An array of possibilities for the study of autoimmunity

Fathman, C. Garrison; Soares, Luis; Chan, Steven M.; Utz, Paul J.

doi:10.1038/nature03726

Cited by 92 publications

(52 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Among the currently available techniques, the combination of proteomics with serology (immunoproteomics (30 -34)) is largely being used to screen for panels of biomarkers and therapeutic targets in patients with infectious diseases (including SC (27,31,35,36)), cancer, or autoimmune disorders (32,(37)(38)(39)(40)(41). This discipline permits characterization of the immunome of a (micro)organism, defined as the subset of the proteome of a (micro)organism that acts as a target for the immune system (42).…”

Section: Not Only Does Systemic Candidiasis (Sc)mentioning

confidence: 99%

Decoding Serological Response to Candida Cell Wall Immunome into Novel Diagnostic, Prognostic, and Therapeutic Candidates for Systemic Candidiasis by Proteomic and Bioinformatic Analyses

Pitarch

Jiménez

Nombela

et al. 2006

Molecular & Cellular Proteomics

130

123

View full text Add to dashboard Cite

In an effort to bring novel diagnostic and prognostic biomarkers or even potential targets for vaccine design for systemic candidiasis (SC) into the open, a systematic proteomic approach coupled with bioinformatic analysis was used to decode the serological response to Candida wall immunome in SC patients. Serum levels of IgG antibodies against Candida wall-associated proteins (proteins secreted from protoplasts in active wall regeneration, separated by two-dimensional gel electrophoresis, and identified by mass spectrometry) were measured in 45 SC patients, 57 non-SC patients, and 61 healthy subjects by Western blotting. Two-way hierarchical clustering and principal component analysis of their serum anti-Candida wall antibody expression patterns discriminated SC patients from controls and highlighted the heterogeneity of their expression profiles. Multivariate logistic regression models demonstrated that high levels of antibodies against glucan 1,3-␤-glucosidase (Bgl2p) and the antiwall phosphoglycerate kinase antibody seropositivity were the only independent predictors of SC. Receiver operating characteristic curve analysis revealed no difference between their combined evaluation and measurement of anti-Bgl2p antibodies alone. In a logistic regression model adjusted for known prognostic factors for mortality, SC patients with high anti-Bgl2p antibody levels or a positive anti-wall enolase antibody status, which correlated with each other, had a reduced 2-month risk of death. After controlling for each other, only the seropositivity for anti-wall enolase antibodies was an independent predictor of a lower risk of fatality, supporting that these mediated the protective effect. No association between serum anti-cytoplasmic enolase antibody levels and outcomes was established, suggesting a specific mechanism of enolase processing during wall biogenesis. We conclude that serum anti-Bgl2p antibodies are a novel accurate diagnostic biomarker for SC and that, at high levels,

show abstract

Section: Not Only Does Systemic Candidiasis (Sc)mentioning

confidence: 99%

Decoding Serological Response to Candida Cell Wall Immunome into Novel Diagnostic, Prognostic, and Therapeutic Candidates for Systemic Candidiasis by Proteomic and Bioinformatic Analyses

Pitarch

Jiménez

Nombela

et al. 2006

Molecular & Cellular Proteomics

130

123

View full text Add to dashboard Cite

show abstract

“…Several proteins can be generated from a single gene, depending on how the genetic information is read (transcribed) and how the resultant protein is modified after translation (posttranslational modification) (72). Analysis of mRNA expression alone therefore is insufficient to determine whether the proteins encoded are really synthesized.…”

Section: Proteomicsmentioning

confidence: 99%

How Can We Measure Immunologic Tolerance in Humans?

Najafian

Albin²,

Newell³

2006

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Prevention and treatment of allograft rejection in organ transplant recipients relies primarily on non-antigen-specific immunosuppression, with all its associated potential hazards and costs. Currently, the status of the recipient immune response is measured by monitoring pharmacologic drug levels and clinical/pathologic evaluation of graft function. Development of reliable assays that can measure accurately the status of the immune response not only would help clinicians customize the prescription of immunosuppressive drugs in individual patients but also may allow their complete withdrawal in some patients with immunologic tolerance. Furthermore, these assays would facilitate the safe evaluation of novel tolerogenic regimens. Achieving this goal has proved to be very difficult because it requires both a more in-depth understanding of complex mechanisms of tolerance and also identification of transplant patients with acquired tolerance to an allograft that can be studied. This review discusses the current understanding of tolerance mechanisms and outlines the unique and specific challenges in development of tolerance/monitoring assays in the field of transplantation. In addition, several of the most promising candidate assays are discussed in detail.

