BecA-ILRI Hub capacity building program: Empowering African scientists and institutions to solve Africa’s agricultural challenges

<p>Bars show medians, *p<0.05, **p<0.01 Dunn's tests vs. controls. # p<0.05 two-tails, Mann-Whitney -test vs. controls.</p

Increased Immune Complexes of Hypocretin Autoantibodies in Narcolepsy

International audienceBACKGROUND: Hypocretin peptides participate in the regulation of sleep-wake cycle while deficiency in hypocretin signaling and loss of hypocretin neurons are causative for narcolepsy-cataplexy. However, the mechanism responsible for alteration of the hypocretin system in narcolepsy-cataplexy and its relevance to other central hypersomnias remain unknown. Here we studied whether central hypersomnias can be associated with autoantibodies reacting with hypocretin-1 peptide present as immune complexes. METHODOLOGY: Serum levels of free and dissociated (total) autoantibodies reacting with hypocretin-1 peptide were measured by enzyme-linked immunosorbent assay and analyzed with regard to clinical parameters in 82 subjects with narcolepsy-cataplexy, narcolepsy without cataplexy or idiopathic hypersomnia and were compared to 25 healthy controls. PRINCIPAL FINDINGS: Serum levels of total but not free IgG autoantibodies against hypocretin-1 were increased in narcolepsy-cataplexy. Increased levels of complexed IgG autoantibodies against hypocretin-1 were found in all patients groups with a further increase in narcolepsy-cataplexy. Levels of total IgM hypocretin-1 autoantibodies were also elevated in all groups of patients. Increased levels of anti-idiotypic IgM autoantibodies reacting with hypocretin-1 IgG autoantibodies affinity purified from sera of subjects with narcolepsy-cataplexy were found in all three groups of patients. Disease duration correlated negatively with serum levels of hypocretin-1 IgG and IgM autoantibodies and with anti-idiotypic IgM autoantibodies. CONCLUSION: Central hypersomnias and particularly narcolepsy-cataplexy are characterized by higher serum levels of autoantibodies directed against hypocretin-1 which are present as immune complexes most likely with anti-idiotypic autoantibodies suggesting their relevance to the mechanism of sleep-wake cycle regulation

Serum levels of free (A), total (B) and percentage of immune complexes (C) of IgA autoAbs reactive with hypocretin-1 in subjects with central hypersomnia and controls.

<p>Bars show medians, **p<0.01 Dunn's tests vs. controls. # p<0.05, two-tails, Mann-Whitney-tests vs. controls and #a, p<0.05, one-tail Mann-Whitney test.</p

Clinical and biological characteristics of patients with central hypersomnia including narcolepsy-cataplexy (NC), narcolepsy without cataplexy (NWC) and idiopathic hypersomnia (HI).

<p>Significant differences,</p><p><b>^a</b>NC vs. NWC,</p><p><b>^b</b>NC vs. HI,</p><p><b>^c</b>NWC vs. HI.</p

Serum levels of anti-idiotypic IgM autoAbs reactive with hypocretin-1 IgG autoAbs in subjects with central hypersomnia and controls.

<p>Bars show means, *p<0.05, Tukey's test vs. controls. # p<0.05 and ## p<0.01, Student's t-test, two-tails vs. controls.</p

Western blot detection of a band corresponding to the hypocretin precursor protein (16 KDa) in the rat hypothalamic homogenate.

<p><b>A</b>. Detection using human IgG autoAbs affinity purified for hypocretin-1 peptide from sera of NC patients. <b>B</b>. Detection using commercial rabbit anti-hypocretin-1 antiserum. Columns 1, 2 and 3 correspond to 75, 50 and 25 µg, respectively, of protein amount from the hypothalamic homogenate loaded into the gel. Molecular weight markers (KDa) are shown on the left.</p