Effect of Neuraminidase and Acidification on Complement-Fixing Properties of Human IgA and IgG

Vaerman, J.-P.; Heremans, J. F.

doi:10.1159/000230093

Cited by 18 publications

(2 citation statements)

References 6 publications

(8 reference statements)

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“…An analysis of the sequences of dominant disease variants reported in the ClinVar database identified about 3,759 pathogenic variants as suitable for targeting by a similar approach. This approach has been recently used successfully to correct a semi-dominant mutation in the myosin VI gene, Myo6, using a mouse mutant the reproduce the human DFNA22 deafness mutation (Vaerman and Heremans, 1968).…”

Section: Gene Silencing In Dominant Forms Of Hearing Disordersmentioning

confidence: 99%

Progress in Gene Editing Tools and Their Potential for Correcting Mutations Underlying Hearing and Vision Loss

Botto

Dalkara²,

El-Amraoui³

2021

Front. Genome Ed.

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Blindness and deafness are the most frequent sensory disorders in humans. Whatever their cause — genetic, environmental, or due to toxic agents, or aging — the deterioration of these senses is often linked to irreversible damage to the light-sensing photoreceptor cells (blindness) and/or the mechanosensitive hair cells (deafness). Efforts are increasingly focused on preventing disease progression by correcting or replacing the blindness and deafness-causal pathogenic alleles. In recent years, gene replacement therapies for rare monogenic disorders of the retina have given positive results, leading to the marketing of the first gene therapy product for a form of childhood hereditary blindness. Promising results, with a partial restoration of auditory function, have also been reported in preclinical models of human deafness. Silencing approaches, including antisense oligonucleotides, adeno-associated virus (AAV)–mediated microRNA delivery, and genome-editing approaches have also been applied to various genetic forms of blindness and deafness The discovery of new DNA- and RNA-based CRISPR/Cas nucleases, and the new generations of base, prime, and RNA editors offers new possibilities for directly repairing point mutations and therapeutically restoring gene function. Thanks to easy access and immune-privilege status of self-contained compartments, the eye and the ear continue to be at the forefront of developing therapies for genetic diseases. Here, we review the ongoing applications and achievements of this new class of emerging therapeutics in the sensory organs of vision and hearing, highlighting the challenges ahead and the solutions to be overcome for their successful therapeutic application in vivo.

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Section: Gene Silencing In Dominant Forms Of Hearing Disordersmentioning

confidence: 99%

Progress in Gene Editing Tools and Their Potential for Correcting Mutations Underlying Hearing and Vision Loss

Botto

Dalkara²,

El-Amraoui³

2021

Front. Genome Ed.

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“…Heat or bisdiazobenzidine (BDB)-aggregated. monoclonal (MC) and polycional (PC), monomeric (m-) and polymeric (p-) IgA did not activate human or guinea-pig C [31,33,34]. Moreover, immune complexes (IC) of mouse MOPC-3I5 IgA with DNP proteins not only were unable to promote C3b formation in guinea pig serum, but also inhibited C consumption by highly substituted DNP-BSA and IgG |29.…”

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confidence: 99%

Rat C3 Conversion by Rat Anti‐2,4, Dinitrophenyl (DNP) Hapten IgA Immune Precipitates

et al. 1987

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Monomeric (m-) and polymeric (p-) anti-DNP monoclonal (MC) rat IgA antibodies (Ab) were tested for precipitation with DNP-bovine serum albumin (DNP-BSA) and C3 conversion in rat serum, with rat MC anti-DNP IgG2b used as reference. At equivalence, p-IgA rapidly precipitated DNP-BSA, with little antigen (Ag) left in the supernatant. In contrast, m-IgA at five-fold higher concentration precipitated Ag very slowly, with less than 50% of Ag precipitated at equivalence. The Ag/Ab weight ratio at equivalence was 0.13 for both m- and p-IgA, but the molar ratio was 0.3 for m-IgA and close to 1.0 for p-IgA, suggesting a higher avidity of p-IgA. Rat C3 conversion by rat IgA immune precipitates (IP) was about 20% with m-IgA and 40% with p-IgA. EGTA did not significantly affect these figures. Therefore, rat MC IgA IP activated the rat alternative C pathway. Neither rat nor mouse IgA anti-DNP IP activated C3 in normal human serum.

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Activation of rat complement by soluble and insoluble rat IgA immune complexes

Rits¹,

Hiemstra

Bazin

et al. 1988

Eur J Immunol

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The ability of rat monoclonal IgA, specific for 2,4-dinitrophenyl (DNA), to activate the complement (C) system of the rat was investigated using aggregated IgA or IgA immune complexes (IC). IgA was coated onto a solid phase, and tested for its capacity to bind C3 upon incubation at 37 degrees C in normal rat serum (NRS) in the presence of Mg-EGTA. Binding of C3 was observed dependent on the dose of dimeric (d-), polymeric (p-) and secretory IgA tested. In contrast, little C3 fixation was observed in this system with monomeric (m-) rat IgA or with mouse m- and d-IgA (MOPC315). Soluble and insoluble rat IgA IC were prepared using dinitrophenylated rat serum albumin (DNP8RSA) as antigen (Ag), and assessed for C activation. It was shown that insoluble IC (immune precipitates; IP) containing m-, d- or pIgA of rat origin activate the alternative pathway of rat C, as demonstrated by their capacity to induce C consumption in NRS in the presence of Mg-EGTA. When p- and m-IgA IP were compared for their capacity to activate C, it was found that p-IgA activated C four times as efficiently as m-IgA IP (at 2 mg/ml). Soluble rat IgA IC were prepared in an excess of DNP8RSA, fractionated by gel filtration on Sepharose 6B, and analyzed for C activation and antibody (Ab)/Ag ratio. In contrast to m-IgA IP, soluble m-IgA did not activate C. On the other hand soluble d-IgA IC activated C dependent on their concentration and size: at a concentration of 0.1 mg/ml high-molecular weight d-IgA IC with a high Ab/Ag ratio were four times as efficient as low-molecular weight IC with a low Ab/Ag ratio, and twice as efficient as IP prepared at equivalence. To demonstrate the induction by IgA of the assembly of the terminal membrane attack complex, trinitrophenyl (TNP)-conjugated rat red blood cells (TNP-RRBC) coated with d- or p-IgA were shown to be lysed in NRS in the presence of Mg-EGTA. No lysis of m-IgA-coated TNP-RRBC was observed. The results in this study demonstrate that both soluble and insoluble rat IgA IC activate the alternative pathway of homologous rat C. Alternative pathway activation by soluble rate IgA IC is dependent on the size of the IC. The degree of polymerization of the IgA Ab itself also influences C activation.

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Effect of Neuraminidase and Acidification on Complement-Fixing Properties of Human IgA and IgG

Cited by 18 publications

References 6 publications

Progress in Gene Editing Tools and Their Potential for Correcting Mutations Underlying Hearing and Vision Loss

Progress in Gene Editing Tools and Their Potential for Correcting Mutations Underlying Hearing and Vision Loss

Rat C3 Conversion by Rat Anti‐2,4, Dinitrophenyl (DNP) Hapten IgA Immune Precipitates

Activation of rat complement by soluble and insoluble rat IgA immune complexes

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