IgG abnormality in narcolepsy and idiopathic hypersomnia

Abstract

Background: A close association between narcolepsy and the Human Leukocyte Antigen (HLA)-DQB1*0602 allele suggests the involvement of the immune system, or possibly an autoimmune process. We investigated serum IgG levels in narcolepsy.

Methodology/principal findings: We measured the serum total IgG levels in 159 Japanese narcolepsy-cataplexy patients positive for the HLA-DQB1*0602 allele, 28 idiopathic hypersomnia patients with long sleep time, and 123 healthy controls (the HLA-DQB1*0602 allele present in 45 subjects). The serum levels of each IgG subclass were subsequently measured. The distribution of serum IgG was significantly different among healthy controls negative for the HLA-DQB1*0602 allele (11.66+/-3.55 mg/ml), healthy controls positive for the HLA-DQB1*0602 allele (11.45+/-3.43), narcolepsy patients (9.67+/-3.38), and idiopathic hypersomnia patients (13.81+/-3.80). None of the following clinical variables, age, disease duration, Epworth Sleepiness Scale, smoking habit and BMI at the time of blood sampling, were associated with IgG levels in narcolepsy or idiopathic hypersomnia. Furthermore we found the decrease in IgG1 and IgG2 levels, stable expression of IgG3, and the increase in the proportion of IgG4 in narcolepsy patients with abnormally low IgG levels. The increase in the proportion of IgG4 levels was also found in narcolepsy patients with normal serum total IgG levels. Idiopathic hypersomnia patients showed a different pattern of IgG subclass distribution with high IgG3 and IgG4 level, low IgG2 level, and IgG1/IgG2 imbalance.

Conclusions/significance: Our study is the first to determine IgG abnormalities in narcolepsy and idiopathic hypersomnia by measuring the serum IgG levels in a large number of hypersomnia patients. The observed IgG abnormalities indicate humoral immune alterations in narcolepsy and idiopathic hypersomnia. Different IgG profiles suggest immunological differences between narcolepsy and idiopathic hypersomnia.

Figure 1. Serum total IgG level.

Each dot corresponds to the serum IgG level (mg/ml) in each subject. Dotted lines indicate the normal range. The normal range is set at 5.5–22.0 mg/ml according to the manufacturer's instructions. Horizontal lines and squares indicate the mean ± SD of four groups. Outlined-dots indicate the median of four groups.

Figure 2. Serum IgG1 level.

Each dot corresponds to the serum IgG subclass level (mg/ml) in each subject. Dotted lines indicate the mean ± 2SD of healthy control subjects without DQB1*0602 as normal range. Horizontal lines and squares indicate the mean ± SD of five groups.

Figure 3. Serum IgG2 level.

The definitions of dots, dotted lines, horizontal lines, and squares are provided in the legend for Figure 2.

Figure 4. IgG1/IgG2 ratio.

Dots correspond to the IgG1/IgG2 ratio in each subject. The definitions of dotted lines, horizontal lines, and squares are provided in the legend for Figure 2.

Figure 5. Serum IgG3 level.

Definitions of dots, dotted lines, horizontal lines, and squares are provided in the legend for Figure 2.

Figure 6. Serum IgG4 level.

Definitions of dots, dotted lines, horizontal lines, and squares are provided in the legend for Figure 2.