Check the genetics in your patients with ILD Save

A common misconception is that genetic variants don’t cause disease in adults, says Dr. Korf. According to Dr. Bogunovic, 1 in 4 adults will have a first manifestation of genetic error of immunity in adulthood. Genetics seems to be playing an increasingly huge role in autoimmune diseases, and certainly in ILD, and we are only now starting to recognize it. 

So when should we think about genetics? When you have someone with immune dysregulation, oftentimes with immune deficiencies, strange cytopenias, ILD, things that don’t necessarily add up. Sounds like most of our diseases? Indeed. 

Since I am mostly interested in autoimmune ILD, the messages about genetic testing resonated deeply with me. It seems that many STAT activating mutations and interferenopathies could cause ILD. Add to that variants in telomere maintenance and surfactant related protein genes, and there you have it – ILD and immune dysregulation. By the way, I am convinced that interstitial pneumonia with autoimmune features has an increased prevalence of potentially pathogenic monogenic variants. Immune dysregulation sounds an awful lot like some of the monogenic gain of function or loss of function mutations that we discussed in session by Drs. Bogunovic and Cooper. I have already started checking for common ILD monogenic variants in many of my patients in ILD in my practice. However, perhaps it has not been enough. 

Dr. Bogunovic says, “send the biggest test you can get.” Many of the conventional panels may miss variants in COPA, PI3Kbeta, and other less commonly recognized genes, and you will be left wondering whether a patient truly does not have a genetic component to their disease. Why may it be important to diagnose a monogenic variant in ILD? It allows for anticipatory guidance, cascade testing of relatives, provides closure to patients who may be searching for answers, and most importantly, it may lead to change in therapy. For example, loss of CTLA4 checkpoint may be successfully treated with abatacept. 

These arguments alone make me want to check genetics more. Of note, genetic testing has been getting increasingly more inexpensive in the past few years. If it will help replace all the rest of the diagnostic work-up we might end up doing because of lack of clear diagnosis, the cost-benefit comparison starts weighing heavily towards testing. 

In summary, genetic variants may cause trouble in adults, even for the first time, genetic information can change prognosis and management, and send the biggest test you have to get the most genetic information. with ILD and especially with features that don’t add up into their diagnosis or do not respond to therapy.