Arthritis and Autism – Study Strengthens Genetic Link Between Arthritis and Autism

Father figures: Studying men with autoimmune disease may point to genetic contributions to autism risk in their children.

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Men and women with rheumatoid arthritis are at increased risk of having an autistic child, large study based on medical records from Denmark finds1. By linking the risk to both parents, the new work suggests that autism and arthritis share genetic roots.

Rheumatoid arthritis is a condition in which the immune system attacks the membranes around the joints.

Previous studies have linked this and other immune conditions in pregnant women to the risk of autism in their children. Another new study suggests that the immune environment in the womb influences the severity of autism2.

The rheumatoid arthritis study is the first to link the disease in fathers to autism risk.

If genetic factors play a role, the increased risk of autism would be expected regardless of the parent with rheumatoid arthritis, says study researcher Ane Lilleøre Rom, postdoctoral researcher at Copenhagen University Hospital, Rigshospitalet in Denmark. “If only intrauterine factors are important, we would expect to see an association in children of mothers with rheumatoid arthritis.” Lead researcher Lina Steinrud Mørch was unavailable for comment.

A child’s mother and father often live in similar environments. It is therefore always possible that environmental factors are at play, explains Adam Guastella, professor of psychology at the Brain and Mind Center at the University of Sydney in Australia, who was not involved in this study.

There is a “need for really well-controlled investigations in terms of genetic background to resolve this question,” he says.

Guastella led the other new study, linking maternal immune conditions to the severity of autism in children. His findings are consistent with work showing that immune signaling molecules can cross the placenta and alter a child’s brain development.

Relative risk:

Mørch’s team collected data from national health care and birth registers for nearly 2 million children born from 1977 to 2008 and their parents. Of these children, 13,556 have mothers with rheumatoid arthritis and 6,330 have fathers with the disease. (Rheumatoid arthritis is more common in women than in men.) Some parents had the disease before the child was born; others developed it later.

A total of 8,985 children in the study have autism. Among these children, 81 have a mother with rheumatoid arthritis and 39 have a father with rheumatoid arthritis. Researchers found that women and men with rheumatoid arthritis were about 30% more likely to have an autistic child than parents without the disease. The researchers did not calculate the absolute risk for each scenario.

The results held even when the researchers limited their analysis to parents diagnosed with rheumatoid arthritis after the birth of their child. They appeared on October 9 in the Journal of the American Academy of Child and Adolescent Psychiatry.

The results suggest that the risk of autism due to autoimmune diseases goes beyond the intrauterine environment.

“I was a bit surprised that [the risk of autism] wasn’t a bit more into moms” with rheumatoid arthritis, says Betty Diamond, chief of the Center for Autoimmune and Musculoskeletal Disorders at the Feinstein Institute for Medical Research in Manhasset, New York. “I would have thought that immune activation in moms would also predispose [the children].” Diamond was not involved in the work but did study the link between maternal immune activity and autism.

Less than 10 children in the study were mothers who had rheumatoid arthritis before the children were born. The researchers were therefore unable to study this subgroup.

Allergic reaction:

In their study, Guastella and colleagues analyzed data from 220 autistic children and their families in an autism registry in Western Australia. They found that autistic children born to mothers with allergies or asthma had more severe social deficits than those whose mothers had no immune history. The results were based on scores from a questionnaire for parents called the Social Responsiveness Scale.

The findings suggest that having certain immune conditions during pregnancy increases the severity of autism. They appeared on October 10 in Molecular psychiatry.

But the study cannot separate the effects of immune activity during pregnancy from those of a shared genetic predisposition to autism and asthma or allergy. “The most critical thing we don’t know is how much wheezing or itching they had during their pregnancy,” Diamond says.

The researchers found no link between autoimmune diseases such as rheumatoid arthritis in the mother and the severity of autism in the child. However, the study may have been too small to reveal a link, Guastella says. Only 30 of the mothers have an autoimmune disease, and only 16 of them were diagnosed with autism before their child was born.

The Australian and Danish databases do not contain the data needed to determine the extent to which genetics or environment contribute to the link between autism and immune diseases. Studies that incorporate medical records with genetic testing and measurements of immune activity before, during, and after pregnancy could help fill these gaps.

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