Chronic Malaria Revealed by a New Fluorescence Pattern on the Antinuclear Autoantibodies Test

Abstract

BackgroundSeveral clinical forms of malaria such as chronic carriage, gestational malaria or hyper-reactive malarial splenomegaly may follow a cryptic evolution with afebrile chronic fatigue sometimes accompanied by anemia and/or splenomegaly. Conventional parasitological tests are often negative or not performed, and severe complications may occur. Extensive explorations of these conditions often include the search for antinuclear autoantibodies (ANA).MethodsWe analysed fluorescence patterns in the ANA test in patients with either chronic cryptic or acute symptomatic malaria, then conducted a one-year prospective study at a single hospital on all available sera drawn for ANA detections. We then identified autoantibodies differentially expressed in malaria patients and in controls using human protein microarray.ResultsWe uncovered and defined a new, malaria-related, nucleo-cytoplasmic ANA pattern displaying the specific association of a nuclear speckled pattern with diffuse cytoplasmic perinuclearly-enhanced fluorescence. In the one-year prospective analysis, 79% of sera displaying this new nucleo-cytoplasmic fluorescence were from patients with malaria. This specific pattern, not seen in other parasitic diseases, allowed a timely reorientation of the diagnosis toward malaria. To assess if the autoantibody immune response was due to autoreactivity or molecular mimicry we isolated 42 autoantigens, targets of malarial autoantibodies. BLAST analysis indicated that 23 of recognized autoantigens were homologous to plasmodial proteins suggesting autoimmune responses directly driven by the plasmodial infection.ConclusionIn patients with malaria in whom parasitological tests have not been performed recognition of this new, malaria-related fluorescence pattern on the ANA test is highly suggestive of the diagnosis and triggers immediate, easy confirmation and adapted therapy.

Serologic features of cohorts with variable genetic risk for systemic lupus erythematosus

“…Malaria exposed individuals harbor anti-nuclear antibodies, some of which cross react with malarial antigens. The ANA pattern in malaria is different from patterns observed in SLE, suggesting fine specificity differences, but anti-DNA antibodies have been reported (Hommel et al 2014 ; Hirako et al 2015 ). That these anti-DNA antibodies are primarily IgM is consistent with reports of high IgM antibodies in response to malarial infection (Pleass et al 2016 ; Czajkowsky et al 2010 ).…”

Systematic Analysis of Direct Antiglobulin Test Results in Post-artesunate Delayed Hemolysis

“…This observation suggests that, despite different DAT results, pathophysiologic mechanisms underlying the hemolytic process may be similar for all included patients and not related to DAT positivity. According to the latter hypothesis, the finding of a positive DAT may be only a nonspecific marker of systemic immune activation [47], triggered by the recent malarial episode, instead of a real determinant of the hemolytic anemia.…”

Splénomégalie palustre hyper-réactive

“…La présence d'autoanticorps a été notée au cours de la SPH : anticorps antithyroïdiens [25], anticorps antinucléaires, anticoagulants circulants lupiques, anticorps anti-␤2GP1, test de Coombs direct positif, ANCA atypiques [55]. .…”

“…Dans le contexte de l'exploration d'une splénomégalie subaiguë ou chronique cet aspect est très évocateur du diagnostic de SPH [55]. …”