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FRI0016 IGE as a Biomarker of Regulatory T Cell Activity in Autoimmune Diseases
  1. M.F. Moraes-Fontes1,2,
  2. N. Costa1,
  3. C. Santos3,
  4. A. Coutinho1,
  5. C. Fesel1
  1. 1Lupus and Autoreactive Immune Repertoires, Instituto Gulbenkian de Ciência, Oeiras
  2. 2Autoimmune Disease Unit
  3. 3Immunology Laboratory, Hospital Curry Cabral, Lisbon, Portugal

Abstract

Background Regulatory T cell (Treg) defects are associated with autoimmune diseases [1]. Immunoglobulin E (IgE) is elevated in primary immunodeficiencies associated to Regulatory T cell (Treg) defects [2] and is known to be positively correlated to disease activity in Systemic Lupus Erythematosus (SLE) [3,4]. More specifically, Treg frequency (increased) and CD25 expression (decreased) are dissociated in patients with active SLE [5,6].

Objectives To establish the relationship between circulating Treg frequency/number and phenotype and total IgE/IgE auto-antibodies and test the hypothesis that total IgE could be a marker of a generalized Treg deficit.

Methods We first tested a large cross-sectional collection of plasma samples from unselected patients with a diagnosis of SLE according to ACR criteria (n=123) and from healthy controls (n=153). We then started a prospective longitudinal study of SLE patients (n=33, 30 females, mean age 41±10 years). A median of 4 samples were obtained per patient. Clinical characteristics, SLEDAI 2 K as index of disease activity, SELENA-SLEDAI score for definition of flare and sample collection were undertaken. During follow-up 13/33 patients experienced a flare. Samples were analysed by an ELISA “in house” method optimized for total IgE, antigen-specific IgE (anti-DNA, Sm, RNP), IgG anti-DNA and IgG anti-Sm. FACS analysis determined Treg frequency (CD4+CD45RO+Foxp3high) and CD25 MFI expression. The Mann-Whiney Test and Spearman correlation were used with values of p<0.05 considered significant.

Results While there was no significant difference in total IgE, IgE anti-DNA was higher in patients (p=0.02) and positively correlated with SLEDAI (p=0.009). In the longitudinal prospective collection there was a positive correlation between IgG anti-DNA (p=0.002) or IgE anti-DNA (p=0.0003) and disease activity. IgE anti-DNA was increased in some patients with high SLEDAI and no IgG anti-DNA. The frequency of active Treg was positively correlated with SLEDAI (p=0.006) and with IgG anti-DNA (p=0.0004) while their CD25 expression was negatively correlated with SLEDAI (p=0.008) and IgG anti-DNA (p=0.002). There was no association between total IgE or IgE anti-DNA and Treg frequency or CD25 expression in either the cross-sectional study or the longitudinal patient collection.

Conclusions These results indicate that unlike IgG anti-DNA, IgE anti-DNA is not associated with Treg frequency or CD25 expression, raising questions regarding its affinity and pathogenicity. Still, as previously described, IgE anti-DNA behaved as a biomarker of SLE disease activity. In this study we demonstrate that it may be a useful biomarker in the absence of IgG anti-DNA.

References

  1. Bennett Nat Genet 2001 27(1):20-1.

  2. Ozcan J Allergy Clin Immunol 2008. 122(6):1054-62.

  3. Charles Nat Med 2010 16(6):701-7.

  4. Dema Plos One 2014 9(2)e90424.

  5. Bonelli Ann Rheum Dis 2008 67(5):664-71.

  6. Suen Immunology 2009 127(2):196-205.

Acknowledgements Jocelyne Demengeot (JD) for grant submission and ongoing support, JD, W Haas and J Lafaille for helpful discussions and R van Vollenhoven for scientific input. Staff at UIC and ICBAS (Porto), HSM, CHLO, Santarém, HFF, HCC and Patients and Patient Association for sample collections. Funding FCT EXPL/DTP-PIC/0644/2012

Disclosure of Interest None declared

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