Genetic cause of lupus found

A new Yale study may lead to a cure for lupus.

Researchers at the Yale School of Medicine identified a genetic mutation that causes lupus, an autoimmune disease without a known cure. The gene typically repairs errors in DNA sequences, and the researchers observed symptoms of lupus in mice when the gene became mutated. While the finding opens new avenues of research, the study — published in Cell Reports on Jan. 16 — did not name the precise mechanism linking the mutation to the disease.

“For a long time people thought that mutations in DNA repair genes could be linked to lupus, and this is actually one of the first demonstrations that a mutation in a DNA repair gene is actually linked to lupus,” said Joann Sweasy, study senior author and professor of therapeutic radiology and genetics at the Yale School of Medicine.

The researchers did not set out to investigate the genetics of lupus — instead, they first tried to identify how a DNA repair mechanism distinguishes between correct and incorrect DNA bases. To answer this question, the research team mutated the DNA repair gene POLB in mice, thinking that the mice would exhibit symptoms of cancer.

But instead cancer, the researchers began to see symptoms of lupus. Most conspicuously, they noticed that the mice had elevated levels of antinuclear antibodies, a classic marker of lupus. According to Sweasy, the reason for this elevation might be that the mutated POLB gene was creating antibodies that attacked the animals’ own cells, leading to lupus.

The finding holds promise for helping physicians diagnose lupus and researchers develop treatments, said Alireza Senejani, study lead author and a research scientist in therapeutic radiology at the Yale School of Medicine.

“I think that the contribution to the science community is going to be high because [lupus] is a very complex disease and there is a lot to be learned,” he said. “What we found in this study was how important DNA pathways are.”

According to Betty Diamond, head of the Center of Autoimmune and Musculoskeletal Diseases at the Feinstein Institute for Medical Research in New York who was not involved with the study, nanotechnology may hold the key to locating the source of the antinuclear antibodies the study researchers observed. Pinpointing the origin of the antibodies will enable researchers to develop minimally toxic treatments, she said.

But for Eric Meffre, a professor of immunobiology at the Yale School of Medicine, the correlational nature of the study leaves much in question.

“I think that one of the major questions that remains to be addressed is that despite some of the observations that are recorded in this manuscript, it really does not explain why the mice developed lupus,” he said.

According to the Lupus Research Institute, the disease currently affects more than 1.5 million Americans.

Comments