Mast cell numbers and histamine levels in synovial fluids from patients with diverse arthritides

Malone, Daniel G.; Irani, Anne-Marie; Schwartz, Lawrence B.; Barrett, Kim E.; Metcalfe, Dean D.

doi:10.1002/art.1780290803

Cited by 125 publications

(72 citation statements)

References 19 publications

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“…Moreover, a role for mast cells in RA was suggested over 20 years ago after observing a strong positive correlation between mast cell numbers and several inflammatory markers in synovial tissue of RA patients (16). Likewise, it was noted that mast cells numbers are increased in RA synovium (17).…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: 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: Discussionmentioning

confidence: 99%

RETRACTED: 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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“…The release of vasoactive amines and platelet-activating factor may alter synovial tissue to allow access of macromolecules. These may in turn lead to in situ immune complex formation at a subendothelial location, with complement activation and subsequent inflammation (32).…”

Section: Discussionmentioning

confidence: 99%

Anti‐ige autoantibodies in systemic lupus erythematosus

Gruber

Kaufman

Marchese

et al. 1988

Arthritis & Rheumatism

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IgG and IgM autoantibodies directed against IgE were determined in 95 serum samples from 67 patients with systemic lupus erythematosus, by an enzyme-linked immunosorbent assay. IgM anti-IgE autoantibodies were found in 18 patients (27%) and IgG anti-IgE autoantibodies were detected in 23 patients (34%). The specificity of the immunoassay was confirmed by the ability to inhibit binding with IgE myeloma, but not other immunoglobulin isotypes and the demonstration that the reactivity was directed to the Fc E fragment of IgE. The IgG fraction of certain sera with anti-IgE activity was capable of inducing histamine release from control basophils and cutaneous mast cells. Clinical associations with the presence of anti-IgE activity were sought by retrospective chart analysis of 61 patients. Significant correlation was found with articular involvement, lymphadenopathy, and anti-DNA antibodies (P < 0.05). Anti-IgE autoantibodies are observed in a significant number of patients with systemic lupus erythematosus and may contribute to the pathogenesis of the vascular and articular lesions characteristic of this disease.

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“…Numerous cellular participants of innate and adaptive immunity contribute to the pronounced inflammatory processes seen in rheumatoid synovitis. Our group (1)(2)(3)(4) and many other investigators (5)(6)(7)(8)(9)(10)(11)(12)(13)(14) have obtained data implicating a prominent involvement of mast cells (MCs) and their mediators in RA and some animal models of this autoimmune disorder. On a weight basis, tetramer-forming ␤ tryptases (15)(16)(17)(18)(19) are the most abundant proteins present in the secretory granules of human MCs.…”

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confidence: 99%

The mouse mast cell–restricted tetramer‐forming tryptases mouse mast cell protease 6 and mouse mast cell protease 7 are critical mediators in inflammatory arthritis

McNeil

Shin

Campbell

et al. 2008

Arthritis & Rheumatism

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Objective. Increased numbers of mast cells (MCs) that express ␤ tryptases bound to heparin have been detected in the synovium of patients with rheumatoid arthritis (RA). The corresponding tryptases in mice are mouse MC protease 6 (mMCP-6) and mMCP-7. Although MCs have been implicated in RA and some animal models of arthritis, no direct evidence for a MC-restricted tryptase in the pathogenesis of inflammatory arthritis has been shown. We created transgenic mice that lack heparin and different combinations of mMCP-6 and mMCP-7, to evaluate the roles of MCrestricted tryptase-heparin complexes in an experimental model of arthritis.Methods. The methylated bovine serum albumin/ interleukin-1␤ (mBSA/IL-1␤) experimental protocol was used to induce inflammatory monarthritis in different mouse strains. Mice were killed at the time of peak disease on day 7, and histochemical methods were used to assess joint pathology.Results. Arthritis was induced in the knee joints of mBSA/IL-1␤-treated mMCP-6 ؉ /mMCP-7 ؊ and mMCP-6 ؊ /mMCP-7 ؉ C57BL/6 mice, and numerous activated MCs that had exocytosed the contents of their secretory granules were observed in the diseased mice. In contrast, arthritis was markedly reduced in heparindeficient mice and in mMCP-6 ؊ /mMCP-7 ؊ C57BL/6 mice.Conclusion. MC-derived tryptase-heparin complexes play important roles in mBSA/IL-1␤-induced arthritis. Because mMCP-6 and mMCP-7 can compensate for each other in this disease model, the elimination of both tryptases is necessary to reveal the prominent roles of these serine proteases in joint inflammation and destruction. Our data suggest that the inhibition of MC-restricted tryptases could have therapeutic potential in the treatment of RA.Rheumatoid arthritis (RA) is an inflammatory disorder of synovial joints characterized by damage to articular structures due to chronic inflammation of the synovium. Numerous cellular participants of innate and adaptive immunity contribute to the pronounced inflammatory processes seen in rheumatoid synovitis. Our group (1-4) and many other investigators (5-14) have obtained data implicating a prominent involvement of mast cells (MCs) and their mediators in RA and some animal models of this autoimmune disorder. On a weight basis, tetramer-forming ␤ tryptases (15)(16)(17)(18)(19) are the most abundant proteins present in the secretory granules of human MCs. Three ␤ tryptase complementary DNAs (designated hTryptase ␤1, ␤2, and ␤3) have been cloned.

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Mast cell numbers and histamine levels in synovial fluids from patients with diverse arthritides

Cited by 125 publications

References 19 publications

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

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

Anti‐ige autoantibodies in systemic lupus erythematosus

The mouse mast cell–restricted tetramer‐forming tryptases mouse mast cell protease 6 and mouse mast cell protease 7 are critical mediators in inflammatory arthritis

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