Author dc.contributor.author | Prechl, József | |
Author dc.contributor.author | Papp, Krisztián | |
Author dc.contributor.author | Z, Herincs | |
Author dc.contributor.author | H, Peterfy | |
Author dc.contributor.author | Lóránd, Veronika | |
Author dc.contributor.author | Szittner, Zoltán | |
Author dc.contributor.author | Czirják, László | |
Availability Date dc.date.accessioned | 2016-04-11T11:44:47Z | |
Availability Date dc.date.available | 2016-04-11T11:44:47Z | |
Release dc.date.issued | 2016 | |
Issn dc.identifier.issn | 1932-6203 | |
uri dc.identifier.uri | http://hdl.handle.net/10831/30149 | |
Abstract dc.description.abstract | Systemic lupus erythematosus is a chronic autoimmune disease with multifactorial ethiopathogenesis. The complement system is involved in both the early and late stages of disease development and organ damage. To better understand autoantibody mediated complement consumption we examined ex vivo immune complex formation on autoantigen arrays. We recruited patients with SLE (n = 211), with other systemic autoimmune diseases (n = 65) and non-autoimmune control subjects (n = 149). Standard clinical and laboratory data were collected and serum complement levels were determined. The genotype of SNP rs1143679 in the ITGAM gene was also determined. Ex vivo formation of immune complexes, with respect to IgM, IgG, complement C4 and C3 binding, was examined using a functional immunoassay on autoantigen microarray comprising nucleic acids, proteins and lipids. Complement consumption of nucleic acids increased upon binding of IgM and IgG even when serum complement levels were decreased due to consumption in SLE patients. A negative correlation between serum complement levels and ex vivo complement deposition on nucleic acid autoantigens is demonstrated. On the contrary, complement deposition on tested protein and lipid autoantigens showed positive correlation with C4 levels. Genetic analysis revealed that the non-synonymous variant rs1143679 in complement receptor type 3 is associated with an increased production of anti-dsDNA IgG antibodies. Notwithstanding, homozygous carriers of the previously reported susceptible allele (AA) had lower levels of dsDNA specific IgM among SLE patients. Both the non-synonymous variant rs1143679 and the high ratio of nucleic acid specific IgG/IgM were associated with multiple organ involvement. In summary, secondary complement deficiency in SLE does not impair opsonization of nucleic-acid-containing autoantigens but does affect other antigens and potentially other complement dependent processes. Dysfunction of the receptor recognizing complement opsonized immune complexes promotes the development of class-switched autoantibodies targeting nucleic acids. | |
Language dc.language | Angol | |
Rent dc.publisher | Public Library of Science (PLoS) | |
Contact information dc.relation.ispartof | urn:issn:1932-6203 | |
Title dc.title | Serological and Genetic Evidence for Altered Complement System Functionality in Systemic Lupus Erythematosus: Findings of the GAPAID Consortium. | |
Type dc.type | folyóiratcikk | |
Date Change dc.date.updated | 2016-04-05T14:23:52Z | |
Language dc.language.rfc3066 | eng | |
Scope dc.format.page | e0150685 | |
Doi ID dc.identifier.doi | doi:10.1371/journal.pone.0150685 | |
MTMT ID dc.identifier.mtmt | 3036334 | |
Issue Number dc.identifier.issue | 3 | |
Journal dc.identifier.jtitle | PLOS ONE | |
Volume Number dc.identifier.volume | 11 | |
Release Date dc.description.issuedate | 2016 | |
Author Details dc.description.author | Prechl, József : 10015636 (ELTE/TTK/Bio_I/MTA-ELTE Immunológiai Kutatócsoport) | |
Author Details dc.description.author | Papp, Krisztián : 10017315 (ELTE/TTK/Bio_I/MTA-ELTE Immunológiai Kutatócsoport) | |
Pubmed ID dc.identifier.pubmed | 26950932 | |
Author institution dc.contributor.department | ELTE/TTK/Bio_I/MTA-ELTE Immunológiai Kutatócsoport | |
Author institution dc.contributor.department | ELTE/TTK/Bio_I/MTA-ELTE Immunológiai Kutatócsoport | |
Author MTMT ID dc.contributor.mtmtid | 10015636 | |
Author MTMT ID dc.contributor.mtmtid | 10017315 | |
Uploader's email dc.description.submitteremail | jprechl@gmail.com | |
Uploader Name dc.description.submittername | Prechl József | |
ID Uploader dc.identifier.submitter | 10015636 |