HLA complement markers in Italian narcoleptic patients with special emphasis on BfF subtyping

Area of Science:

• Immunogenetics
• Neurology
• Human Leukocyte Antigen (HLA) Polymorphisms

Background:

• Narcolepsy is a complex sleep disorder with suspected genetic underpinnings.
• Previous studies indicated a strong association between narcolepsy and specific HLA phenotypes, particularly in Caucasian populations.

Purpose of the Study:

• To investigate human leukocyte antigen (HLA) polymorphisms in narcoleptic patients of Mediterranean origin.
• To explore potential genetic heterogeneity within the narcolepsy patient cohort.
• To examine the association of specific HLA phenotypes and complotypes with narcolepsy.

Main Methods:

• Human leukocyte antigen (HLA) typing was performed on 30 narcoleptic patients, with a focus on Mediterranean individuals.
• Analysis included HLA class I and class III polymorphisms, as well as complotyping (Bf, C4A, C4B).
• Isoelectric focusing was used to detect specific subtypes, such as the Fb subtype.

Main Results:

• A significant association was observed between narcolepsy and the DR2, DQW2 HLA phenotype in the studied cohort (p < 0.0001).
• The complotype BfS, C4A3, C4B1 was also characteristic of these patients.
• A single patient of Black origin exhibited a distinct HLA profile (DR3,5; DQW2,W3; C4A4,4; C4B1,2), challenging the sole involvement of the DR2, DQW1 phenotype.

Conclusions:

• The DR2, DQW2 phenotype and specific complotypes are strongly associated with narcolepsy, even in Mediterranean populations.
• The distinct genetic profile of the Black patient suggests that narcolepsy's genetic etiology may involve multiple HLA associations or other genetic factors.
• No significant genetic heterogeneity was identified based on clinical features within this cohort.