Biochemical analysis of the epitope specificities of anti-C1q autoantibodies accompanying human lupus nephritis reveals them as a dynamic population in the course of the disease

Stoyanova, Vishnya; Tchorbadjieva, M.; Deliyska, Boriana; Vasilev, Vasil; Tsacheva, Ivanka

doi:10.1016/j.imlet.2012.08.007

Cited by 12 publications

(14 citation statements)

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“…It is shown that several positively charged viral and bacterial peptides and proteins (Quaratino et al, 1995;Wucherpfennig and Strominger, 1995;Hausmann et al, 1999) can mimic sequentially unrelated positively charged autoantigens of human proteins (e.g. myelin basic protein, proteins of ribonucleoprotein complex Ro/La, C1q) (Routsias and Tzioufas, 2010;Stoyanova et al, 2012;Mameli et al, 2014), and can activate autoreactive T and B cell responses (Vaughan et al, 1995;Wucherpfennig and Strominger, 1995;Sospedra et al, 2005). However, sometimes, just like in the case of nuclear antigens and Hu7ap, cross-reactivity between autoantigens and the inducer of the autoantibodies cannot be detected (Vaughan et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Characterisation of the nucleic acid binding features of the PRRSV 7ap and its ability to induce antinuclear antibodies

Olasz

Jankovics

Bálint

et al. 2017

Acta Veterinaria Hungarica

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A short alternative open reading frame named ORF7a has recently been discovered within the nucleocapsid gene of the porcine reproductive and respiratory syndrome virus (PRRSV) genome. Proteins (7ap) translated from the ORF7a of two divergent strains -a type I and a type II -are able to completely reduce the motility of nucleic acids at relatively high molar charge ratios in gel retardation assays indicating strong dsDNA-and ssRNA-binding capability. Conserved RNAand DNA-binding properties suggest that nucleic acid binding is a functional property of the divergent 7aps, and not an arbitrary consequence of their net positive charge. Sera from Hu7ap-immunised pigs and mice did not react with Hu7ap or Hu7ap-GFP; however, antinuclear antibodies were detected in the sera of the immunised animals, suggesting an ability of Hu7ap to interact with or mimic autoantigenic macromolecules.

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Section: Discussionmentioning

confidence: 99%

Characterisation of the nucleic acid binding features of the PRRSV 7ap and its ability to induce antinuclear antibodies

Olasz

Jankovics

Bálint

et al. 2017

Acta Veterinaria Hungarica

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“…Those were discovered in different analyzed cohorts. [22][23][24][25] The results from the detailed biochemical analysis of the epitope specificities of polyclonal anti-C1q autoantibodies in Bulgarian LN patients showed a quite heterogeneous autoantibodies profile (see Table 1). None of the epitope specificities tested was associated with active LN.…”

Section: Anti-c1q Autoantibodiesmentioning

confidence: 99%

“…The latter suggests that the immunogene (antigen) involved in the initiation of anti-C1q autoantibody formation might be an exogenous molecule (pathogen) with a structural similarity to C1q that may initiate an autoimmune response to it on the base of molecular mimicry and cross-reactivity. 25 In regard to the common isotype of anti-C1q antibodies in a LN patient's sera, autoantibodies from the IgG isotype are predominantly detected, with a higher affinity in comparison to IgM. The high potential valency of the polymeric IgM molecule enhances the recruitment of more MBL and C1q, therefore promoting phagocytosis, 26 associated with lower risk for an autoimmune condition.…”

Section: Anti-c1q Autoantibodiesmentioning

confidence: 99%

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Autoantibodies against complement components in systemic lupus erythematosus – role in the pathogenesis and clinical manifestations

Hristova¹,

Stoyanova

2017

Lupus

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Many complement structures and a number of additional factors, i.e. autoantibodies, receptors, hormones and cytokines, are implicated in the complex pathogenesis of systemic lupus erythematosus. Genetic defects in the complement as well as functional deficiency due to antibodies against its components lead to different pathological conditions, usually clinically presented. Among them hypocomplementemic urticarial vasculitis, different types of glomerulonephritis as dense deposit disease, IgA nephropathy, atypical haemolytic uremic syndrome and lupus nephritis are very common. These antibodies cause conformational changes leading to pathological activation or inhibition of complement with organ damage and/or limited capacity of the immune system to clear immune complexes and apoptotic debris. Finally, we summarize the role of complement antibodies in the pathogenesis of systemic lupus erythematosus and discuss the mechanism of some related clinical conditions such as infections, thyroiditis, thrombosis, acquired von Willebrand disease, etc.

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“…The anti-C1q autoantibodies are known to be polyclonal high affinity IgG molecules, produced in an antigen-driven process [ 13 , 14 , 15 ]. The complex structure of C1q provides two types of functional domains—the N-terminal collagen-like region (CLR) and the C-terminal globular heads ghA, ghB and ghC, associated in a globular domain (gC1q).…”

Section: Introductionmentioning

confidence: 99%

Anti-Idiotype scFv Localizes an Autoepitope in the Globular Domain of C1q

Todorova

Rangelov

Bogoeva

et al. 2021

IJMS

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We addressed the issue of C1q autoantigenicity by studying the structural features of the autoepitopes recognized by the polyclonal anti-C1q antibodies present in Lupus Nephritis (LN) sera. We used six fractions of anti-C1q as antigens and selected anti-idiotypic scFv antibodies from the phage library “Griffin.1”. The monoclonal scFv A1 was the most potent inhibitor of the recognition of C1q and its fragments ghA, ghB and ghC, comprising the globular domain gC1q, by the lupus autoantibodies. It was sequenced and in silico folded by molecular dynamics into a 3D structure. The generated 3D model of A1 elucidated CDR similarity to the apical region of gC1q, thus mapping indirectly for the first time a globular autoepitope of C1q. The VH CDR2 of A1 mimicked the ghA sequence GSEAD suggested as a cross-epitope between anti-DNA and anti-C1q antibodies. Other potential inhibitors of the recognition of C1q by the LN autoantibodies among the selected recombinant antibodies were the monoclonal scFv F6, F9 and A12.

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Biochemical analysis of the epitope specificities of anti-C1q autoantibodies accompanying human lupus nephritis reveals them as a dynamic population in the course of the disease

Cited by 12 publications

References 50 publications

Characterisation of the nucleic acid binding features of the PRRSV 7ap and its ability to induce antinuclear antibodies

Characterisation of the nucleic acid binding features of the PRRSV 7ap and its ability to induce antinuclear antibodies

Autoantibodies against complement components in systemic lupus erythematosus – role in the pathogenesis and clinical manifestations

Anti-Idiotype scFv Localizes an Autoepitope in the Globular Domain of C1q

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