431 ◽  
Author(s):  
Lætitia Laurent ◽  
Florence Anquetil ◽  
Cyril Clavel ◽  
Ndiémé Ndongo-Thiam ◽  
Géraldine Offer ◽  
...  

ObjectivesAnticitrullinated protein antibodies (ACPA) are specifically associated with rheumatoid arthritis (RA) and produced in inflamed synovial membranes where citrullinated fibrin, their antigenic target, is abundant. We showed that immune complexes containing IgG ACPA (ACPA-IC) induce FcγR-mediated tumour necrosis factor (TNF)-α secretion in macrophages. Since IgM rheumatoid factor (RF), an autoantibody directed to the Fc fragment of IgG, is also produced and concentrated in the rheumatoid synovial tissue, we evaluated its influence on macrophage stimulation by ACPA-IC.MethodsWith monocyte-derived macrophages from more than 40 healthy individuals and different human IgM cryoglobulins with RF activity, using a previously developed human in vitro model, we evaluated the effect of the incorporation of IgM RF into ACPA-IC.ResultsIgM RF induced an important amplification of the TNF-α secretion. This effect was not observed in monocytes and depended on an increase in the number of IgG-engaged FcγR. It extended to the secretion of interleukin (IL)-1β and IL-6, was paralleled by IL-8 secretion and was not associated with overwhelming secretion of IL-10 or IL-1Ra. Moreover, the RF-induced increased proinflammatory bioactivity of the cytokine response to ACPA-IC was confirmed by an enhanced, not entirely TNF-dependent, capacity of the secreted cytokine cocktail to prompt IL-6 secretion by RA synoviocytes.ConclusionsBy showing that it can greatly enhance the proinflammatory cytokine response induced in macrophages by the RA-specific ACPA-IC, these results highlight a previously undescribed, FcγR-dependent strong proinflammatory potential of IgM RF. They clarify the pathophysiological link between the presence of ACPA and IgM RF, and RA severity.


2011 ◽  
Vol 70 (Suppl 2) ◽  
pp. A38-A38
Author(s):  
L. Laurent ◽  
C. Clavel ◽  
F. Anquetil ◽  
J.-L. Pasquali ◽  
M. Sebbag ◽  
...  

1983 ◽  
Vol 27 (1) ◽  
pp. 96-109 ◽  
Author(s):  
Martin A. Rodriguez ◽  
Arthur D. Bankhurst ◽  
Ralph C. Williams ◽  
Gary M. Troup ◽  
Peter Stastny

Parasitology ◽  
1990 ◽  
Vol 101 (2) ◽  
pp. 177-185 ◽  
Author(s):  
M. K. Stuart ◽  
T. J. Green

Monoclonal IgM rheumatoid factor-like anti-globulins were produced byin vitrostimulation of naive BALB/c spleen cells with lipopolysaccharide, and by hyperimmunization of mice with merozoites ofPlasmodium falciparum, followed by fusion of the spleen cells to mouse myelomas.In vitro, these anti-globulins augmented the inhibitory effects ofP. falciparum-specific polyclonal mouse sera and monoclonal IgG1 and IgG2b antibodies by binding to Fc fragments of IgG molecules attached to blood-stage parasites. In some instances, the presence of anti-globulins correlated with an increase in the number of schizonts which failed to disperse merozoites. In other cases, parasitaemia remained low in the absence of the schizont inhibition phenomenon, suggesting that anti-globulins contribute to host cell protection not only by agglutinating merozoites, but also by increasing the density of the antibody coat surrounding the parasites, thus interfering with parasite receptor-erythrocyte ligand interactions. The anti-globulins were not inhibitory when added to parasite cultures containing IgG not specific for P. falciparum. These results may help explain the function of IgM anti-globulins found at elevated serum levels in some patients with malaria or other chronic infectious diseases.


1983 ◽  
Vol 26 (9) ◽  
pp. 1091-1097 ◽  
Author(s):  
Martin A. Rodriguez ◽  
William A. Prinz ◽  
Wilmer L. Sibbitt ◽  
Arthur D. Bankhurst ◽  
Ralph C. Williams

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