Date: Sunday, November 8, 2015
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Various autoantibodies have been identified in cerebrospinal fluids (CSF) of neuropsychiatric systemic lupus erythematosus (NPSLE). They are supposed to form immune complex with complement to induce inflammatory responses. We therefore measured the 3rd component of complement (C3) and other inflammation-related molecules in CSF of NPSLE patients.
Methods: This study included 51 SLE patients. According to the 1999 ACR definition criteria, 43 patients were diagnosed with NPSLE whereas 8 patients were diagnosed with non-NPSLE. We measured levels of C3, alpha-2-Macroglobulin (α2MG) and IL-6, in CSF or serum by sandwich ELISA.
Results: Quantitative ELISA revealed that the IL-6 levels in CSF of NPSLE (441.9 ± 1233 pg/ml) were significantly higher than that of non-NPSLE (3.36 ± 2.58 pg/ml) (p = 0.0010), which is consistent with the previous observation reported by Hirohata et al. (Clin Rheumatol. 2009). IL-6 is a primary cytokine, which induces various inflammatory responses including complement activation. We examined C3 expression in CSF of NPSLE patients. C3 levels in CSF of NPSLE (4.94 ± 3.79 µg/ml) were significantly higher than that of non-NPSLE (1.92 ± 1.14 µg/ml) (p = 0.0071). It is possible that elevation of C3 in CSF is due to upregulation of serum C3. We therefore analyzed serum levels of C3. No significant difference in serum C3 levels was observed between NPSLE (645 ± 311 µg/ml) and non-NPSLE (824 ± 374 µg/ml) (p = 0.2767). In addition, correlation of C3 levels between CSF and serum was weak in NPSLE (r = 0.2885, p = 0.0380), suggesting that upregulation of C3 in CSF is independent of C3 levels in serum. Another inflammatory protein we analyzed was α2MG, which is a protease inhibitor for localizing proteolytic responses in the inflammatory focus. Quantitative ELISA revealed that levels of α2MG in NPSLE (2.90 ± 3.69 µg/ml) were significantly higher than that of non-NPSLE (0.72 ± 0.26 µg/ml) (p = 0.0010). In contrast, serum levels of α2MG were similar in both specimens. Correlation of α2MG levels between CSF and serum was weak (r = 0.2582, p = 0.0674), suggesting independence of α2MG concentration between CSF and serum. It was notable that CSF levels of C3 and α2MG showed strong correlation (r = 0.6990, p < 0.0001). In addition, that CSF levels of IL-6 was correlated with that of C3 and α2MG, (r = 0.5102, p = 0.0003) and (r = 0.5662, p < 0.0001), respectively, suggesting that IL-6 upregulates C3 and α2MG in CSF.
Conclusion: We demonstrated the increase of IL-6 in CSF of NPSLE patients. IL-6 may upregulate C3 and α2MG in CSF as “local” inflammatory response.
To cite this abstract in AMA style:Asano T, Sato S, Kobayashi H, Kariya Y, Ito H, Hoshi K, Yoshihara A, Ugawa Y, Takahashi M, Sekine H, Hirohata S, Watanabe H, Ohira H, Hashimoto Y. Upregulation of Complement C3 and Alpha-2-Macroglobulin in Cerebrospinal Fluid of Neuropsychiatric Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/upregulation-of-complement-c3-and-alpha-2-macroglobulin-in-cerebrospinal-fluid-of-neuropsychiatric-systemic-lupus-erythematosus/. Accessed June 3, 2020.
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