## Map all SLE autoantibodies beyond their known targets

Systemic lupus erythematosus (SLE) is defined by a broad and heterogeneous autoantibody response. A positive antinuclear antibody is the obligatory entry criterion for the 2019 EULAR/ACR research classification of SLE.

Aringer et al., *Annals of the Rheumatic Diseases*, 2019.

Clinical and research panels measure a small fraction of that response, and they measure it precisely. Those panels are the right tool for a known target.

The antibody reactome is the full complement of antibody-antigen interactions present in an individual's serum (or plasma) at a given time point. In SLE, the breadth of that reactome remains incompletely characterized. Novel autoantigens linked to disease subsets and severity remain to be identified, along with candidate biomarkers for cohort stratification.

## How MIPSA reads the antibody reactome

Antibody Reactomics is the measurement of all antibody reactivities in a sample. MIPSA (Molecular Indexing of Proteins by Self-Assembly) is the technology that deciphers these reactivities, and HuSIGHT is the human MIPSA antigen library. HuSIGHT represents the full human proteome, roughly 20,000 protein-coding genes, as more than 15,000 full-length proteins and more than 353,000 overlapping 90-amino-acid peptide tiles.

Larman and colleagues, *Nature Biomedical Engineering*, 2022;6(8):992-1003.

## What the screen adds to SLE autoantigen discovery

### Unbiased on two axes

The screen runs the cohort as submitted and reads it against the library as built, with no target list specified in advance. An autoantigen nobody has named yet is in the library already, so it can surface in the result.

### Two antigen formats, two classes of epitope

Full-length proteins are folded, so they present conformational epitopes. The peptide tiles map linear epitopes, including the immunodominant regions inside each target.

### Built-in validation

Recovering known SLE autoantigens in the same run gives the screen its positive controls. An unnamed hit identified as significantly and differentially detected represents a novel candidate autoantigen.

### Robust reproducibility above 0.95

Inter-replicate Pearson correlation is typically above 0.95, so the same sample returns the same reactivities from run to run.

## Known targets recovered, novel autoantigens detected in the same run

Infinity Bio screened SLE and control serum by MIPSA against the HuSIGHT library, then identified antigens significantly enriched in SLE.

The screen recovered known SLE autoantigens, and also detected novel autoantigens enriched in the SLE cohort. The novel hits showed differential reactivity comparable to the known targets.

- Ro60/SSA
- Sm (SNRPB/C/N)
- U1-RNP (SNRP70)
- Ro52/TRIM21
- ribosomal P (RPLP0)

[
![Volcano plot of the SLE antibody reactome screen. Horizontal axis, log2 fold change SLE over control. Vertical axis, negative log10 FDR-adjusted P value, with the significance cutoff drawn at P = 0.05. Known SLE autoantigens are blue, novel hits orange, points elevated in controls black, and points that did not reach significance grey. Labelled markers are RPLP0, TRIM21, SNRPN, RO60, SNRP70, SNRPB and SNRPC; SSB is labelled in grey below the cutoff.](https://cdn.sanity.io/images/vbcbvda6/production/67424f1e4d5d2321c6fb4c383608f63736855ead-1739x1213.png?w=1400&auto=format&q=80)
](https://cdn.sanity.io/images/vbcbvda6/production/67424f1e4d5d2321c6fb4c383608f63736855ead-1739x1213.png)

Click the figure to open it full size

 One screen of SLE and control serum samples against 368,000+ human protein and peptide targets. Known SLE autoantigens and novel autoantigens enriched in SLE both reach significance (FDR-adjusted P <= 0.05) with comparable differential reactivity. SLE n = 15, controls n = 30. x-axis: log2 fold change (SLE / control). y-axis: negative log10 FDR-adjusted P value.
 Source: Infinity Bio internal data. SLE and control serum samples screened by MIPSA against the HuSIGHT library. Novel candidates are unlabeled.

## Inputs and turnaround

SampleSerum, microliter-scale
Archived samplesBanked serum works
Turnaround6 to 8 weeks
LibrariesCombinable in one assay

## Read further

- [The MIPSA method paper](/resources/unbiased-discovery-of-autoantibodies-associated-with-severe-covid-19-via-genome/)

Larman and colleagues, *Nature Biomedical Engineering*, 2022;6(8):992-1003.

## Add Antibody Reactomics to your next discovery cohort.

The next big discovery is sitting in a freezer right now. If a lupus cohort is banked and its autoantibody profile is uncharacterized, one screen can return previously reported specificities and novel candidates together. Your next discovery awaits.

[Scope an SLE pilot](https://infinitybio.com/contact)

For Research Use Only. Not for use in diagnostic procedures.