Unaffected first-degree relatives of patients with rheumatoid arthritis have an increased number of known risk factors for RA, compared with unaffected controls. However, the prevalence of risk factors in relatives does not equal that seen in patients, according to Dr. Lotta Ljung, senior consultant rheumatologist at Umeå (Sweden) University Hospital.
For example, the unaffected relatives had a significantly greater prevalence of anti–CCP (cyclic citrullinated peptide) protein IgG, IgA, and IgM antibody isotypes and rheumatoid factors of IgM and IgA isotypes than did the controls, Dr. Ljung said at the annual European Congress of Rheumatology, noting that she was not involved in the research. She gave the presentation for researcher Lisbeth Ärlestig, Ph.D., a student at Umeå (Sweden) University, the scheduled presenter who was unable to attend.
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A study has found that first-degree relatives of people with rheumatoid arthritis can have detectable amounts of autoantibodies, but may lack some risk factors or possibly have yet-unidentified protective factors that allow them to remain healthy.
The findings could lead to better understanding of the factors that affect rheumatoid arthritis (RA) development. Because the etiology of RA is still unknown and autoantibodies are common in patients affected with RA (and the anti-CCP antibodies discussed appear to be involved in the pathogenesis of the disease), it is of interest to analyze the prevalence, concentrations, and pattern of antibodies in first-degree relatives in multicase families, according to Dr. Ljung. The lead author was Dr. Solbritt Rantapää Dahlqvist, also of Umeå University.
The investigators set out to evaluate serologic risk markers for the development of RA in relation to genetic and environmental risk factors. They compared serologic findings in RA patients, unaffected relatives, and healthy controls.
The researchers found that in 196 individuals with RA and 156 first-degree relatives from 61 multicase families compared with healthy controls, respectively, the median concentrations of the anti-CCP isotypes were 237.0 AU/mL and 2.1 AU/mL vs. 1.5 AU/mL for IgG anti-CCP; 3.4 AU/mL and 1.0 AU/mL vs. 0.6 AU/mL for IgA anti-CCP; and 53 AU/mL and 28.5 AU/mL vs. 18.5 AU/mL for IgM anti-CCP. The median concentrations of rheumatoid factors were 134.5 mcg/mL and 5.2 mcg/mL vs. 3.3 mcg/mL for IgM RF and 8.3 mcg/mL and 1.4 mcg/mL vs. 1.0 mcg/mL for IgA RF.
The investigators also found that RA patients were significantly more often SE (shared-epitope) positive than were unaffected relatives (73.1% vs. 53.6%; P less than .001), but had similar rates of carriage of the PTPN22t variant (47.7% vs. 45.4%). Both patients and relatives had the variant at higher rates than did controls. Thus, it appears that SE is more important for the development of RA than is the PTPN22t variant, they said.
"The environmental factor of smoking was also more common among the patients and is shown to be an important risk factor" in univariate but not multivariate analysis, they noted.
Indeed, 58% of patients, compared with 46% of relatives, were smokers. Also, IgG and IgA anti-CCP were significantly associated with SE in the patients, but not in the relatives.
Overall, the RA patients had more risk factors for RA than did the relatives (median, four vs. three; P less than .001). The vast majority of RA patients (93%) had at least three risk factors, whereas only about half (53%) of the relatives had at least three risk factors. Risk factors were defined as anti-CCP antibodies, RF, SE, PTPN22t variant, smoking, and age.
The findings show that first-degree relatives can have detectable amounts of autoantibodies, but may lack some other risk factors (such as SE or smoking) and still remain healthy. Another possibility is that they have particular as-yet-unidentified protective factors, the investigators said, adding that a follow-up study would be useful to help determine which of the isotypes provides the most information about disease progression and would thus be most important to analyze to help identify relatives likely to be affected by RA.
The investigators said they had no relevant financial disclosures.