Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Occurrence of Rheumatoid Arthritis-Associated Autoantibodies in Leishmania Donovani Infection.

Ahlin1,  Erik, Elshafie2,  Amir, Nur4,  Musa A. M., Safi3,  Sayda Hassan El, Ronnelid1,  Johan

Clinical Immunology Unit, Uppsala University, Uppsala, Sweden
Clinical Immunology Unit, Uppsala University, Uppsala, Sweden. Department of Pathology and Microbiology, Alribat University Hospital, Khartoum, Sudan
Department of Microbiology and Parasitology, Faculty of Medicine, University of Khartoum, Sudan
Unit of Rheumatology, Alribat University Hospital, Khartoum, Sudan

Background:

The presence of antibodies against citrullinated peptides (anti-CCP) and rheumatoid factors (RF) are closely associated with rheumatic diseases but are also seen in a number of infectious diseases. Our aim with this investigation was to evaluate the occurrence of anti-CCP, RF and circulating immune complexes (CIC) in Sudanese patients infected with the Leishmania donovani parasite. The infection causes an internal disease called visceral leishmaniasis (VL) with an immunopathology characterised by a strong humoral immune response with high production of antileishmanial antibodies, CIC, and polyclonal activation of B-lymphocytes, all factors that could give rise to rheumatic-like manifestations.

Methods:

Serum samples were collected from 136 Leishmania infected patients and 85 healthy Sudanese controls. Twenty-one Sudanese anti-CCP positive RA patients diagnosed following the 1987 ACR criteria were also included in the study. Levels of CIC were measured by a solid-phase C1q assay. Anti-CCP was measured using a commercial ELISA-test kit. A control plate with cyclic peptides containing arginine instead of citrulline as the antigen was used to evaluate citrulline specific reactivity. Rheumatoid factor was measured by nephelometry.

Results:

Among both Leishmania-infected patients and anti-CCP positive RA patients the majority (86% in both groups) were RF positive while the frequency of CIC positivity was higher among VL patients (VL: 38%, CCP pos. RA: 24%). When anti-CCP reactivity was analysed, 11% of VL patients were found to be positive. The levels of anti-CCP among VL patients correlated well to the CIC levels found (rho: 0.59, p<0.001). In the RA group no association was found between CIC and anti-CCP. To rule out the possibility that anti-CCP positivity was due to cross reactions with CIC, we adsorbed C1q binding CIC from sera and evaluated CCP reactivity afterwards. This procedure did not diminish the anti-CCP reactivity in either the VL group or among anti-CCP positive RA patients. We then went on to analyse the citrulline specificity among anti-CCP positive patients. All anti-CCP-positive VL patients showed equivalent reactivity towards CCP and the non citrullinated control peptide. This was in strict contrast to the anti-CCP positive Sudanese RA patients among whom anti-CCP was restricted to CCP (p<0.0001).

Conclusions:

In this study we found that sera from Leishmania infected patients were often RF positive, had elevated CIC levels and that a substantial amount showed reactivity towards CCP. However, contrary to what was seen in RA sera, the CCP reactivity was not restricted to citrulline. This argues that this is an effect of extensive inflammation and immune activation more than a sign of shared pathogenic characteristics with anti-CCP positive arthritis. Furthermore, our findings stress the importance to interpret a positive CCP test carefully.

To cite this abstract, please use the following information:
Ahlin, Erik, Elshafie, Amir, Nur, Musa A. M., Safi, Sayda Hassan El, Ronnelid, Johan; Occurrence of Rheumatoid Arthritis-Associated Autoantibodies in Leishmania Donovani Infection. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :695
DOI: 10.1002/art.28463

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