I am not as excited about gene variants, per se, as predictive markers in SLE. However, analyses of protein expression levels are promising. Gene variants are of interest, but they do not tell the whole story. All of us inherit all kinds of things that may or may not affect lupus risk. For example, I may have a gene variant (eg, a gene that has to do with the type I interferon receptor). And let us say that I have a particular variant that puts me more at risk for SLE. Downstream from that receptor, the signaling in my immune system may play out very differently from that of another individual with the same genetic start-up (ie, the same receptor variant) because of all of the interactions between all of the proteins in the pathway. Additionally, some of the things that make me, as an individual with SLE, different from another person are not related to lupus risk genes at all (ie, I may have individual variability in the normal immune system function that I have inherited).

Nonetheless, the expression of gene variants implicated in SLE can lead to the underexpression or overexpression of specific proteins, which, in turn, can be measured and might help to guide treatment decisions. For example, a patient with SLE may also have an increased expression of an interferon response gene signature, and this might be an independent risk factor for future disease flares. 

Considering the question of who may be at risk for lupus nephritis, the tools that we have right now are largely clinical. If I have an African American or an Asian patient with antibodies to double-stranded DNA and low complement, I will test that patient for lupus nephritis. That does not mean that you cannot get lupus nephritis in the absence of those factors—because you can—but these clinical variables allow us to have a higher index of suspicion. Once we identify relevant gene expression patterns, we can better identify those patients who are at increased risk for developing lupus nephritis and other complications. I do believe that we are getting closer and closer to figuring out changes in the gene expression patterns that make us worry about lupus nephritis.