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Occurrence of rheumatoid arthritis-associated autoantibodies in Sudanese patients with Leishmania donovani infection
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
Unit of Rheumatology, Alribat University Hospital, Khartoum, Sudan.
Department of Microbiology and Parasitology, Faculty of Medicine, University of Khartoum, Sudan.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Objective

Our aim with this investigation was to evaluate the occurrence of anti-cyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF) and circulating immune complexes (IC) in Sudanese patients infected with Leishmania donovani parasite.

Methods

Serum samples were collected from Leishmania infected patients and healthy Sudanese controls. Sudanese anti-CCP positive RA patients were included as positive controls. Data from all analyses were also compared with Swedish healthy control cohorts. Levels of circulating IC and anti-CCP were measured using ELISA and RF using nephelometry. A control plate with cyclic control peptides containing arginine instead of citrulline was used to evaluate citrulline specific reactivity.

Results

We demonstrate that sera from Leishmania infected patients are often RF positive, have elevated IC levels and that a substantial number exhibit antibody reactivity towards CCP. However, contrary to what was evident the in Sudanese RA sera, the CCP reactivity was not restricted to citrulline but reacted equally well with the arginine control peptide.

Conclusions

Our findings stress the importance to interpret a positive CCP test carefully when evaluated in non-rheumatic conditions.

National Category
Infectious Medicine Immunology in the medical area
Research subject
Clinical Immunology
Identifiers
URN: urn:nbn:se:uu:diva-139528OAI: oai:DiVA.org:uu-139528DiVA: diva2:381559
Available from: 2010-12-28 Created: 2010-12-28 Last updated: 2011-01-27
In thesis
1. Functional Role of Immune Complexes in Rheumatic and Parasitic Diseases
Open this publication in new window or tab >>Functional Role of Immune Complexes in Rheumatic and Parasitic Diseases
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Immune complexes (IC) have key pathological roles in both autoimmune and infectious diseases. In this thesis functional mechanisms behind IC-driven inflammation in rheumatic diseases and tropical infections have been studied, with special focus on the contribution of autoantibodies and cytokine-inducing properties of IC. In the autoimmune disease SLE, increased levels of IC-induced cytokines were associated with both increased classical complement activation and the occurrence of the autoantibodies anti-SSA and anti-SSB, both directed against RNA-associated antigens. In addition, complement activation and anti-SSA synergistically predisposed to higher levels of IC in sera. In the following study it was demonstrated that also other autoantibodies against RNA-associated autoantigens were more enriched than anti-dsDNA in SLE IC.

Sudanese Visceral Leishmaniasis (VL) patients had elevated IC levels, and precipitated IC induced higher levels of GM-CSF, IL10, IL6 and IL1RA than control IC. Levels of IC were especially prominent in severely ill patients receiving antimony treatment, and a parallel association with IC induction of GM-CSF was demonstrated. Leishmania-infected patients were often rheumatoid factor (RF) positive and a substantial number displayed reactivity towards cyclic citrullinated peptide (CCP) antigens. Contrary to what was seen in Sudanese RA sera, the CCP reactivity was not restricted to citrulline but reacted equally well with arginine-containing control peptides. Levels of anti-CCP among VL patients were not due to cross-reactions with, or CCP-reactivity bound to IC.

I have demonstrated that IC are associated with the presence of autoantibodies in both SLE and in Leishmania infection. In SLE, autoantibodies against RNA-associated antigens were more prone to form circulating IC than anti-dsDNA. In Leishmania infection false reactivity against the CCP-autoantigen correlated to IC levels although the IC themselves did not contain such reactivity. In both diseases higher IC levels were associated with a more active disease, and purified IC induced key cytokines in disease pathogeneses.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 68 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 636
National Category
Immunology in the medical area
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-139529 (URN)978-91-554-7981-7 (ISBN)
Public defence
2011-02-17, Rudbecksalen, Dag Hammarskjölds väg 20, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2011-01-27 Created: 2010-12-28 Last updated: 2011-03-11Bibliographically approved

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Åhlin, Erik

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