How Autoimmune & Non-Autoimmune Family Conditions Predict Rheumatoid Arthritis

Predicting who will develop rheumatoid arthritis (RA) is an important first step toward preventing the disease. Beyond a family history of RA, other autoimmune diseases may predispose someone to RA due to overlapping heritability or disease mechanisms. Examples: One study suggested a family history of lupus and connective tissue disease predicts RA.¹ Other research has shown a link between RA and type 1 diabetes, thyroid disease, inflammatory bowel disease and multiple sclerosis.² 

However, this research did not adjust for potential confounders, such as smoking, explains Cynthia Crowson, PhD, a professor of medicine and rheumatology at the Mayo Clinic, Rochester, Minn. She is the co-author of a new study investigating how family history may be connected to predicting the development of RA.³

Dr. Crowson and her co-authors wondered whether family histories of certain autoimmune and non-autoimmune diseases may predict RA diagnosis and how this association may be affected by confounders. To test this hypothesis, they identified 821 cases of RA in the Mayo Clinic Biobank, using a rules-based algorithm that combines two occurrences of RA diagnosis codes and compared the results with the association of 79 comorbidities from family histories that were self-reported on the Biobank’s baseline questionnaire.⁴

Through this investigation, Dr. Crowson and her colleagues aimed to build a deeper understanding of the potential links between RA and a family history of autoimmune and non-autoimmune diseases. They adjusted for six potential confounders: age, sex, body mass index (continuous), race (non-Hispanic white vs. all others), education (bachelor’s degree or higher vs. all others) and smoking status (ever vs. never).

Key Findings
Although a family history of RA was the most significant predictor for developing RA, study subjects with a family history of other autoimmune diseases, such as lupus, thyroid disease, inflammatory bowel disease and celiac disease also showed a strong association with the risk for RA. The family histories of some non-autoimmune diseases, such as pulmonary fibrosis, obstructive sleep apnea, liver disease and autism, also showed an association with an increased risk for RA. In contrast, a family history of type 2 diabetes and Parkinson’s disease trended toward a decreased risk for RA.

Such findings have not been reported previously, Dr. Crowson says. “This information may provide new insights into how RA develops, [because] there may be genes or environmental exposures shared within a family that are common to both RA and one or more of these diseases. For example, smoking is an environmental exposure that is linked to both pulmonary fibrosis and RA, and smoke exposure is often shared within a family.”

Better RA Care
The family histories the research found to be associated with an increased risk for RA “should increase suspicion of RA when providers are considering a diagnosis of RA,” Dr. Crowson says. She believes the family histories associated with an increased risk for RA could be used to refine tools to predict who is going to develop RA.

“These family histories along with other factors, such as the presence of rheumatoid factor or cyclic citrullinated peptide antibodies, should be used to identify people at risk for developing RA who may benefit from additional screening for RA or preventive strategies,” Dr. Crowson says. “Early initiation of disease-modifying antirheumatic drugs can prevent irreversible joint damage and improve the long-term health outcomes of people with RA.”

Carina Stanton is a freelance science journalist based in Denver.

References

1. Frisell T, Hellgren K, Alfredsson L, et al. Familial aggregation of arthritis-related diseases in seropositive and seronegative rheumatoid arthritis: A register-based case-control study in Sweden. Ann Rheum Dis. 2016 Jan;75(1):183–189.
2. Kuo CF, Grainge MJ, Valdes AM, et al. Familial aggregation of rheumatoid arthritis and co-aggregation of autoimmune diseases in affected families: A nationwide population-based study. Rheumatology (Oxford). 2017 Jun 1;56(6):928–933.
3. Kronzer VL, Crowson CS, Sparks JA, et al. Family history of rheumatologic, autoimmune and non-autoimmune diseases and risk of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2019 Nov 30. [Epub ahead of print].
4. Chung CP, Rohan P, Krishnaswami S, et al. A systematic review of validated methods for identifying patients with rheumatoid arthritis using administrative or claims data. Vaccine. 2013 Dec 30;31 Suppl 10:K41–K61.