BERLIN—Research into factors surrounding prearthritis is uncovering genetic and environmental factors at play at the earliest stages of development of rheumatoid arthritis (RA), giving doctors and patients more hope for earlier interventions, Iain McInnes, PhD, professor of medicine at the University of Glasgow, Scotland, said at the European League Against Rheumatism (EULAR) 2012 Annual European Congress of Rheumatology, held June 6–9.
In a session dedicated to highlighting the latest research in early arthritis and in juvenile disease, Dr. McInnes said he found 23,000 papers in the last year when he searched for the terms “early” and “arthritis.”
“Genome-wide association studies have dominated the literature,” he said.
One retrospective study looking at the genetic studies already done—and comprising 5,000 RA cases and 15,000 controls—found that three proteins at five amino-acid positions account for almost all of the link between the major histocompatibility complex and seropositive RA. They are HLA-DRB1 at positions 11, 71, and 74, HLA-B at position 9, and HLA-DPB1 at position 9.1
Dr. McInnes said the findings mean that we are “closer to understanding what the underlying autoreactive peptides might be.”
He also highlighted studies focusing on environmental factors. A study featuring the sequencing of the microbiome of the mouth in new-onset, never-treated RA patients found that advanced forms of periodontal disease are prevalent in RA and that Porphyromonas gingivalis exposure was similar in RA and controls. Perhaps most interesting, the researchers found that Prevotella and Leptotrichia were the only species in early RA that do not appear to be associated with periodontal disease—a finding that calls for more study.2
Another study found that the number of pack years smoked, together with a single- or double-shared epitope, “exponentially increases the odds ratio of developing rheumatoid arthritis,” clearly showing a gene and environment interaction, Dr. McInnes said.3
One study found that lung abnormalities, including thickening of the bronchial walls, was more common in anticitrullinated protein autoantibody (ACPA)–positive patients than in subjects who were ACPA negative. The abnormalities were also elevated in those with early arthritis compared to controls.4
Dr. McInnes also highlighted two studies in epigenetics, including one that looked at microRNA 146, which is suppressed by smoking. In miR146 knockout mice, autoimmunity arose, with the mice developing an enlarged spleen and lymph nodes.5
“This is an exciting clue that there might now be a link between smoking and immune function and arthritis development,” he said.
Another study found, conversely, that a miR155 deficiency in mice led to a reduction in collagen-induced arthritis.6
