Pediatric MS Tied to Autoimmune Disorders in Families

Megan Brooks

August 17, 2021

Rates of autoimmune diseases, including thyroid disorders and multiple sclerosis (MS), are higher among families of patients with pediatric MS compared with unaffected families, new research suggests.

This finding "reinforces the fact that there are probably overlapping genetic risk factors for autoimmunity in general, but the specific autoimmune disease a person gets is based on exposures over time," lead author Benjamin M. Greenberg, MD, Departments of Neurology and Pediatrics, University of Texas Southwestern, Dallas, Texas, told Medscape Medical News.

The study was published online August 5 in Neurology: Neuroimmunology and Neuroinflammation.

Higher Prevalence

The case-control study included 495 children and adolescents (median age, 16 years; 65% female) with MS or clinically isolated syndrome and 709 healthy patients (median age, 15 years; 59% female). All were recruited at 17 clinics that were participating in a study of environmental risk factors for pediatric MS.

In unadjusted analyses, the prevalence of a family history of autoimmune disease was significantly higher among children with MS compared with their healthy peers (68.1% vs 49.5%; P < .001).

Conditions for which prevalances were significantly higher among the case group vs the control group were childhood-onset diabetes (6.3% vs 2.7%; P = .002), adult-onset diabetes (44.6% vs 29.8%; P < .001), thyroid disorders (20.0% vs 13.4%; P = .002), rheumatoid arthritis (15.6% vs 9.25; P < .001), MS in non–first-degree relatives (13.7% vs 4.1%; P < .001), and systemic lupus erythematosus (5.7% vs 3.1%; P = .029).

In adjusted analyses in which first-degree history of MS was excluded, the likelihood of having a family member with autoimmune disease was roughly twofold higher in the case group (odds ratio [OR], 2.27; 95% CI, 1.71 – 3.01; P < .001).

In further adjusted analyses, the likelihood of any family history of MS (in non-first-degree relatives) was fourfold higher among case patients compared with control persons (OR, 4.16; 95% CI, 2.57 – 6.75; P < .001).

In addition, there was greater than threefold increased odds of MS among second-degree relatives of patients with pediatric MS compared with control persons (OR, 3.47; 95% CI, 1.36 – 8.86; P = .009).

The OR was 2.64 (95% CI, 1.43 - 4.89; P = .002) when when analysis was restricted to maternal relatives and 6.37 (95% CI, 2.97 - 13.66; P < .001) when it was restricted to paternal relatives.

"The clinical implications are limited when caring for current patients but profound when developing strategies to prevent autoimmune diseases," Greenberg said.

"Finding at-risk individuals will be the cornerstone of public health efforts to prevent autoimmune disease. This may be achieved through targeted vaccination campaigns, vitamin D supplementation, or avoidance of potential triggers," he added.

"Common Genes"

Commenting on the study for Medscape Medical News, Julie Fiol, RN, associate vice president for healthcare access with the National MS Society, said that although MS is not inherited, "there are many common genes" that have previously been identified that contribute to susceptibility to the development of MS.

"This study offers additional evidence that children who develop MS likely have a higher burden of MS risk genes," said Fiol.

"Finding increased rates of other autoimmune or immune-mediated disorders in the family may indicate shared genetic risk factors. This could help researchers figure out common genes that relate to the body’s loss of immune tolerance to its own tissues and organs," she added.

Fiol noted that because pediatric MS is relatively rare, the National MS Society has been funding a consortium of pediatric MS centers for more than a decade in order to "assemble a critical mass of data" to study this condition and to better understand its cause.

"This study is one of dozens from this group that are shedding light on MS risk factors and optimal care for this population," said Fiol.

"While it is too soon, based on this study, to make MS screening recommendations in families with a history of autoimmune disease, the findings could be helpful for clinicians when making a diagnosis of pediatric-onset MS," she said.

Funding for the research was provided by the National Institute of Neurological Disorders and Stroke and the National Multiple Sclerosis Society. Greenberg and Fiol have reported no relevant financial relationships.

Neurol Neuroimmunol Neuroinflamm. Published online August 5, 2021. Full article

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