Characterization of discriminant human brain antigenic targets in neuropsychiatric systemic lupus erythematosus using an immunoproteomic approach

Authors

  • Didier Lefranc,

    Corresponding author
    1. Laboratoire d'Immunologie EA 2686, IMPRT-IFR 114, Université Lille 2, Lille, France
    • Laboratoire d'Immunologie, Faculté de Médecine–Pôle Recherche, 1 Place de Verdun, 59045 Lille Cedex, France
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    • Drs. Lefranc and Launay contributed equally to this work.

  • David Launay,

    1. Laboratoire d'Immunologie EA 2686, IMPRT-IFR 114, Hôpital Claude-Huriez, Université Lille 2, and Centre Hospitalier Régional Universitaire de Lille, Lille, France
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    • Drs. Lefranc and Launay contributed equally to this work.

  • Sylvain Dubucquoi,

    1. Laboratoire d'Immunologie EA 2686, IMPRT-IFR 114, Université Lille 2, Lille, France
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  • Jérôme De Seze,

    1. Laboratoire d'Immunologie EA 2686, IMPRT-IFR 114, Hôpital Roger Salengro, Université Lille 2, and Centre Hospitalier Régional Universitaire de Lille, Lille, France
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  • Patricia Dussart,

    1. Laboratoire d'Immunologie EA 2686, IMPRT-IFR 114, Université Lille 2, Lille, France
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  • Marie Vermersch,

    1. Laboratoire d'Immunologie EA 2686, IMPRT-IFR 114, Université Lille 2, Lille, France
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  • Eric Hachulla,

    1. Hôpital Claude-Huriez, Université Lille 2, and Centre Hospitalier Régional Universitaire de Lille, Lille, France
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  • Pierre-Yves Hatron,

    1. Hôpital Claude-Huriez, Université Lille 2, and Centre Hospitalier Régional Universitaire de Lille, Lille, France
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  • Patrick Vermersch,

    1. Laboratoire d'Immunologie EA 2686, IMPRT-IFR 114, Hôpital Roger Salengro, Université Lille 2, and Centre Hospitalier Régional Universitaire de Lille, Lille, France
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  • Luc Mouthon,

    1. Université Paris Descartes, UPRES-EA 4058, and Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France
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    • Dr. Mouthon has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Actelion, Pfizer, and LFB.

  • Lionel Prin

    1. Laboratoire d'Immunologie EA 2686, IMPRT-IFR 114, Université Lille 2, Lille, France
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Abstract

Objective

To characterize discriminant human brain antigenic targets in patients with neuropsychiatric systemic lupus erythematosus (NPSLE), using a standardized immunoproteomic approach.

Methods

Self-IgG reactivity against normal and injured human brain tissues was studied by Western blotting of sera from 169 subjects, 16 patients with NPSLE, 12 patients with SLE without neuropsychiatric manifestations (non-NPSLE), 32 patients with Sjögren's syndrome with or without central nervous involvement, 82 patients with multiple sclerosis, and 27 healthy subjects. A proteomic approach was then applied to characterize discriminant antigens identified after comparisons of all patterns.

Results

The serum self-IgG reactivity patterns against human brain tissue differed significantly between patients with NPSLE and the control groups. Four normal brain antigenic bands were specifically or preferentially recognized by sera from NPSLE patients (p240, p90, p77, and p24). Protein band p240 was characterized as microtubule-associated protein 2B (MAP-2B), p77 as Hsp70–71, and p24 as triosephosphate isomerase. Protein band p90 was not characterized. In contrast, 1 other protein band (p56, characterized as septin 7) was never recognized by sera from NPSLE patients but was recognized by a majority of sera from non-NPSLE patients.

Conclusion

Our findings show that the immunoproteomic approach is a reliable method for assessing serum self-IgG reactivities against human brain tissue in NPSLE. Our characterization of some of the identified discriminant antigens, such as MAP-2B, triosephosphate isomerase, and septin 7, suggests that the stability of neuronal microtubules might be involved in the pathophysiology of NPSLE.

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