The role of humoral autoimmunity in the aetiology of achalasia.

Achalasia is rare motility disorder of the oesophagus and characterised by
aperistalsis of the oesophageal body and dysrelaxation of the lower oesophagus
sphincter (LOS) caused by progressive destruction and degeneration of the
neurons in the myenteric plexus. The pathogenesis of the disease is still
largely unknown. Genetic, infectious and neurodegenerative mechanisms have
been suggested as possible aetiological factors. A better understanding of the
aetiological mechanisms of the disease may provide a serological biomarker that
can be used as a diagnostic tool and perhaps will allow us to identify the
disease in an earlier stage before widespread destruction of the neurones has
occured.

A causative role for autoimmune mechanisms in achalasia gained more support in
the recent years due to the association of achalasia with other autoimmune
diseases and histopathology of the oesophagus of patients with achalasia which
showed activated lymphocyte infiltrates within the myenteric plexus.
Furthermore it has been suggested that antimyenteric antibodies play an
important role in this disease because various studies have observed
antineuronal antibodies in the serum of patients with achalasia. None of these
studies however, reported that the antineuronal anitbodies are specific for a
single subtype of the enteric neurones in the myenteric plexus, while it is
suggested that in achalasia especially inhibitory neurones are decreased. This
brings in to question if the antimyenteric antibodies are pathogenic for
achalasia or just an epiphenomenon. Clearly a better understanding of the
actual role of humoral autoimmunity in patients with achalasia is needed.

Primary:
To investigate the presence of disease-specific antimyenteric antibodies and to
identify their target-antigen in patients with achalasia.

Secondary:
- To determine to what extent humoral autoimmunity is the etiological factor in
idiopathic achalasia.
- To investigate whether antineuronal antibodies can be used as a biomarker of
achalasia.
- To find new targets for therapy focused on humoral autoimmunity.
- Collect demographic and clinical data of patients with idiopathic achalasia
and first degree relatives.

A prospective observational study

Patients with achalasia will donate 30mL or 60mL of venous blood, control
patients will donate 30mL. No serious risks are associated with blood
withdrawal. Furthermore participants will be asked to complete a questionnaire
for demographic and clinical data, which isn't associated with any risks. The
results of the study have no consequences for the participants. No financial
compensation will be paid. The study can provide new insights in the
pathogenesis of achalasia and possibly offer new targets for therapy and
diagnosis, which may benefit all patients with achalasia.