Immunogenetic polymorphisms in Guillain-Barré syndrome

Guillain-Barré syndrome is a rare but potentially severe disease in which the peripheral nerves are affected by the immune system. Signaling from brain to muscles is impaired by the immune attack directed to the peripheral nerves, resulting in muscle weakness ranging from a mild decrease of muscle strength to a complete paralysis. GBS is often preceded by an infection with a bacterium (Campylobacter jejuni, Mycoplasma pneumoniae, or Haemophilus influenzae) or a virus (cytomegalovirus, Epstein- Barr virus). These infections commonly occur in the general population. Our immune system is activated to eradicate these invading pathogens. However, in GBS the immune response is not only directed to the pathogen, but also to the peripheral nerve tissue (cross-reactive immune response). Previous reports showed that the bacterium or virus bears structures on its surface that resemble structures present on the peripheral nerves (molecular mimicry). This molecular mimicry is probably crucial for the induction of anti-ganglioside antibodies. However, the production of these antibodies is also dependent of other factors. This thesis focuses on the contribution of genetic host factors in GBS. Two different approaches were used to assess the contribution of these genetic factors: 1. To identify families in which two or more members are affected. 2. To perform genetic population-based association studies comparing large groups of unrelated GBS patients and healthy controls to assess whether candidate immune response genes are susceptibility factors for conferring GBS or associated with clinical and serological subgroups of GBS.

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