Immunoserological parameters in SLE: high-avidity anti-dsDNA detected by ELISA are the most closely associated with the disease activity

Andrejević, Sladjana; Jeremić, Ivica; Sefik-Bukilica, M.; Nikolić, Miloš; Stojimirovic, Biljana; Bonaci-Nikolic, Branka

doi:10.1007/s10067-013-2330-3

Cited by 44 publications

(35 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The dissociation constants obtained for mAbs in this study are similar to previously reported values for target ligands [33] [34] [28]. SPR has been used to detect and study the binding interactions of dsDNA-specific antibodies in patients with SLE [35] while a recent study of ninety-nine patients showed the avidity of dsDNA antibodies correlates with disease activity of lupus nephritis [36]. It is therefore reasonable to assume that the characteristics of the HLA antibodies we describe here relate to their pathogenicity and are therefore likely to be of clinical relevance.…”

Section: Discussionsupporting

confidence: 85%

Direct quantitative measurement of the kinetics of HLA-specific antibody interactions with isolated HLA proteins

et al. 2018

View full text Add to dashboard Cite

HLA specific antibodies vary in their pathogenicity and this is likely to be the net effect of constant chain usage, quantity, specificity, and affinity. Here we have measured the affinity of human monoclonal antibodies for a range of HLA proteins. Purified antibodies and ligands allowed dynamic interactions to be measured directly by surface plasmon resonance. Physiochemical differences between pairs of ligands were quantified using electrostatic mismatch and hydrophobic mismatch scores. All antibodies were characterized by fast on-rates and slow off rates but with a wide range of association rates (k 3.63-24.25 × 10 per mol per second) and dissociation rates (k, 0.99-10.93 × 10 per second). Dissociation constants (K) ranged from 5.9 × 10 M to 3.0 × 10 M. SN320G6 has approximately a twenty-fold greater affinity for HLA A2 compared with SN607D8, but has a similar affinity for HLA-A2 and B57. In contrast, SN607D8 has greater than a twofold greater affinity for HLA-A2 compared with A68. Similarly, WK1D12 has about a threefold greater affinity for HLA-B27 compared with B7. The higher affinity interactions correlate with the specificity of stimulating antigen. This is the first study to directly measure the binding kinetics and affinity constants for human alloantibodies against HLA.

show abstract

Section: Discussionsupporting

confidence: 85%

Direct quantitative measurement of the kinetics of HLA-specific antibody interactions with isolated HLA proteins

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Data indicate that Tscm cells from SLE patients differentiate into effector CD4+ T cells upon stimulation. The level of autoantibody production in SLE is strongly associated with disease activity and Tfh cells help B cells to form germinal centers, leading to production of high‐affinity and isotype‐switched antibodies . Thus, we examined whether Tscm cells from SLE patients could differentiate into Tfh cells.…”

Section: Resultsmentioning

confidence: 99%

Role of Stem Cell–Like Memory T Cells in Systemic Lupus Erythematosus

Lee

Park

Kwon

et al. 2018

Arthritis & Rheumatology

View full text Add to dashboard Cite

Objective Stem cell–like memory T (Tscm) cells are long‐lived memory T cells that have multipotent capacity to differentiate into different subsets. However, the role of Tscm cells in autoimmune diseases remains unclear. Here, we performed phenotypic studies to identify Tscm cells in patients experiencing systemic lupus erythematosus (SLE). Methods CD4+ and CD8+ Tscm cells were identified in SLE patients and healthy controls (HCs). In in vitro culture systems, CD4+ Tscm cells were induced to differentiate into subsets of T cells, including follicular helper T (Tfh) cells, and cytokine production patterns were assessed after stimulation. After confirming induction of transcription factors for Tfh cells, the capacity of CD4+ Tscm‐derived Tfh cells to help B cells was analyzed by measuring antibody secretion. Results The percentages of CD4+ and CD8+ Tscm cells among the naive CD4+/CD8+ or total CD4+ T cell populations were significantly higher in SLE patients than in HCs. Stimulated Tscm cells from SLE patients could replenish themselves and differentiate into other T lymphocyte subsets, including Tfh cells upon stimulation with T cell receptor. Production of T cell factor 1, which is an inducer of Tfh, was also increased. The differentiated Tfh cells increased antibody production by autologous B cells. Conclusion Taken together, these findings suggest that Tscm cells play a role in the pathogenesis of SLE by maintaining Tfh cells.

show abstract

“…Our results confirm that anti-dsDNA IgM is negatively associated with kidney involvement [ 27 ]: SLE patients in the lowest 10-percentile group had higher odds of renal disease. While high avidity dsDNA specific IgG is thought to play a role in SLE pathogenesis and shows association with disease activity [ 28 ] in our hands only kidney and joint involvement was mildly associated with anti-dsDNA IgG levels. Though the presence of the ITGAM susceptibility allele was associated with increased frequency of kidney involvement, in fact the increase affected not single kidney but rather combined involvement of the kidney ( Fig 5 ).…”

Section: Discussionmentioning

confidence: 53%

Serological and Genetic Evidence for Altered Complement System Functionality in Systemic Lupus Erythematosus: Findings of the GAPAID Consortium

Prechl

Papp

Hérincs³

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

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.

show abstract

Immunoserological parameters in SLE: high-avidity anti-dsDNA detected by ELISA are the most closely associated with the disease activity

Cited by 44 publications

References 37 publications

Direct quantitative measurement of the kinetics of HLA-specific antibody interactions with isolated HLA proteins

Direct quantitative measurement of the kinetics of HLA-specific antibody interactions with isolated HLA proteins

Role of Stem Cell–Like Memory T Cells in Systemic Lupus Erythematosus

Serological and Genetic Evidence for Altered Complement System Functionality in Systemic Lupus Erythematosus: Findings of the GAPAID Consortium

Contact Info

Product

Resources

About