Autoantibodies Recognizing Secondary NEcrotic Cells Promote Neutrophilic Phagocytosis and Identify Patients With Systemic Lupus Erythematosus

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Details zur Publikation

Autorinnen und Autoren: Biermann M, Boeltz S, Pieterse E, Knopf J, Rech J, Bilyy R, Van Der Vlag J, Tincani A, Distler J, Krönke G, Schett G, Herrmann M, Munoz LE
Zeitschrift: Frontiers in Immunology
Jahr der Veröffentlichung: 2018
Band: 9
ISSN: 1664-3224


Abstract

Deficient clearance of apoptotic cells reportedly contributes to the etiopathogenesis of the autoimmune disease systemic lupus erythematosus (SLE). Based on this knowledge, we developed a highly specific and sensitive test for the detection of SLE autoantibodies (AAb) utilizing secondary NEcrotic cell (SNEC)-derived material as a substrate. The goal of the present study was to validate the use of SNEC as an appropriate antigen for the diagnosis of SLE in large cohort of patients. We confirmed the presence of apoptotically modified autoantigens on SNEC (dsDNA, high mobility group box 1 protein, apoptosis-associated chromatin modifications, e.g., histones H3-K27-me3; H2A/H4 AcK8,12,16; and H2B-AcK12). Anti-SNEC AAb were measured in the serum of 155 patients with SLE, 89 normal healthy donors (NHD), and 169 patients with other autoimmune connective tissue diseases employing SNEC-based indirect enzyme-linked immunosorbent assay (SNEC ELISA). We compared the test performance of SNEC ELISA with the routine diagnostic tests dsDNA Farr radioimmunoassay (RIA) and nucleosome-based ELISA (anti-dsDNA-NcX-ELISA). SNEC ELISA distinguished patients with SLE with a specificity of 98.9% and a sensitivity of 70.6% from NHD clearly surpassing RIA and anti-dsDNA-NcX-ELISA. In contrast to the other tests, SNEC ELISA significantly discriminated patients with SLE from patients with rheumatoid arthritis, primary anti-phospholipid syndrome, spondyloarthropathy, psoriatic arthritis, and systemic sclerosis. A positive test result in SNEC ELISA significantly correlated with serological variables and reflected the uptake of opsonized SNEC by neutrophils. This stresses the relevance of SNECs in the pathogenesis of SLE. We conclude that SNEC ELISA allows for the sensitive detection of pathologically relevant AAb, enabling its diagnostic usage. A positive SNEC test reflects the opsonization of cell remnants by AAb, the neutrophil recruitment to tissues, and the enhancement of local and systemic inflammatory responses.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Biermann, Mona
Lehrstuhl für Biochemie und Molekulare Medizin
Distler, Jörg PD Dr.
Heisenberg-Professur für Molekulare Mechanismen der Organfibrose
Herrmann, Martin Prof. Dr.
Medizinische Klinik 3 - Rheumatologie und Immunologie
Knopf, Jasmin
Medizinische Klinik 3 - Rheumatologie und Immunologie
Krönke, Gerhard Prof. Dr. med.
Medizinische Klinik 3 - Rheumatologie und Immunologie
Medizinische Klinik 3 - Rheumatologie und Immunologie
Schett, Georg Prof. Dr. med.
Lehrstuhl für Innere Medizin III


Einrichtungen weiterer Autorinnen und Autoren

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Radboud University Nijmegen


Zitierweisen

APA:
Biermann, M., Boeltz, S., Pieterse, E., Knopf, J., Rech, J., Bilyy, R.,... Munoz, L.E. (2018). Autoantibodies Recognizing Secondary NEcrotic Cells Promote Neutrophilic Phagocytosis and Identify Patients With Systemic Lupus Erythematosus. Frontiers in Immunology, 9. https://dx.doi.org/10.3389/fimmu.2018.00989

MLA:
Biermann, Mona, et al. "Autoantibodies Recognizing Secondary NEcrotic Cells Promote Neutrophilic Phagocytosis and Identify Patients With Systemic Lupus Erythematosus." Frontiers in Immunology 9 (2018).

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Zuletzt aktualisiert 2019-17-04 um 08:17

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