Macrophage migration inhibitory factor in nodding syndrome

G. Benedek, M.A. El Latif, K. Miller, M. Rivkin, A.A.R. Lasu, L.P. Riek, R. Lako, S. Edvardson, S. Arbel-Alon, Eithan Galun, M. Levite

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Nodding syndrome (NS) is a catastrophic and enigmatic childhood epilepsy, accompanied by multiple neurological impairments and neuroinflammation. Of all the infectious, environmental and psychological factors associated with NS, the major culprit is Onchocerca Volvulus (Ov)–a parasitic worm transmitted to human by blackflies. NS seems to be an ’Autoimmune Epilepsy’ in light of the recent findings of deleterious autoimmune antibodies to Glutamate receptors and to Leiomodin-I in NS patients. Moreover, we recently found immunogenetic fingerprints in HLA peptide-binding grooves associate with protection or susceptibility to NS. Macrophage migration inhibitory factor (MIF) is an immune-regulatory cytokine playing a central role in modulating innate and adaptive immunity. MIF is also involved in various pathologies: infectious, autoimmune and neurodegenerative diseases, epilepsy and others. Herein, two functional polymorphisms in the MIF gene, a −794 CATT5– 8 microsatellite repeat and a −173 G/C single-nucleotide polymorphism, were assessed in 49 NS patients and 51 healthy controls from South Sudan. We also measured MIF plasma levels in established NS patients and healthy controls. We discovered that the frequency of the high-expression MIF-173C containing genotype was significantly lower in NS patients compared to healthy controls. Interestingly however, MIF plasma levels were significantly elevated in NS patients than in healthy controls. We further demonstrated that the HLA protective and susceptibility associations are dominant over the MIF association with NS. Our findings suggest that MIF might have a dual role in NS. Genetically controlled high-expres-sion MIF genotype is associated with disease protection. However, elevated MIF in the plasma may contribute to the detrimental autoimmunity, neuroinflammation and epilepsy. © 2021 Benedek et al.
Original languageEnglish
Article numbere0009821
JournalPLoS Neglected Tropical Diseases
Issue number10
StatePublished - 2021

Bibliographical note

Export Date: 09 August 2022; Cited By: 2; Correspondence Address: G. Benedek; Tissue Typing and Immunogenetics Unit, Department of Genetics, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel; email:


  • Adolescent
  • Adult
  • Animals
  • Child
  • Child, Preschool
  • Female
  • Genotype
  • Humans
  • Macrophage Migration-Inhibitory Factors
  • Male
  • Microsatellite Repeats
  • Nodding Syndrome
  • Onchocerca volvulus
  • Polymorphism, Single Nucleotide
  • Young Adult
  • autoantibody
  • cytokine
  • DNA fragment
  • glutamate receptor
  • HLA antibody
  • macrophage migration inhibition factor
  • microsatellite DNA
  • 3' untranslated region
  • adaptive immunity
  • adolescent
  • adult
  • allele
  • Article
  • autoimmunity
  • benign childhood epilepsy
  • blood sampling
  • capillary electrophoresis
  • child
  • cognition
  • cohort analysis
  • controlled study
  • degenerative disease
  • DNA extraction
  • DNA sequencing
  • enzyme linked immunosorbent assay
  • eye examination
  • female
  • fluorescence
  • follow up
  • food intake
  • gene expression
  • gene frequency
  • gene locus
  • genetic polymorphism
  • genetic variation
  • genotype
  • haplotype
  • human
  • innate immunity
  • macrophage migration
  • major clinical study
  • male
  • muscle mass
  • nervous system inflammation
  • nodding syndrome
  • onchocerciasis
  • physical examination
  • polymerase chain reaction
  • preschool child
  • prevalence
  • promoter region
  • psychological aspect
  • restriction site
  • saliva
  • school child
  • single nucleotide polymorphism
  • swallowing
  • tonic clonic seizure
  • animal
  • blood
  • genetics
  • parasitology
  • physiology
  • young adult


Dive into the research topics of 'Macrophage migration inhibitory factor in nodding syndrome'. Together they form a unique fingerprint.

Cite this