A case of anti-IgLON5 disease presenting with unusual clinical features has expanded current understanding of this rare autoimmune disorder. The case was investigated in a collaborative study between Euroimmun and clinics in Lübeck and Hamburg (Germany) and published in the Journal of Neurology.
What is anti-IgLON5 disease?
Anti-IgLON5 disease is a rare and poorly understood neurological disease characterised by autoantibodies against IgLON5, a neuronal cell adhesion molecule. IgLON5 is predominantly expressed in the cerebellum and testes and is thought to play a role in central nervous system development and regulation.
Clinically, patients most commonly present with sleep disorders, bulbar syndrome, gait instability, cognitive impairment and movement disorders. Prognosis is generally poor, although some patients may benefit from immunotherapy.
Case description
The current study describes a patient with anti-IgLON5 disease resistant to first-line therapy. Diagnosis was established by detecting anti-IgLON5 antibodies in serum and cerebrospinal fluid (CSF) using a cell-based indirect immunofluorescence assay (Euroimmun). Initially, the patient presented with sleep apnoea, limb tremor, cerebral haemorrhage, epileptic seizures, psychiatric symptoms, multiple ischemic strokes and kidney failure. As the disease progressed, he developed dysphagia and respiratory failure requiring tracheotomy, accompanied by a persistently reduced level of wakefulness.
First-line treatment with corticosteroids and intravenous immunoglobulins resulted in only transient improvement, followed by further clinical deterioration. Treatment was therefore escalated to second-line immunotherapy with rituximab. Six weeks after initiation, the patient began to show clinical improvement, which continued steadily over the following six months.
Expanding the clinical spectrum
This case is notable for the co-existence of both typical and atypical symptoms of anti-IgLON5 disease. Sleep apnoea and psychiatric features were consistent with the established clinical spectrum and guided the diagnostic investigation. However, the combination of high serum anti-IgLON5 titers with ischemic strokes, cerebral haemorrhage and systemic complications such as renal failure suggest a potentially broader pathophysiological mechanism. The authors propose that microvascular inflammation may contribute to these manifestations. Moreover, the patient’s marked response to rituximab — a B-cell depleting therapy — supports the involvement of B lymphocytes in disease etiopathology.
Anti-IgLON5 as a potential prognostic biomarker
Detection of anti-IgLON5 antibodies in serum strongly supports the diagnosis of anti-IgLON5 disease, and approximately 90% of patients also test positive in CSF. However, the dynamics of antibody titers during treatment have not been well characterised. In this case, clinical improvement was accompanied by a sustained decline in antibody levels. The serum titer decreased from 1:3200 to 1:1000 following repeated intravenous immunoglobulin therapy and further declined to 1:32 six months after the first rituximab dose.
This observation raises the possibility that anti-IgLON5 antibody titers could serve as a prognostic biomarker. Further studies will aim to clarify the role of serum and CSF biomarkers in disease monitoring and better define the immunopathological mechanisms underlying anti-IgLON5 disease.
Learn more about our research at www.neuro-company.com
