ABSTRACT
Infectious pathogens contribute to the development of autoimmune disorders, but the mechanisms connecting these processes are incompletely understood. Here we show that Plasmodium DNA induces autoreactive responses against erythrocytes by activating a population of B cells expressing CD11c and the transcription factor T-bet, which become major producers of autoantibodies that promote malarial anaemia. Additionally, we identify parasite DNA-sensing through Toll-like receptor 9 (TLR9) along with inflammatory cytokine receptor IFN-γ receptor (IFN-γR) as essential signals that synergize to promote the development and appearance of these autoreactive T-bet+ B cells. The lack of any of these signals ameliorates malarial anaemia during infection in a mouse model. We also identify both expansion of T-bet+ B cells and production of anti-erythrocyte antibodies in ex vivo cultures of naive human peripheral blood mononuclear cells (PBMC) exposed to P. falciprum infected erythrocyte lysates. We propose that synergistic TLR9/IFN-γR activation of T-bet+ B cells is a mechanism underlying infection-induced autoimmune-like responses.
Subject(s)
Anemia, Hemolytic, Autoimmune/etiology , Anemia, Hemolytic, Autoimmune/immunology , B-Lymphocyte Subsets/immunology , B-Lymphocyte Subsets/parasitology , DNA, Protozoan/immunology , Malaria, Falciparum/complications , Malaria, Falciparum/immunology , Plasmodium falciparum/immunology , Toll-Like Receptor 9/metabolism , Anemia, Hemolytic, Autoimmune/parasitology , Animals , Autoantibodies/biosynthesis , Erythrocytes/immunology , Erythrocytes/parasitology , Female , Humans , Lymphocyte Activation , Malaria, Falciparum/parasitology , Mice , Mice, Inbred C57BL , Mice, Knockout , Plasmodium falciparum/pathogenicity , Receptors, Interferon/deficiency , Receptors, Interferon/genetics , Receptors, Interferon/metabolism , T-Box Domain Proteins/deficiency , T-Box Domain Proteins/genetics , T-Box Domain Proteins/metabolism , Toll-Like Receptor 9/deficiency , Toll-Like Receptor 9/genetics , Interferon gamma ReceptorABSTRACT
Background Babesiosis, a tickborne zoonotic disease caused by intraerythrocytic protozoa of the genus babesia, is characterized by nonimmune hemolytic anemia that resolves with antimicrobial treatment and clearance of parasitemia. The development of warm-antibody autoimmune hemolytic anemia (also known as warm autoimmune hemolytic anemia [WAHA]) in patients with babesiosis has not previously been well described. Methods After the observation of sporadic cases of WAHA that occurred after treatment of patients for babesiosis, we conducted a retrospective cohort study of all the patients with babesiosis who were cared for at our center from January 2009 through June 2016. Data on covariates of interest were extracted from the medical records, including any hematologic complications that occurred within 3 months after the diagnosis and treatment of babesiosis. Results A total of 86 patients received a diagnosis of babesiosis during the 7.5-year study period; 18 of these patients were asplenic. WAHA developed in 6 patients 2 to 4 weeks after the diagnosis of babesiosis, by which time all the patients had had clinical and laboratory responses to antimicrobial treatment of babesiosis, including clearance of Babesia microti parasitemia. All 6 patients were asplenic (P<0.001) and had positive direct antiglobulin tests for IgG and complement component 3; warm autoantibodies were identified in all these patients. No alternative explanation for clinical hemolysis was found. WAHA required immunosuppressive treatment in 4 of the 6 patients. Conclusions We documented post-babesiosis WAHA in patients who did not have a history of autoimmunity; asplenic patients appeared to be particularly at risk.
Subject(s)
Anemia, Hemolytic, Autoimmune/parasitology , Babesia microti , Babesiosis/complications , Splenectomy/adverse effects , Adult , Anemia, Hemolytic, Autoimmune/immunology , Autoantibodies/blood , Babesia microti/immunology , Babesia microti/isolation & purification , Babesiosis/drug therapy , Female , Humans , Male , Risk Factors , Transfusion ReactionABSTRACT
This report details a case of reversible cold agglutinins in a dog with Mycoplasma cynos pneumonia. An 11-month-old female spayed Rhodesian Ridgeback was presented for lethargy and cough. Thoracic radiographs revealed an alveolar pattern present bilaterally in the cranioventral lung lobes. Septic neutrophilic inflammation with suspected Mycoplasma sp. organisms was noted on cytologic examination of a trans-tracheal wash, and the dog was treated empirically with IV ampicillin/sulbactam and enrofloxacin pending culture results. Red blood cell agglutination was noted unexpectedly on several blood film reviews during hospitalization; however, the dog never developed clinical or laboratory evidence of hemolysis. Cold agglutinins were demonstrated based on the results of a saline dilution and cold agglutinin test that showed agglutination at 4°C but not at room temperature (21°C) or 37°C. Based on a positive culture for M cynos, the dog was treated for 8 weeks with oral enrofloxacin. After clinical and radiographic resolution of the pneumonia, repeated saline dilution and cold agglutinin tests of peripheral blood were negative at all temperatures. Reversible, asymptomatic cold agglutinins are common in human patients with mycoplasma pneumonia, but this is the first reported case in a dog.
