Specific autoantibodies of SLE, such as anti-Ku, anti-ribosome Po and anti-membrane DNA autoantibodies, in a case of human African trypanosomiasis

M.-P. Guillaume, N. Hermanus1, A. Demulder2, G. Servais3 and R. Karmali

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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FIG. 1. Axial MRI. Extensive white and grey matter lesions with mild left cerebral mass effect.

 
The originality of this report resides in the detection for the first time of autoantibodies (anti-Ku and anti-ribosomal Po protein) that have been considered hitherto as very specific to SLE, especially if found in the CSF, and mDNA autoantibodies that have been reported as a new, highly specific marker for SLE [35].

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.

References

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  2. Kazyumba G, Berney M, Brighouse G, Cruchaud A, Lambert PH. Expression of the B cell repertoire and autoantibodies in human African trypanosomiasis. Clin Exp Immunol 1986;65:10–8.[ISI][Medline]
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  4. Agius MA, Chan JW, Chung S, Lee E-K. Role of antiribosomal P protein antibodies in the diagnosis of lupus isolated to the central nervous system. Arch Neurol 1997;54:862–4.[Abstract]
  5. Servais G, Guillaume MP, Dumarey N, Duchateau J. Evidence of autoantibodies to cell membrane associated DNA: a new specific marker for rapid identification of SLE. Ann Rheum Dis 1998;57:606–13.[Abstract/Free Full Text]
  6. Hunter CA, Jennings FW, Tierney JF, Murray M, Kennedy PGE. Correlation of autoantibody titres with central nervous system pathology in experimental African trypanosomiasis. J Neuroimmunol 1992;41:143–8.[CrossRef][ISI][Medline]
  7. Kaplan D, Ferrari I, Bergami PL et al. Antibodies to ribosomal P proteins of Trypanosoma cruzi in Chagas disease possess functional autoreactivity with heart tissue and differ from anti-P autoantibodies in lupus. Proc Natl Acad Sci USA 1997;94:10301–6[Abstract/Free Full Text]
Accepted 31 March 2003





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