show abstract

“…Array technology has been successfully used to assess autoAb responses in several autoimmune diseases, including systemic lupus erythematous, polymyositis, rheumatoid arthritis, and multiple sclerosis (23)(24)(25). In the present study, we used protein array technology to experimentally examine the scope and specificity of autoAbs in PV.…”

mentioning

confidence: 99%

Multiplexed autoantigen microarrays identify HLA as a key driver of anti-desmoglein and -non-desmoglein reactivities in pemphigus

Sajda

Hazelton

Patel

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Patients with pemphigus vulgaris (PV) harbor antibodies reactive against self-antigens expressed at the surface of keratinocytes, primarily desmoglein (Dsg) 3 and, to a lesser extent, Dsg1. Conventionally, only antibodies targeting these molecules have been thought to contribute to disease pathogenesis. This notion has been challenged by a growing pool of evidence that suggests that antibodies toward additional targets may play a role in disease. The aims of this study were to (i) establish high-throughput protein microarray technology as a method to investigate traditional and putative autoantibodies (autoAbs) in PV and (ii) use multiplexed protein array technology to define the scope and specificity of the autoAb response in PV. Our analysis demonstrated significant IgG reactivity in patients with PV toward the muscarinic acetylcholine receptor subtypes 3, 4, and 5 as well as thyroid peroxidase. Furthermore, we found that healthy first-and second-degree relatives of patients with PV express autoAbs toward desmoglein and non-Dsg targets. Our analysis also identified genetic elements, particularly HLA, as key drivers of autoAb expression. Finally, we show that patients with PV exhibit significantly reduced IgM reactivity toward disease-associated antigens relative to controls. The use of protein microarrays to profile the autoAb response in PV advanced the current understanding of disease and provided insight into the complex relationship between genetics and disease development.pemphigus | autoantibody | protein microarray P emphigus vulgaris (PV) is a blistering autoimmune skin disease characterized by the presence of autoantibodies (autoAbs) directed against keratinocyte surface antigens (1, 2). Although early immunofluorescence studies demonstrated the presence of autoAbs in patient sera that bound to the surface of keratinocytes, a direct role of autoAbs in disease pathogenesis was not established until purified patient IgG (PVIgG) was shown to elicit blister formation upon passive transfer in mice (3). The main targets of these autoAbs were identified as Desmoglein (Dsg) 3 and 1, cadherin proteins that constitute key components of desmosomes, protein complexes responsible for maintaining cell-cell adhesion (4-7). Later experiments in which patient sera depleted of anti-Dsg3 Abs failed to produce blisters when passively transferred to mice (8) seemingly cemented the notion that these autoAbs alone were responsible for blister formation. As a result, subsequent research in the field has focused primarily on autoAbs directed against Dsgs.The assertion that anti-Dsg autoAbs alone are pathogenic was first challenged when PVIgG, lacking any anti-Dsg1 autoAbs, produced blisters when passively transferred into Dsg3-null mice (9). Additionally, several studies have shown that anti-Dsg Ab titers do not necessarily correlate with disease activity, and a subset of patients with PV do not harbor any detectable anti-Dsg Abs (10-14). The presence of pathogenic autoAbs directed against non-Dsg targets could account for th...

show abstract

An array of possibilities for the study of autoimmunity

Cited by 92 publications

References 59 publications

Decoding Serological Response to Candida Cell Wall Immunome into Novel Diagnostic, Prognostic, and Therapeutic Candidates for Systemic Candidiasis by Proteomic and Bioinformatic Analyses

Decoding Serological Response to Candida Cell Wall Immunome into Novel Diagnostic, Prognostic, and Therapeutic Candidates for Systemic Candidiasis by Proteomic and Bioinformatic Analyses

How Can We Measure Immunologic Tolerance in Humans?

Multiplexed autoantigen microarrays identify HLA as a key driver of anti-desmoglein and -non-desmoglein reactivities in pemphigus

Contact Info

Product

Resources

About