Subject(s)
Anemia, Hemolytic, Autoimmune/veterinary , Dog Diseases/parasitology , Mycoplasma Infections/veterinary , Mycoplasma/classification , Pneumonia, Bacterial/veterinary , Anemia, Hemolytic, Autoimmune/parasitology , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Dog Diseases/blood , Dog Diseases/drug therapy , Dog Diseases/etiology , Dogs , Enrofloxacin , Fluoroquinolones/administration & dosage , Fluoroquinolones/therapeutic use , Mycoplasma Infections/blood , Mycoplasma Infections/complications , Mycoplasma Infections/drug therapy , Pneumonia, Bacterial/complications , Pneumonia, Bacterial/drug therapy , Pneumonia, Bacterial/microbiologyABSTRACT
A three year old male from the Democratic Republic of the Congo was admitted to Monroe Carell Jr. Children's Hospital at Vanderbilt with a 10-day history of fever, emesis, and diarrhea. Examination demonstrated scleral icterus, splenomegaly, and anemia. By peripheral blood smear, the patient was diagnosed with Plasmodium ovale. Immunohematology demonstrated a positive direct antiglobulin test (DAT) for IgG and C3d with pan-agglutination on eluate. These findings, in combination with hemolytic labs, signified presence of an autoimmune hemolytic anemia (AIHA). We believe this to be the first reported case of P. ovale infection-mediated AIHA.
Subject(s)
Anemia, Hemolytic, Autoimmune/parasitology , Malaria/blood , Plasmodium ovale/isolation & purification , Anemia, Hemolytic, Autoimmune/blood , Anemia, Hemolytic, Autoimmune/diagnosis , Child, Preschool , Humans , MaleABSTRACT
We have recently treated three patients with malaria who developed post malaria immune mediated hemolysis. These cases, seen with in a span of three month period (September 09 to November 09) form the basis of this report. Out of three patients, two were treated with steroids and both responded favorably.
Subject(s)
Anemia, Hemolytic, Autoimmune/diagnosis , Malaria/complications , Malaria/diagnosis , Plasmodium falciparum/isolation & purification , Plasmodium vivax/isolation & purification , Adolescent , Anemia, Hemolytic, Autoimmune/parasitology , Anemia, Hemolytic, Autoimmune/therapy , Antimalarials/adverse effects , Antimalarials/therapeutic use , Blood Transfusion , Child , Erythrocyte Count , Erythrocytes/pathology , Female , Fever/etiology , Glucocorticoids/therapeutic use , Hemolysis , Humans , Malaria/drug therapy , Malaria/parasitology , Prednisolone/therapeutic use , Treatment OutcomeSubject(s)
Anemia, Hemolytic, Autoimmune/parasitology , Coccidiosis/veterinary , Hepatitis, Animal/immunology , Hepatitis, Animal/parasitology , Neospora/isolation & purification , Anemia, Hemolytic, Autoimmune/drug therapy , Anemia, Hemolytic, Autoimmune/immunology , Animals , Coccidiosis/immunology , Coccidiosis/parasitology , Dogs , Fatal Outcome , Female , Immunocompromised HostSubject(s)
Anemia, Hemolytic, Autoimmune/chemically induced , Antimalarials/adverse effects , Mefloquine/adverse effects , Anemia, Hemolytic, Autoimmune/immunology , Anemia, Hemolytic, Autoimmune/parasitology , Antimalarials/therapeutic use , Humans , Malaria, Falciparum/drug therapy , Male , Mefloquine/therapeutic use , Middle AgedABSTRACT
A 30-year-old woman contracted Plasmodium falciparum malaria in the first trimester of her pregnancy while taking chloroquine for malaria prophylaxis. Her illness was characterized by hemolytic anemia with IgG1 coating of the surface of the erythrocytes and IgG3 in her serum. The hemolysis subsided following treatment of the malaria infection early in the third trimester. She delivered at term an infant who had hypoplasia of the right tibia and fibula and absence of the fifth ray of the right foot. The hemolytic process was attributed to the malaria infection, and the birth defect may have been related to the antimalarial therapy in the first trimester of pregnancy.