Medical Professional Publications

Sanfilippo Syndrome May Trigger Autoimmunity, Leading to Neurological Impairment

Scientists at Nationwide Children’s are the first to demonstrate that lymphocytes, white blood cells important in immunity, may prime an autoimmune response contributing to the neurological impairment in Sanfilippo syndrome type B.

Mucopolysaccharidosis IIIB (MPS IIIB), also known as Sanfilippo syndrome type B, is a rare, heritable disease in young children that results from defects in a lysosomal enzyme.  These patients are unable to appropriately break down long chains of sugar molecules referred to as glycosaminoglycans, causing the carbohydrate heparan sulfate to accumulate in lysosomes throughout the somatic and central nervous system. Children with MPS IIIB appear normal at birth but later show severely delayed neurological development. They are usually diagnosed with this condition within the first few years of life when they are seen to be slow developing or begin to experience losses in developmental achievements. As there is currently no treatment for MPS IIIB, these children usually die before age 20.

“Our previous studies suggest that a robust immune activation in the brains of MSP IIIB mice may be a critical contributor to the progression of the disease,” said Haiyan Fu, PhD, principal investigator in the Center for Gene Therapy at The Research Institute at Nationwide Children’s Hospital and the study’s lead author.  “Yet, we need to determine the role of immunity-triggered lymphocytes in disease progression.”

Although it is unclear how this relates to abnormal central nervous system immune responses seen in MPS IIIB, abnormal heparan sulfates have been described in several autoimmune diseases.

In their study appearing in the Journal of Neuroinflammation, Dr. Fu and colleagues passively immunized mice by injecting them with lymphocytes either from MSP IIIB or other normal mice.  

They found that the mice receiving MPS IIIB lymphocytes developed a mild paralytic clinical disease and had T cells in their brain and spinal cord; T cells are the center of the immune system's response to infection, injury, and inflammation.  No T cells were detected in the brain or spinal cord of mice receiving injections of normal-mouse lymphocytes.

“These data further support that MPS IIIB primes an autoimmune response which may subsequently provoke or exacerbate MPS IIIB neuropathology, independent of lysosomal storage pathology,” said Dr. Fu. “This is the first study to demonstrate that in MPS IIIB mice, lymphocytes can travel to the central nervous system where they promote neuroinflammation contributing to neurological impairment in this disease.”

Since the neuro-immune reaction seen in these mice does not result from infection or injury, Dr. Fu says this model may be useful in studying novel signaling pathways responsible for CNS-immune activation. Further studying the role of specific T cell subsets in MPS IIIB, added Dr. Fu, may lead to the identification of new biomarkers and therapeutic targets, and advance our understanding of the disease.

Killedar S, Dirosario J, Divers E, Popovich PG, McCarty DM, Fu H. Mucopolysaccharidosis IIIB, a lysosomal storage disease, triggers a pathogenic CNS autoimmune response. J Neuroinflammation. 2010 Jul 16;7:39.

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