Departments of Internal Medicine and 1Radiology, 2Laboratory of Haematology and 3Laboratory of Immunology, Brugmann University Hospital, Free University of Brussels (ULB), Brussels, Belgium
Correspondence to:
M. P. Guillaume, Department of Internal Medicine, Brugmann University Hospital, 4 place Van Gehuchten, 1020 Brussels, Belgium. E-mail: marie-paule.guillaume{at}chu-brugmann.be
SIR, Sleeping sickness due to Trypanosoma brucei gambiense is characterized by an insidious course leading to extensive nervous system involvement. Neurological manifestations correlate with progression from meningitis to encephalitis, although the precise pathogenic mechanisms remain unclear [1]. Numerous autoantibodies, such as nuclear antibodies and antibodies against central nervous system (CNS)-specific antigens have been reported in this condition [2]. We describe here a case of sleeping sickness in which we identified antinuclear antibodies, which are usually considered to be very specific for systemic lupus erythematosus (SLE), such as anti-membrane DNA (mDNA), anti-ribosome Po and anti-Ku autoantibodies.
A 31-yr-old Angolan man presented with headache, cognitive impairment and periodic fever, which he had had for 18 months. Physical findings included cervical lymphadenopathies, mild neck stiffness, generalized muscle weakness and hyporeflexia in the lower limbs. Blood analysis showed the following results: immunoglobulin (Ig) M, 1020 mg/dl (normal range <320 mg/dl); C4, 0.052 g/l (normal range >0.1 g/l), circulating immune complexes binding C1q, and rheumatoid factor. Cerebrospinal fluid (CSF) analysis yielded the following results: protein, 1.32 g/l; glucose, 39 mg/dl; and leucocyte count 520/mm3 with 83% lymphocytes. Cultures were negative. Blood and CSF were positive for antinuclear antibodies on HEp 2 (serum dilution 1/320, speckled pattern) directed against single-stranded (ss) DNA (50 U/ml), double-stranded (ds) DNA (24 U/ml), mDNA, SSB, Ku and anti-ribosomal Po autoantibodies, anti-Yo and anti-myelin (IgG and IgM). Brain magnetic resonance imaging (MRI) showed contrast uptake in the leptomeninges, with a hyperintense signal in the periventricular white matter, the basal ganglia and the brainstem (Fig. 1). The patient's clinical condition worsened rapidly, with left hemiparesis, areflexia and coma. At this point, a thick smear of blood and a CSF analysis revealed the presence of T. b. gambiense. A 14-day course of eflornithine was followed by progressive clinical improvement. Autoantibodies to nuclear antigens and anti-neurone-specific antigens disappeared completely within 2 weeks and MRI abnormalities in 8 months.
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Trypanosomiasis is accompanied by polyclonal B-cell activation, with increased production of Ig6 that in-cludes not only specific anti-parasite antibodies but also autoantibodies, such as antinuclear antibodies directed against ssDNA and dsDNA, smooth and striated muscle antibodies, and antibodies against CNS-specific antigens, such as anti-myelin and anti-ganglioside antibodies [2, 6]. It is not well established whether the presence of these autoantibodies is due to an immune response to released DNA or to parasite antigens which cross-react with human neuronal antigens or are secondary to non-specific polyclonal B-cell activation [2, 6]. There is a positive correlation between the severity of CNS involvement and the levels of autoantibodies directed against CNS antigens, whereas autoantibodies directed against dsDNA would not affect the course of the disease [6]. However, the pathogenicity of the antibodies against brain proteins remains to be determined. Anti-ribosomal Po antibodies have been also reported in Chagas disease, due to T. cruzi. They cross-react with membrane proteins of cardiomyocytes, and may play a pathogenic role in the cardiomyopathy [7]. The question of whether a similar mechanism can explain the neurological damage in sleeping sickness needs further study.
In our case, these autoantibodies probably reflect an epiphenomenon of the parasitic disease because they disappeared after a specific anti-parasitic treatment alone. Thus, anti-mDNA, anti-Ku and anti-ribosomal Po protein autoantibodies can be added to the list of autoantibodies that appear in the course of sleeping sickness.
The authors have declared no conflicts of interest.
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