Problems & Chances in Autoimmunity Biomarker Discovery

The Immunity Fingerprint

The immune sys­tem is far from a stat­ic, pre-determ­ined range of responses. As we go through our lives, the envir­on­ment sculpts immunity, driv­ing the body to pro­duce bil­lions of anti­gen-spe­cif­ic anti­bod­ies. What is more, a baseline of autoantibod­ies exists in all humans – and the sta­bil­ity and react­iv­ity of this fin­ger­print determ­ine a wide range of dis­eases, from autoim­mune con­di­tions to can­cer and dia­betes.

A Growing Concern or an Opportunity?

Autoim­munity is on the rise. Not only are we see­ing an increase in autoim­mune dis­ease occur­rence, but we’re under­stand­ing the inflam­mat­ory aspect of high-mor­bid­ity and mor­tal­ity con­di­tions like heart dis­ease and malig­nan­cies. The rel­ev­ance of anti­body research spans way bey­ond autoim­mune dis­ease. Thus, the steady increase of autoim­munity patients that walks through clin­ic doors is both a con­cern and an oppor­tun­ity:

  • From a physician´s per­spect­ive, we need bet­ter tools for dia­gnos­is (espe­cially early iden­ti­fic­a­tion) and effi­cient, tar­geted treat­ment options.
  • On the research side, we have an improved under­stand­ing of autoim­munity as an under­ly­ing mech­an­ism for a vari­ety of con­di­tions. This means we can focus our efforts on study­ing autoantibod­ies as a way to cre­ate these bet­ter dia­gnost­ic and treat­ment options.

The bot­tom line? We need accur­ate bio­mark­ers – soon­er rather than later. But how can we find them? Here is what you need to know:

The Search for Biomarkers

The tra­di­tion­al approach to bio­mark­er dis­cov­ery goes some­thing like this:

  • Patients walk in with a set of symp­toms, iden­ti­fied as a cer­tain dis­order.
  • You look at the cause of dis­ease and search for a con­di­tion-spe­cif­ic bio­lo­gic­al pro­cess.
  • Then form a hypo­thes­is about the suit­able bio­mark­ers and test it using stand­ard meth­ods such as ELISA and West­ern Blot.

While this meth­od provides very clear data, it is a bot­tom-up approach that may not work for autoim­mune dis­eases. In con­di­tions like SLE, where the cause is unclear, test­ing sep­ar­ate mark­ers through clas­sic meth­ods is deadly expens­ive. But the cost isn´t even the most chal­len­ging aspect. Hypo­thes­is-based mod­els are highly biased because they rely on a pre­vi­ous under­stand­ing of the dis­ease. Since our under­stand­ing of autoim­munity is only just devel­op­ing, can you really trust that you´ll “stumble” on the bio­mark­er with this approach? For­tu­nately, there is a bet­ter way:

Are Protein Arrays Your Supertool?

On the oppos­ite end of anti­body-based bio­mark­er dis­cov­ery are large-scale meth­ods such as pro­tein arrays. This is a top-down meth­od where you can start with symp­to­mat­o­logy alone, identi­fy indi­vidu­al autoantibody pro­files, and enjoy a high chance of dis­cov­ery in a single exper­i­ment. Our pro­tein arrays use a mem­brane with spot­ted E.coli clones, express­ing a wide range of human anti­gens. From full-length pro­tein to frag­ments and neoanti­gens, you can look at over 10,000 inter­ac­tions with a single run.

Why is this so excit­ing for autoim­munity research?

  • Autoantibod­ies exist against a large por­tion of the human pro­teo­me.
  • Sys­tem­ic dis­eases like SLE (and most oth­er autoim­mune con­di­tions) affect vir­tu­ally all sys­tems.
  • The cause-to-dis­ease path­way of these con­di­tions is poorly under­stood, mak­ing biased meth­ods a less effi­cient way of bio­mark­er dis­cov­ery.

In short, since autoim­munity involves such a wide range of tar­gets, it makes sense to look into as many poten­tial bio­mark­ers as pos­sible. Pro­tein arrays allow you to stream­line dis­cov­ery in a cost and labour-effect­ive way. What is more, you can use subar­rays to nar­row down your bio­mark­er study even fur­ther. The pro­cess looks like this:

  • Run your exper­i­ment using our hEXse­lect or Uni­PEx array, which test for thou­sands of anti­gens.
  • Use the res­ults to select poten­tial anti­gens.
  • We will cre­ate subar­rays, based on your selec­tion.
  • Use the subar­rays to run even more samples, enjoy­ing the even lower time and money costs of your exper­i­ment.

Our Case Study for Systemic Lupus Erythematosus (SLE

Sys­tem­ic Lupus Eryth­em­atosus (SLE) is a chron­ic inflam­mat­ory con­di­tion, the most com­mon and ser­i­ous type of lupus. Immune dys­reg­u­la­tion res­ults in autoantibody and immune com­plex form­a­tion, lead­ing to tis­sue dam­age across sys­tems. We know the autoim­mune attack causes inflam­ma­tion and con­trib­utes to SLE death causes. How­ever, the cause of SLE remains unknown.

With a dis­ease like this, where autoim­munity affects everything, how do we find some­thing to latch on for bio­mark­er dis­cov­ery?

In a recent exper­i­ment our sci­ent­ists ran, we ana­lysed SLE patient sera, along with self-declared healthy donors. Using a pro­tein array work­flow, we got fast res­ults with high data out­put. With our pro­tein arrays, you can enjoy this high dis­cov­ery power even with few­er sample sera (<50 µl), too.

What did we find out?

We presen­ted the res­ults at the 12th Autoim­munity Con­gress. If you missed out, you can still watch the present­a­tion and down­load the poster: But, there is a lar­ger con­clu­sion than can be drawn from the setup.

The Takeaway

Autoim­munity is a com­plex, often poorly under­stood top­ic that can offer new per­spect­ives toward rheum­at­oid dis­eases and oth­er con­di­tions. With multisys­tem dis­orders, bio­mark­er dis­cov­ery can be a chal­lenge, because of the sheer range of pro­teo­me-tar­geted anti­bod­ies to be tested.

Our pro­tein arrays allow you to check over 10,000 anti­gens in a single run – and with a smal­ler sample size. If you have SLE sera lay­ing around, this is a great oppor­tun­ity to identi­fy poten­tial bio­mark­ers through a bias-free meth­od.

Fol­low­ing this unbiased start to dis­cov­ery, you can then design a detailed study to find the bio­mark­er you are look­ing for. Fol­low-up exper­i­ments com­par­ing anti­body sub­classes as well as dis­ease vari­ants and treat­ment path­ways lead to a paper-ready res­ult with the poten­tial to change patients’ lives.

Ready to eval­u­ate the poten­tial for your pro­ject? Get a free brain­storm­ing ses­sion!


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