IgE and IgE-rheumatoid factors in circulating immune complexes in rheumatoid arthritis.

Merétey, K; Falus, András; Erhardt, C. C.; Maini, R. N.

doi:10.1136/ard.41.4.405

Cited by 39 publications

(13 citation statements)

References 18 publications

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“…Furthermore, previous animal studies have show an arthritogenic potential of IgEmediated activation of mast cells in rat joints (20), together with the detection of specific collagen IgE in a cartilage collageninduced mouse arthritis model (21). In human RA, IgE-RF and anti-collagen II-IgE antibodies were observed in several studies (22)(23)(24). In contrast to these earlier reports, we now show a direct cellular immune response toward citrullinated antigens.…”

Section: Discussioncontrasting

confidence: 53%

Evidence for a functional role of IgE anticitrullinated protein antibodies in rheumatoid arthritis

Schuerwegh¹,

Ioan‐Facsinay²,

Dorjée³

et al. 2010

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

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Rheumatoid arthritis (RA) is a systemic autoimmune disease involving inflammation of the joints. Among the autoantibodies described in RA, anticitrullinated protein antibodies (ACPAs) are highly specific and predictive for RA. In addition, ACPAs have been implicated in the pathogenesis of RA. However, a direct functional response of immune cells from ACPA + RA patients toward citrullinated proteins has not been demonstrated. In this study, we show that exposure to citrullinated antigens leads to activation of basophils from ACPA + RA patients within 20 minutes. This was not observed after exposure of basophils to noncitrullinated control antigens or after stimulation of basophils from ACPA − RA patients and healthy controls. Basophil activation was correlated with the binding of citrullinated proteins to basophils. Furthermore, serum from ACPA + RA patients in contrast to that from ACPA − RA patients could specifically sensitize human FcεRI expressing rat basophil cells (RBL), enabling activation by citrullinated proteins. Mast cell degranulation products such as histamine levels were enhanced in synovial fluid of ACPA + RA patients as compared with ACPA − RA and osteoarthritis patients. In addition, histamine levels in synovial fluid from ACPA + RA patients correlated with IgE levels, suggesting degranulation of mast cells by cross-linking IgE. Immunohistochemistry on synovial biopsies demonstrated an increased number of degranulated CD117 + mast cells in ACPA + RA patients; IgE and FcεRI expression in synovial mast cells from ACPA + RA patients was increased. In conclusion, our results show an immunological response of immune cells from ACPA + RA patients in a citrulline-specific manner. Moreover, these data indicate a role for IgE-ACPAs and FcεRI-positive cells in the pathogenesis of RA.

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Section: Discussioncontrasting

confidence: 53%

Evidence for a functional role of IgE anticitrullinated protein antibodies in rheumatoid arthritis

Schuerwegh¹,

Ioan‐Facsinay²,

Dorjée³

et al. 2010

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

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“…Verification of synovial mast cell counts was obtained by acidic toluidine blue staining of cytospin preparations (Cytospin 11; Shandon, Pittsburgh, PA). The results of our digestion procedure were similar to those reported by other investigators (6,15).…”

Section: Methodssupporting

confidence: 91%

Human Synovial Mast Cell Involvement in Rheumatoid Arthritis and Osteoarthritis. Relationship to Disease Type, Clinical Activity, and Antirheumatic Therapy

Bridges¹,

Malone²,

Jicinsky³

et al. 1991

Arthritis & Rheumatism

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Mast cells were isolated by enzymatic digestion of synovium obtained from 48 patients with rheumatoid arthritis (RA) and 42 patients with osteoarthritis (OA). A significantly lower percentage of stainable synovial mast cells was obtained by tissue digestion from patients with clinically active RA compared with those with less active disease. The 54 patients treated with nonsteroidal antiinflammatory drugs had a significantly lower percentage of stainable synovial mast cells in cell suspension than did the other 36 patients. When anti‐IgE antibody was used as a secretagogue in vitro, significantly greater histamine release was observed from synovial mast cells of RA patients compared with OA patients. Greater histamine release in response to anti‐IgE was observed in the RA patients with more clinically active disease and those who were treated with prednisone, compared with RA patients without these features. Synovial mast cells of RA patients treated with a disease‐modifying antirheumatic drug had a significantly lower mean histamine content than did cells from patients not receiving such treatment. Our data suggest that there are differences between synovial mast cells from tissues of patients with RA and OA and suggest that synovial mast cells may be activated in clinically active RA. In addition, the data indicate an effect of systemic anti‐rheumatic therapy on mast cells isolated from synovium of patients with arthritis.

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“…Later, other investigators reported the existence of anti-IgE antibodies (Ab) also of the IgG class [2][3][4][5][6][7]. These IgG Ab were shown to interfere in the assay of IgE [3] and to be present in immune complexes [4,6,7], Such Ab were most prevalent in patients with extrinsic asthma [4,5,7] and correlated with serum IgE and elicited reversed Prausnitz-Kiistner reactions [5], Even though the observations by Williams et al [1] seemed interesting, nobody has tried to confirm them, probably because of the difficulties related to the as say of IgM Ab. Since we had access to a precise and highly sensitive latex (Lx) agglutination technique, i.e.…”

Section: Introductionmentioning

confidence: 99%

Autoantibodies of the IgM Class against a Human Myeloma Protein IgE(DES). I. Occurrence

Magnusson

Vaerman

1986

Int Arch Allergy Immunol

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We report on the natural occurrence of human serum antibodies with specificity for a human monoclonal myeloma IgE(DES). These antibodies were of the IgM class, based on their susceptibility to reduction, sedimentation in sucrose gradients, gel filtration and inhibition of agglutination by anti-IgM antiserum. Auto-antibody levels were studied in several groups of patients by particle-counting immunoassay using latex particles to which purified monoclonal IgE(DES) was coupled. Only sera of patients suffering from parasitosis had significantly higher levels (p < 0.0005) than those of healthy blood donors. Cord sera had very low levels, followed by an age-dependent increase during early infancy. There was no relation (p > 0.10) between serum IgE and IgM antibody level. On the other hand, significant relations between IgM anti-IgE(DES) levels and serum IgM (p < 0.0005), serum IgA (p < 0.001) and serum IgG (p < 0.05) were observed suggesting that high levels were caused by or related to polyclonal activation of the immune system.

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IgE and IgE-rheumatoid factors in circulating immune complexes in rheumatoid arthritis.

Cited by 39 publications

References 18 publications

Evidence for a functional role of IgE anticitrullinated protein antibodies in rheumatoid arthritis

Evidence for a functional role of IgE anticitrullinated protein antibodies in rheumatoid arthritis

Human Synovial Mast Cell Involvement in Rheumatoid Arthritis and Osteoarthritis. Relationship to Disease Type, Clinical Activity, and Antirheumatic Therapy

Autoantibodies of the IgM Class against a Human Myeloma Protein IgE(DES). I. Occurrence

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