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Published on: September 16, 2017
Effect of cryoglobulin and crystalcryoglobulin on TNF-alpha production by normal human monocytes
Barbara Bucki1, Romuald Champy, Lucille Musset
1Laboratoire de radiologie expérimentale et de physiopathologie articulaire, hĵpital Lariboisière, Assistance publique-hĵpitaux de Paris, AP-HP, France.
Insights
IgG1-kappa cryocrystalglobulin did not affect tumor necrosis factor-alpha (TNF-α) production in human monocytes. Noncrystallized cryoglobulins, however, did increase TNF-α levels, suggesting Fc region changes may alter cryocrystalglobulin activity.
Area of Science:
- Immunology
- Rheumatology
- Molecular Biology
Background:
- Destructive arthropathy can involve cryocrystalglobulin deposition in synovial fluid.
- The proinflammatory role of IgG1-kappa cryocrystalglobulin in arthropathy is not well understood.
Purpose of the Study:
- To investigate the proinflammatory properties of IgG1-kappa cryocrystalglobulin.
- To determine its effect on tumor necrosis factor-alpha (TNF-α) production by human monocytes.
Main Methods:
- Human monocytes were isolated and cultured.
- Monocytes were exposed to cryocrystalglobulin, noncrystallized cryoglobulin, monosodium urate (MSU) crystals, or lipopolysaccharide (LPS).
- Supernatant TNF-α concentrations were measured using ELISA.
Main Results:
- IgG1-kappa cryocrystalglobulin did not stimulate TNF-α production by monocytes.
- Noncrystallized cryoglobulin induced a time- and concentration-dependent increase in TNF-α.
- The TNF-α increase from noncrystallized cryoglobulin was less than that induced by MSU crystals or LPS.
Conclusions:
- IgG1-kappa cryocrystalglobulin lacks direct proinflammatory effects on human monocytes.
- Alterations in the Fc region of the cryocrystalglobulin molecule may account for its lack of TNF-α induction.
Objectives:
We recovered an IgG1-kappa cryocrystalglobulin in synovial fluid and membrane specimens from a patient with destructive arthropathy. In the present study, we investigated its proinflammatory properties by measuring its effects on TNF-alpha production by normal human monocytes.
Materials And Methods:
Normal human monocytes isolated by plastic adhesion were cultured in microtiter plates. Adherent monocytes were cultured for 6, 8, and 24 hours with sterile cryocrystalglobulin (150 microg/mL and 2 mg/mL), type I noncrystallised cryoglobulin (same concentrations), monosodium urate (MSU) crystals (2 mg/mL), LPS (10 microg/mL), or medium alone. Supernatant TNF-a concentrations were assayed using an ELISA.
Results:
Cryocrystalglobulin had no effect on TNF-alpha production by normal human monocytes. Noncrystallised cryoglobulin increased TNF-alpha levels in supernatants in a time-dependent and concentration-dependent fashion. This increase was significantly less marked than the increases achieved with MSU crystals or LPS.
Conclusion:
IgG1kappa cryocrystalglobulin has no effect on TNF-alpha production by normal human monocytes. Fc region changes within the cryocrystalglobulin molecule may explain this finding.
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