Fcγ-receptor gene polymorphisms and the pharmacokinetics of immunoglobulin treatment in the Guillain-Barré syndrome

Immunoglobulins are the first choice treatment for patients with the Guillain-Barré syndrome, an acute and devastating disease of peripheral nerves. Patients with a severe form may become fully paralysed within a day and need ventilator support at an intensive care unit. The clinical recovery after treatment with immunoglobulins highly varies from one patient to another. Some patients unfortunately show very little recovery after a standard dosage of immunoglobulins.

This phenomenon is currently unexplained, but may be related to the rapid breakdown of the medicine by some individuals. Variation between persons in the genes coding for the immunological receptors of immunoglobulins may play an important role. These so-called Fcγ-receptors can both increase and decrease the breakdown of immunoglobulins.

Our hypothesis is that some patients with Guillain-Barré syndrome have a variant of these receptors that causes rapid consumption of the immunoglobulins, so these will have an insufficient therapeutic effect. Probably these patients may benefit from higher dosages of immunoglobulins.

If the current study would show that the Fcγ-receptors influence the therapeutic effect of immunoglobulins, then future genetic testing could help to adjust the optimal dosage of immunoglobulins. It would also help to further understand the mechanisms by which immunoglobulins work in this disease.

Curriculum vitae of Bart C. Jacobs

Dr. Jacobs received his MD and PhD at the Erasmus MC, University Medical Center of Rotterdam, The Netherlands (both cum laude). The topic of his thesis was of the role of infections, molecular mimicry and cross-reactive antibodies in the pathogenesis of Guillain-Barré syndrome (GBS). He and his research group have been working on GBS ever since. They have contributed to the clinical characterisation and diagnosis, epidemiology, immunopathogenesis, pharmacokinetics of immunoglobulin treatment, and prediction of clinical outcome of GBS. Since 2003 he is working at the Departments of Neurology and Immunology of the Erasmus MC as a staff neurologist and immunologist. Dr. Jacobs is the initiator and principle investigator of the International GBS Outcome Study (IGOS), a prospective, observational cohort study on the biological and clinical determinants and predictors of the clinical course of GBS.