The Immunopathology of Rheumatoid Arthritis and Leishmania donovani Infection in Sudan

Abstract: Immune complexes (IC) and antibody production against self-antigens play a pathological key role in the development of autoimmunity that occurs in patients with parasitic infections and rheumatic diseases. My studies have targeted two groups of patients from Sudan; patients with visceral leishmaniasis (VL) and patients with rheumatoid arthritis (RA).In VL patients I studied the functional role of IC and IC-induced cytokine production in the pathogenesis of the disease and their effect on kidney functions. For the Sudanese RA cohort, I performed a comparative study with Swedish RA patients. I also investigated the Sudanese RA cohort for the occurrence of RA-associated autoantibodies (rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA)) and the diagnostic and prognostic impact of these autoantibodies on the clinical outcome.In the VL project, I demonstrated that Sudanese VL patients had elevated serum levels of IC and of IC-induced cytokine levels in vitro. GM-CSF levels were increased in acute VL patients and in VL patients with ongoing sodium stibogluconate treatment, and the only cytokine that correlated to a high degree with circulating IC levels. Cystatin C was shown to be a superior marker of glomerular function as compared to serum creatinine in VL patients. For the RA project, a comparative study was performed in collaboration with the rheumatology unit at Gävle hospital. We concluded that the clinical picture of RA in Sudan was more severe, with more widespread joint involvement and stronger laboratory signs of inflammation when compared to the Swedish RA patients.ACPA and RF are both included in the new 2010 RA classification criteria. In many RA studies over the world the occurrence of ACPA and RF varies considerably, this may be due to both geographical differences and lack of standardization for RF and anti-CCP in the RA criteria. But in this study we aligned all antibodies to the same diagnostic specificity compared to Sudanese healthy controls. When doing so we determined that IgA RF had the highest diagnostic sensitivity, a finding that differs from Caucasian studies in which IgM RF predominates. IgG RF was also the autoantibody most strongly associated with early age of disease onset and hand deformities, a clinical picture that differs in most Caucasian studies in which ACPA are the strongest markers for bad prognosis. Thus data from this Sudanese RA cohort implies significant clinical and immunological differences compared to Caucasian RA patients.