Press release

Discovery of a gene variant that confers risk of multiple sclerosis and lupus


The study, supported by the Italian Multiple Sclerosis Foundation (FISM) and the National Institute on Aging of the NIH, was carried out by an international team of researchers led by Francesco Cucca, M.D., Director of the Institute of Genetic and Biomedical Research of the Italian National Research Council and professor of Medical Genetics at the University of Sassari.

MS and Lupus are autoiummune diseases, caused by the immune system’s attack on a patient’s own normal tissues: the myelin coating of nerves in MS, and the skin, kidneys, and other organs in Lupus.  The mechanism revealed in the study can help to optimize individual therapy for these diseases, depending on the genetic profiles of patients, and can also aid in the development of new therapies.

Spanning a period of 6 years, the research is based on the full sequencing of the genome of thousands of patients and healthy controls, combined with extensive characterization of the immune system in the same individuals.

 The analyses were first done in the population in the Mediterranean island of Sardinia and were extended to cases and controls from mainland Italy, Spain, Portugal, the United Kingdom, and Sweden.  The main discovery is the correlation between the occurrence of a particular sequence variant of the gene TNFSF13B and the development of the autoimmune diseases. 

The protein product of the TNFSF13B gene is the B-cell activating factor, “BAFF”, required for the survival and proliferation of B cells, which in turn make the immune system antibodies. The study revealed that while the synthesis of wild-type (WT) BAFF is regulated by cellular factors that inhibit its over-production, the specific variant “BAFF-var” is refractory to this inhibition. The resulting increase in soluble (s) BAFF, synthesized from BAFF-var, led to correspondingly higher numbers of B cells, elevated antibody production, and augmented risk of autoimmunity.

“This study, is part of our efforts to use genetics as a powerful tool to systematically dissect the biology of autoimmunity and highlight appropriate therapeutic targets” comments Dr. Cucca.

Indeed, these findings validate BAFF as a therapeutic target in autoimmunity and are consistent with the therapeutic efficacy of a monoclonal antibody that neutralizes BAFF, Belimumab, the first targeted therapy for Lupus to show efficacy in a randomized clinical trial.  The results are also in agreement with recent positive results in clinical trials aiming to treat MS and other autoimmune diseases by lowering the numbers of B cells.

“BAFF-var is especially common in Sardinia, facilitating its discovery with a systematic survey of the whole genome, but was also frequent enough in Southern Europe to replicate its effect on autoimmune risk”, added Dr. Maristella Steri, first author of the publication.   “


Francesco Cucca, MD, director of the IRGB CNR. Email:,; Phone: +39 0706754591

Overexpression of the cytokine BAFF and autoimmunity risk,  Maristella Steri, Valeria Orrù, Maria Laura Idda, Francesco Cucca, et al., New England Journal of Medicine,  April 27, 2017 DOI: 10.1056/NEJMoa1610528

Per informazioni:
Francesco Cucca
Irgb - Cnr

Ufficio stampa:
Cecilia Migali
Ufficio stampa Cnr

Capo ufficio stampa:
Marco Ferrazzoli
06 4993 3383
skype marco.ferrazzoli1