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. 2017 Nov 6:14:24.
doi: 10.1186/s12950-017-0171-6. eCollection 2017.

Detection of circulating natural antibodies to inflammatory cytokines in type-2 diabetes and clinical significance

Weiyi Cai #  1 , Cailing Qiu #  2 , Hongyu Zhang  3 , Xiangyun Chen  2 , Xuan Zhang  3 , Qingyong Meng  1 , Jun Wei  4
Affiliations

Detection of circulating natural antibodies to inflammatory cytokines in type-2 diabetes and clinical significance

Weiyi Cai et al. J Inflamm (Lond). .

Abstract

Background: Inflammatory cytokines have been demonstrated to be involved in developing insulin resistance and type-2 diabetes (T2D). Natural antibodies in the circulation have protective effects on common diseases in humans. The present study was thus designed to test the hypothesis that natural antibodies against inflammatory cytokines could be associated with T2D.

Methods: An enzyme-linked immunosorbent assay (ELISA) was developed in-house to detect plasma IgG against peptide antigens derived from interleukin 1α (IL1α), IL1β, IL6, IL8 and tumor necrosis factor-α (TNF-α) in 200 patients with T2D and 220 control subjects.

Results: Binary regression showed that compared with control subjects, T2D patients had a decreased level of plasma anti-IL6 IgG (adjusted r2=0.034, p=0.0001), anti-IL8 IgG (adjusted r2=0.021, p=0.002) and anti-TNF-α IgG (adjusted r2=0.017, p=0.003). Female patients mainly contributed to decreased levels of anti-IL6 IgG (adjusted r2=0.065, p=0.0008) and anti-IL8 IgG (adjusted r2=0.056, p=0.003), while male patients mainly contributed to decreased anti-TNF-α IgG levels (adjusted r2=0.024, p=0.005). ROC curve analysis revealed a sensitivity of 16.5% against specificity of 95.5% for anti-IL6 IgG assay and a sensitivity of 19.5% against specificity of 95.9% for anti-IL8 IgG assay. Glycated hemoglobin levels measured after 6-month glucose-lowering treatment appeared to be inversely correlated with plasma anti-IL1α IgG (r=-0.477, df=17, p=0.039) and anti-IL6 IgG (r=-0.519, df=17, p=0.023) although such correlation failed to survive the Bonferroni correction.

Conclusions: Deficiency of natural IgG against inflammatory cytokines is likely to be a risk factor for T2D development and detection of such antibodies may be useful for personalized treatment of the disease.

Keywords: ELISA; IgG antibody; Inflammatory cytokines; Natural antibodies; Type-2 diabetes.

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Conflict of interest statement

Ethics approval and consent to participate

This work was approved by the Institutional Review Board of the Second Hospital of Jilin University, Changchun, China, (IRB#: SHJU2017-101), and performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.

Consent for publication

Not applicable.

Competing interests

All authors declared that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
ROC curve analysis of circulating IgG against inflammatory cytokines in T2D. Anti-IL1α IgG had an AUC of 0.564 (95% CI 0.509-0.619) with sensitivity of 13.0% against a specificity of 95.0%; anti-IL1β IgG had an AUC of 0.544 (95% CI 0.489-0.599) with sensitivity of 10.0% against a specificity of 95.0%; anti-IL6 IgG had an AUC of 0.601 ( 95% CI 0.547-0.655) with sensitivity of 16.5% against a specificity of 95.5%; anti-IL8 IgG had an AUC of 0.593 (95%CI 0.538-0.647) with sensitivity of 19.5% against a specificity of 95.9%; anti-TNF-α IgG had an AUC of 0.589 (95%CI 0.534-0.643) with sensitivity of 4.5% against a specificity of 95.0%
Fig. 2
Fig. 2
Correlation between the duration of T2D and the levels of circulating IgG against inflammatory cytokines a. IL1α IgG : r = -0.148, df =199, p= 0.037; b. IL1β IgG: r = -0.085, df = 199, p= 0.234; c. IL6 IgG: r = 0.04, df =199, p= 0.576; d. IL8 IgG: r = 0.047, df = 199, p= 0.508; e. TNF-α IgG: r = -0.083, df = 199, p= 0.242
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