title: Chronic malaria revealed by a new fluorescence pattern on the antinuclear autoantibodies test.
abstract: BACKGROUND
  Several 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).
  
  
  METHODS
  We 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  In 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.
authors.affiliation: Immunology Department - Immune Chemistry and Autoimmunity Laboratory, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France ; Parasitology-Mycology Laboratory, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hommel
authors.affiliation: Parasitology-Mycology Laboratory, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Charuel
authors.affiliation: Tropical Infectious Diseases Department, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie, Paris, France ; INSERM (National Institute of Health and Medical Research) UMR-S 945, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Jaureguiberry
authors.affiliation: INSERM (National Institute of Health and Medical Research) UMR-S 945, Paris, France ; Internal Medicine Department, French National Reference Center for SLE and Antiphospholipid Syndrome AP-HP Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Arnaud
authors.affiliation: Immunology Department - Immune Chemistry and Autoimmunity Laboratory, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France.
authors.forename: Regis
authors.initials: R
authors.lastname: Courtin
authors.affiliation: Parasitology-Mycology Laboratory, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Petra
authors.initials: P
authors.lastname: Kassab
authors.affiliation: Department of Internal Medicine and Septic Orthopaedics, Hôpital Croix Saint-Simon, Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Prendki
authors.affiliation: Immunology Department - Immune Chemistry and Autoimmunity Laboratory, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Paris
authors.affiliation: Parasitology-Mycology Laboratory, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Ghillani-Dalbin
authors.affiliation: Immunology Department - Immune Chemistry and Autoimmunity Laboratory, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France ; INSERM (National Institute of Health and Medical Research) UMR-S 945, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Thellier
authors.affiliation: Tropical Infectious Diseases Department, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Caumes
authors.affiliation: Internal Medicine Department, French National Reference Center for SLE and Antiphospholipid Syndrome AP-HP Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Zahir
authors.initials: Z
authors.lastname: Amoura
authors.affiliation: Immunology Department - Immune Chemistry and Autoimmunity Laboratory, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France ; INSERM (National Institute of Health and Medical Research) UMR-S 945, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Mazier
authors.affiliation: Parasitology-Mycology Laboratory, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Musset
authors.affiliation: Immunology Department - Immune Chemistry and Autoimmunity Laboratory, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France ; INSERM (National Institute of Health and Medical Research) UMR-S 945, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Buffet
authors.affiliation: Parasitology-Mycology Laboratory, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Paris, France ; INSERM (National Institute of Health and Medical Research) UMR-S 945, Paris, France ; Internal Medicine Department, French National Reference Center for SLE and Antiphospholipid Syndrome AP-HP Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Makoto
authors.initials: M
authors.lastname: Miyara
mesh_terms: D000974:Antibodies, Antinuclear / Q000097:blood* / Q000276:immunology; D000953:Antigens, Protozoan / Q000097:blood* / Q000276:immunology; D002467:Cell Nucleus / Q000276:immunology / Q000469:parasitology; D002908:Chronic Disease; D003593:Cytoplasm / Q000276:immunology / Q000469:parasitology; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood* / Q000175:diagnosis* / Q000276:immunology / Q000469:parasitology; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000166:cytology / Q000276:immunology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000276:immunology* / Q000302:isolation & purification; D040081:Protein Array Analysis
chemical_list: D000974:Antibodies, Antinuclear; D000953:Antigens, Protozoan