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01.12.2017 | Research article | Ausgabe 1/2017 Open Access

Arthritis Research & Therapy 1/2017

B cell epitope of human cytomegalovirus phosphoprotein 65 (HCMV pp65) induced anti-dsDNA antibody in BALB/c mice

Zeitschrift:
Arthritis Research & Therapy > Ausgabe 1/2017
Autoren:
Ao HoHsieh, Chin Man Wang, Yeong-Jian Jan Wu, Albert Chen, Ming-I Chang, Ji-Yih Chen
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s13075-017-1268-2) contains supplementary material, which is available to authorized users.

Abstract

Background

HCMV phosphoprotein 65 (HCMVpp65) is a putative immunogen that acts as an accelerator, inducing autoantibody and exacerbating autoimmune response in susceptible animals. The immunity to pp65336-439 instigates autoimmunity, suggesting that pp65336-439 contains crucial B cell epitope(s) for the development of nephritis. This study narrowed down the target epitope to pp65422-439 for immunization of BALB/c mice and mapping of B cell epitope.

Methods

The target epitope pp65422-439 reactivity and B cell epitope mapping was examined in serum from pp65422-439-immunized mice and patients with systemic lupus erythematosus (SLE). Kidney tissue from immunized mice was examined for signs of immune complex nephritis.

Results

Anti-pp65422-439 antibody in serum either from patients with SLE or from pp65422-439-immunized mice exhibited cross-reactivity to several nuclear components such as double-stranded DNA (dsDNA). Moreover, the pp65422-439-immunized mice developed initial signs of glomerulonephritis such as deposition of immunoglobulin G/M (IgG/IgM) and third complement component (C3). With B cell epitope mapping by pp65422-439-derived decapeptides, one dominant epitope, pp65428-437, was identified in serum from pp65422-439-immunized mice and patients with SLE with anti-pp65422-439 antibody. Epitope spreading from pp65428-437 to pp65430-439 was found in pp65422-439-immunized mice in which we generated monoclonal antibodies to pp65425-434 and pp65430-439. However, dsDNA positive reactivity was exclusively observed in Crithidia luciliae stains with pp65430-439-reactive monoclonal antibody. Additionally, we observed the amelioration of autoimmunity following the elevation of IgM targeting pp65428-437.

Conclusions

Our data suggest that pp65428-437 may be an autoimmune or lupus-prone B cell epitope and may catalyze further epitope spreading for inducing autoantibodies in lupus-susceptible individuals.
Zusatzmaterial
Additional file 1: Figure S1. Detection of IgG against pp65386-439 in serum from patients with SLE, AS, RA and normal controls. (PDF 2112 kb)
13075_2017_1268_MOESM1_ESM.pdf
Additional file 2: Figure S2. Detection of anti-pp65 reactivity from pp65386-403, pp65422-439, SA-C3d and PBS immunized serum. (PDF 1144 kb)
13075_2017_1268_MOESM2_ESM.pdf
Additional file 3: Summary of ANA patterns in mice against cellular components and isotypes of antibody deposition on glomeruli. (PDF 53 kb)
13075_2017_1268_MOESM3_ESM.pdf
Additional file 4: Figure S3. Detection of IgM anti-dsDNA antibodies in PBS, SA-C3d, pp65386-403 and pp65422-439 immunized sera. (PDF 773 kb)
13075_2017_1268_MOESM4_ESM.pdf
Literatur
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