This is the first in our series of author profiles. Please let me introduce you to Professor Bernard Lauwerys who published the paper “sIL7R concentrations in the serum reflect disease activity in the lupus kidney” which can be found here.
Hi Professor Lauwerys please can you tell us a bit about yourself and how you got started in scientific research?
I got involved in SLE research activities after I met Frédéric Houssiau in Brussels during my training in internal medicine and rheumatology. I did a Ph.D. thesis under his supervision about the role of cytokines in the pathogenesis of the disease. In the early 2000, I had the chance to spend 16 months in the laboratory of E.K. Wakeland at UT Southwestern Medical Center at Dallas, where powerful mouse models of the disease were being developed. Since I am back in Brussels, I share my time between clinical duties and translational research activities, taking advantage of our large recruitment of patients with systemic and inflammatory disorders.
What are the messages we should take from your paper?
Active renal disease in the course of lupus nephritis is suggested when rising serum anti-double stranded DNA titers are observed, together with decreased serum C3 levels and an active urinary sediment. Unfortunately, none of these tests are sensitive and specific enough to confirm that active renal inflammation is ongoing, hence the need for a kidney biopsy (and sometimes repeat kidney biopsies) in the initial workup and follow-up of these patients. In our previous work, we provided evidence that the soluble form of the IL-7Receptor (sIL7R) is produced in peripheral tissues upon inflammatory stimulants. In particular, we found that it is produced in the lupus kidney (and not by lupus PBMC), and that serum levels correlate with renal disease activity. In the present publication, we confirmed these observations in an independent cohort of patients, and found that rising sIL7R serum levels are a strong indication that active renal disease (renal BILAG A) is present or will be present in the next 3 months. The main advantage of the test is that it is an easily measurable serum indicator of inflammatory mechanisms happening in the target organ, in this case the kidney.
And what limitations should we be aware of?
As always, there are false negative and false positive cases. If the test had to be implemented in clinical practice, it would be important to use it in the context of other available tests, in the hands of experienced clinicians. As a matter of fact, we did demonstrate in the paper that combining sIL7R measurements with any of the other tests (anti double stranded DNA titers, serum C3, proteinuria) increase the performance of these tests to detect overtly active renal disease. I was also recently very thrilled to find out that one of the few false positive cases we had, did develop active renal disease shortly after publication of the manuscript.
If you wanted to repeat your study, what would you be looking out for that may have taken you by surprise the first time around?
We did not encounter such surprising result. Our study was already a confirmatory study.
What impact will your study have on the field?
There is a strong medical need for such markers of target organ involvement in SLE. In my view, measuring serum sIL7R concentrations in SLE nephritis patients is useful in order to detect relapsing renal disease early on. By opposition to anti-double stranded DNA antibodies or serum C3, sIL7R is not a marker of systemic disease activity, but is related to local inflammatory events. By opposition to proteinuria, it is not a marker of damage as well as of disease activity, but it only reflects disease activity. I am convinced that kidney biopsies are necessary when active renal disease is suspected in a SLE patient, but using sIL7R measurements might help better identify patients in whom the the procedure is warranted.
What still needs to be done in the field?
In real life situations, patients are not (always !) part of a well-identified cohort of individuals with a well-defined disease. sIL7R is produced in other organs where inflammation is present. We have published data about production of the molecule by rheumatoid arthritis synovial fibroblasts, upon stimulation with TNFalpha or IL1beta, and we are accumulating data about the link between serum sIL7R and disease activity in rheumatoid arthritis. Further development of the concept into a diagnostic tool will require additional tests in the context of a collaborative effort, but we are 100% ready to take this endeavour.
Had you heard of open access before submitting to Lupus Science and Medicine? What are your thoughts on open access?
Open Access is a strong improvement in terms of data visibility. I believe that all public funding agencies should include (and fund !) Open Access publishing in their contracts.
What advice would you offer to anyone starting out in the field?
A good clinimetry is the key to successful translational research activities. This is particularly true in the field of SLE, where clinical assessment of disease activity is a science as such. The samples used in the research need to be obtained from patients with a standardized and prospective clinical evaluation. In my view, this really makes the difference between signal and noise!