Serum autoantibodies in childhood opsoclonus-myoclonus syndrome: An analysis of antigenic targets in neural tissues

doi:10.1016/S0022-3476(97)70272-5

The Journal of Pediatrics

Volume 130, Issue 6, June 1997, Pages 878-884

https://doi.org/10.1016/S0022-3476(97)70272-5 Get rights and content

Abstract

Objective: Opsoclonus-myoclonus (OM) is a rare neurologic syndrome affecting children and adults. In children it occurs as a parainfectious process or a paraneoplastic syndrome in association with neuroblastoma. Evidence for an immune mechanism includes the presence of serum autoantibodies to several neural antigens and improvement of symptoms with immunosuppressive therapy. We studied the neural antigenic targets of serum IgM and IgG autoantibodies from nine children with OM.

Design: We studied sera from nine children with OM, three with associated neuroblastoma and six with a prodromal viral illness. Control subjects (n = 77) included four children with neuroblastoma but not OM, 32 children with other neurologic disorders, and 41 with nonneurologic illnesses. We studied the neural antigenic targets of serum IgM and IgG autoantibodies by the following methods: (1) immunostaining of human cerebellar sections and peripheral nerve, and (2) Western blot analysis with human brain fractions including white matter, gray matter, and cerebellar Purkinje cells and nuclei.

Results: Sera from all nine children with OM had IgM and IgG binding to the cytoplasm of cerebellar Purkinje cells and to some axons in white matter. In peripheral nerve, IgM and IgG from all nine OM sera bound to large and small axons. Western blot analysis showed a distinctive pattern of binding to several neural proteins, including a 210 kd antigen identified as the high molecular weight subunit of neurofilament. No control serum showed a similar pattern of reactivity.

Conclusion: Opsoclonus-myoclonus syndrome in childhood is associated with a distinctive pattern of serum IgM and IgG binding to neural tissues and antigens.

Section snippets

Postviral syndrome (patient 2)

A 10-month-old boy had an inner ear infection with subsequent development of irritability, opsoclonus, myoclonus, and mild ataxia. Examination showed random conjugate, dancing-like eye movements. Myoclonus was bilateral and involved the arms more than the legs. Ataxia was both appendicular and truncal. He was unable to stand unassisted. Sensation was intact to light touch and pain. Results of computed tomography of the brain and cerebrospinal fluid examination were normal. No clinical,

Patients and sera

Sera from nine children (3.9 ± 2.4 years at the time of testing) with OM syndrome were studied (Table I).

. Human cerebellar staining with sera from patients with OM and control subjects

Patient No.	Sex	Age at onset of symptoms (yr)	Age at testing (yr)	Neuroblastoma	Stage ²⁸	IgM-positive autoantibodies to neural antigens
1	F	2.2	2.2	−	NA	+
2	M	0.8	0.8	−	NA	+
3	F	1.1	1.1	−	NA	+
4	F	2.1	2.1	−	NA	+
5	M	1.2	2.9	−	NA	+
6	M	0.8	5.2	−	NA	+
7	F	3.0	14.4	+	I	+
8	F	1.2	2.6	+	I	+
9	F	1.6	7.8	+	I	+
10	M	NA	3.4	+	IV	−
11	M	NA	1.3	+	IV	−
12	M	NA	5.6	+	IV	−
13	M	NA	4.6	+	IV	−
32 Neurologic controls		NA	2.7 ± 1.4

IgM

All nine serum samples from the children with OM showed IgM binding to Purkinje cell cytoplasm and to axons in peripheral nerve (Fig. 1) and cerebellar white matter.

. Opsoclonus-myoclonus IgM autoantibodies binding to large and small axons in peripheral nerve. Immunostaining (1:100) with serum from patient 2 demonstrates distinct axonal binding to both large and small fibers (magnification ×875). One month after treatment with corticotropin, immunostaining (1:100) with serum from patient 2

DISCUSSION

IgM autoantibodies from the nine OM sera all demonstrated a similar pattern of binding to neural antigens by both immunocytochemistry and Western blot analysis. Immunohistochemistry showed that IgM and IgG from all nine OM sera stained cerebellar Purkinje cell cytoplasm and axons. Western blot analysis of white matter, gray matter, and cerebellar subfractions showed IgM autoantibodies from all nine OM sera bound to proteins with six different molecular weights. The largest, 210 kd protein,

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Serum autoantibodies in childhood opsoclonus-myoclonus syndrome: An analysis of antigenic targets in neural tissues☆,☆☆

Abstract

Section snippets

Postviral syndrome (patient 2)

Patients and sera

IgM

DISCUSSION

J Neuroimmunol

J Pediatr

J Pediatr

Brain Res

J Neuroimmunol

Pediatr Neurol

Myoclonic encephalopathy of infants

J Neurol Neurosurg Psychiatry

Myoclonic encephalopathy or “dancing eyes syndrome”: report of 7 cases with long term follow-up and review of the literature

Helv Paediatr Acta

The neurobiology of the opsoclonus-myoclonus syndrome

Clin Neuropharmacol

Antibodies to Purkinje cells and peripheral nerve in opsoclonia

Lancet