Lessons From Transcriptome Analysis  of Autoimmune Diseases

Nagafuchi, Yasuo; Yanaoka, Haruyuki; Fujio, Keishi

doi:10.3389/fimmu.2022.857269

Cited by 3 publications

(1 citation statement)

References 86 publications

(96 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These pathways have been previously shown to contribute to autoimmunity and overlap with those enriched in targets of high-titer IgG autoantibodies. [57,58] In this cross-sectional study, the number of high-titer IgG or IgA autoantibodies was not statistically correlated with differences in disease activity or treatment ( Supplementary Fig. 1 ).…”

Section: Resultsmentioning

confidence: 76%

Integrating circulating T follicular memory cells and autoantibody repertoires for characterization of autoimmune disorders

Harris,

Chamseddine,

Chu

et al. 2024

Preprint

View full text Add to dashboard Cite

Introduction. Autoimmune diseases are heterogeneous and often lack specific or sensitive diagnostic tests. Increased percentages of CD4+CXCR5+PD1+ circulating T follicular helper (cTfh) cells and skewed distributions of cTfh subtypes have been associated with autoimmunity. However, cTfh cell percentages can normalize with immunomodulatory treatment despite persistent disease activity, indicating the need for identifying additional cellular and/or serologic features correlating with autoimmunity. Methods. The cohort included 50 controls and 56 patients with autoimmune cytopenias, gastrointestinal, pulmonary, and/or neurologic autoimmune disease. Flow cytometry was used to measure CD4+CXCR5+ T cell subsets expressing the chemokine receptors CXCR3 and/or CCR6: CXCR3+CCR6- Type 1, CXCR3-CCR6- Type 2, CXCR3+CCR6+ Type 1/17, and CXCR3-CCR6+ Type 17 T cells. IgG and IgA autoantibodies were quantified using a microarray featuring 1616 full-length, conformationally intact protein antigens. The 97.5th percentile in the control cohort defined normal limits for T cell subset percentages and total number (burden) of autoantibodies. Results. This study focused on CD4+CXCR5+ T cells because CXCR5 upregulation occurs after cognate T-B cell interactions characteristic of autoimmune diseases. We refer to these cells as circulating T follicular memory (cTfm) cells to acknowledge the dynamic nature of antigen-experienced CXCR5+ T cells, which encompass early progenitors of cTfh or Tfh cells as well as effector memory T cells that eventually lose CXCR5. Compared to controls, 57.1% of patients had increased CXCR5+CXCR3+CCR6+ cTfm1/17 and 25% had increased CXCR5+CXCR3-CCR6+ cTfm17 cell percentages. Patients had significantly more diverse IgG and IgA autoantibodies than controls and 44.6% had an increased burden of autoantibodies. Unsupervised autoantibody clustering identified three clusters of patients with IgG autoantibody profiles distinct from those of controls, enriched for patients with active autoimmunity and monogenic diseases. An increased percentage of cTfm17 cells was most closely associated with an increased burden of high-titer IgG and IgA autoantibodies. A composite measure integrating increased cTfm1/17, cTfm17, and high-titer IgG and/or IgA autoantibodies had 91.1% sensitivity and 90.9% specificity for identifying patients with autoimmunity. Percentages of cTfm1/17 and cTfm17 percentages and numbers of high-titer autoantibodies in patients receiving immunomodulatory treatment did not differ from those in untreated patients, thus suggesting that measurements of cTfm can complement measurements of other cellular markers affected by treatment. Conclusions. This study highlights two new approaches for assessing autoimmunity: measuring CD4+CXCR5+ cTfm subsets as well as total burden of autoantibodies. Our findings suggest that these approaches are particularly relevant to patients with rare autoimmune disorders for whom target antigens and prognosis are often unknown.

show abstract

Section: Resultsmentioning

confidence: 76%

Integrating circulating T follicular memory cells and autoantibody repertoires for characterization of autoimmune disorders

Harris,

Chamseddine,

Chu

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

A nosology of immune diseases from deep immunophenotyping

McDermott

2024

Nat Rev Rheumatol

View full text Add to dashboard Cite

Advanced methods and novel biomarkers in autoimmune diseases ‑ a review of the recent years progress in systemic lupus erythematosus

Fenton

Pedersen

2023

Front. Med.

View full text Add to dashboard Cite

There are several autoimmune and rheumatic diseases affecting different organs of the human body. Multiple sclerosis (MS) mainly affects brain, rheumatoid arthritis (RA) mainly affects joints, Type 1 diabetes (T1D) mainly affects pancreas, Sjogren’s syndrome (SS) mainly affects salivary glands, while systemic lupus erythematosus (SLE) affects almost every organ of the body. Autoimmune diseases are characterized by production of autoantibodies, activation of immune cells, increased expression of pro-inflammatory cytokines, and activation of type I interferons. Despite improvements in treatments and diagnostic tools, the time it takes for the patients to be diagnosed is too long, and the main treatment for these diseases is still non-specific anti-inflammatory drugs. Thus, there is an urgent need for better biomarkers, as well as tailored, personalized treatment. This review focus on SLE and the organs affected in this disease. We have used the results from various rheumatic and autoimmune diseases and the organs involved with an aim to identify advanced methods and possible biomarkers to be utilized in the diagnosis of SLE, disease monitoring, and response to treatment.

show abstract

Lessons From Transcriptome Analysis of Autoimmune Diseases

Cited by 3 publications

References 86 publications

Integrating circulating T follicular memory cells and autoantibody repertoires for characterization of autoimmune disorders

Integrating circulating T follicular memory cells and autoantibody repertoires for characterization of autoimmune disorders

A nosology of immune diseases from deep immunophenotyping

Advanced methods and novel biomarkers in autoimmune diseases ‑ a review of the recent years progress in systemic lupus erythematosus

Contact Info

Product

Resources

About