Lupus Patients’ Varying Response to Cyclophosphamide Therapy Linked to Genetic Factors in Study

Researchers found that single-nucleotide polymorphisms (SNPs) at a specific genomic location, the FCGR2B-FCRLA locus, is involved in the response of systemic lupus erythematosus (SLE) and lupus nephritis patients to cyclophosphamide treatment. The research, “Response to Intravenous Cyclophosphamide Treatment for Lupus Nephritis Associated with Polymorphisms in the FCGR2B-FCRLA Locus,” was published in The Journal of Rheumatology.

Cyclophosphamide (CYC) is an immunosuppressant drug used to treat a variety of conditions, including lupus nephritis, a kidney inflammation caused by systemic lupus erythematosus in which patients may develop proteinuria (an abnormal quantity of proteins in the urine and a sign of kidney damage), hematuria (presence of blood in the urine), and decreased renal function. Despite cyclophosphamide being one of the main drug therapies for this condition, response to the treatment varies greatly across individuals.

Researchers used a genome-wide and pharmacogenomics association approach to search for genetic variations associated with the drug’s efficacy. The genome-wide association scan was performed in 109 Korean SLE patients with lupus nephritis, who had received intravenous cyclophosphamide therapy. Renal response to treatment was monitored for six months and patients were divided into three categories: complete responders, partial responders, or non-responders. Genome-wide SNP data of the patients was obtained using Illumina Human 610-Quad BeadChip.

Results indicated that 67 patients demonstrated a partial response and 26 patients had a complete response, meaning that a total of 93 of 109 patients had some type of renal outcome improvement. Researchers found that the Fcγ receptor gene (FCGR) cluster at human chromosome 1q23 presented genetic polymorphisms, previously associated with lupus nephritis susceptibility, that were also associated with the response to CYC treatment for lupus nephritis. A significant correlation with response was found for three specific SNPs (rs6697139, rs10917686, and rs10917688), located between the FCGR2B and FCRLA genes. Researchers found that only non-responders (31 percent) carried the minor alleles in these SNPs.

“This first genome-wide association approach for CYC response yielded a robust profile of genetic associations including large-effect SNP in the FCGR2B-FCRLA locus, which may provide better insights to CYC metabolism and efficacy,” the researchers concluded.