The sera from adult patients with suggestive signs of autoimmune diseases present antinuclear autoantibodies that cross-react with Leishmania infantum conserved proteins: Crude Leishmania histone and Soluble Leishmnia antigens

Lakhal, Sami; Benabid, Meriem; Sghaier, Ikram; Bettaieb, Jihen; Bouratbine, A.; Galai, Yousr

doi:10.1007/s12026-014-8589-x

Cited by 8 publications

(5 citation statements)

References 29 publications

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“…A high percentage (30%) of patients were positive for auto-antibodies (commonly found in patients with VL) and for antibodies to other infectious agents (especially Borrelia and Coxiella ) (45%). VL can therefore be initially confused with autoimmune disease [23], and certainly the cross-reactivity of these auto-antibodies with the histone protein of Leishmania [24] has been described. Thus, patients with autoimmune disease but without VL may test positive for Leishmania serology in ELISA.…”

Section: Discussionmentioning

confidence: 99%

Clinical aspects of visceral leishmaniasis caused by L. infantum in adults. Ten years of experience of the largest outbreak in Europe: what have we learned?

et al. 2019

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Background An outbreak of leishmaniasis caused by Leishmania infantum was declared in the southwest of the Madrid region (Spain) in June 2009. This provided a unique opportunity to compare the management of visceral leishmaniasis (VL) in immunocompetent adults (IC-VL), patients with HIV (HIV-VL) and patients receiving immunosuppressants (IS-VL). Methods A cohort of adults with VL, all admitted to the Hospital Universitario de Fuenlabrada between June 2009 and June 2018, were monitored in this observational study, recording their personal, epidemiological, analytical, diagnostic, treatment and outcome variables. Results The study population was made up of 111 patients with VL (10% HIV-VL, 14% IS-VL, 76% IC-VL). Seventy-one percent of the patients were male; the mean age was 45 years (55 years for the IS-VL patients, P = 0.017). Fifty-four percent of the IC-VL patients were of sub-Saharan origin ( P = 0.001). Fever was experienced by 98% of the IC-VL patients vs 73% of the LV-HIV patients ( P = 0.003). Plasma ferritin was > 1000 ng/ml in 77% of the IC-VL patients vs 17% of the LV-HIV patients ( P = 0.007). Forty-two percent of patients fulfilled the criteria for haemophagocytic lymphohistiocytosis. RDT (rK39-ICT) serological analysis returned sensitivity and specificity values of 45% and 99%, respectively, and ELISA/iIFAT returned 96% and 89%, respectively, with no differences in this respect between patient groups. Fourteen (13.0%) patients with VL experienced treatment failure, eight of whom were in the IC-VL group. Treatment with < 21 mg/kg (total) liposomal amphotericin B (LAB) was associated with treatment failure in the IC-VL patients [ P = 0.002 (OR: 14.7; 95% CI: 2.6–83.3)]. Conclusions IS-VL was more common than HIV-VL; the lack of experience in dealing with IS-VL is a challenge that needs to be met. The clinical features of the patients in all groups were similar, although the HIV-VL patients experienced less fever and had lower plasma ferritin concentrations. RDT (rK39-ICT) analysis returned a good specificity value but a much poorer sensitivity value than reported in other scenarios. The patients with HIV-VL, IS-VL and IC-VL returned similar serological results. Current guidelines for treatment seem appropriate, but the doses of LAB required to treat patients with HIV-VL and IS-VL are poorly defined.

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Section: Discussionmentioning

confidence: 99%

Clinical aspects of visceral leishmaniasis caused by L. infantum in adults. Ten years of experience of the largest outbreak in Europe: what have we learned?

et al. 2019

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“…In addition, CLH-based ELISA showed an excellent ability to discriminate between VL cases and healthy controls (97.6% sensitivity and 100% specificity). However, humoral response generated in sera from subjects at risk of developing SLE episodes cross-reacts with the parasitic Crude Leishmania histone [23,25]. In fact, the native CLHbased ELISA was revealed more accurate than single recombinant histone-based ELISA in some subjects from the same control group prepared from healthy pregnant women living in North Tunisia, an area where L. infantum is endemic and was more specific.…”

Section: Discussionmentioning

confidence: 99%

“…Crude Leishmania Histones (CLH) were extracted according to a standard approach of histone protein isolation [24] with some modifications [23,24]. rK39, a recombinant product of the 39 amino acid repeats found in a kinesin-like gene of viscerotropic Leishmania species [25], was kindly provided by Dr. Steven G. Reed, infectious disease research institute (IDRI), Seattle, WA. L. infantum/chagasi derived recombinant proteins rH2A, rH2B, and rH4 were kindly provided by Dr. Manuel Soto Manuel Centro de Biologóa Molecular "Severo Ochoa", Facultad de Ciencias, Universidad Autonoma de Madrid, Madrid, Spain [11][12][13][14].…”

Section: Antigensmentioning

confidence: 99%

In Silico Identification of B-Cell Epitopes of Leishmania infantum Recombinant Histone Shared with Human Sera Stably Living in Area Where Leishmania Species Does Perpetuate

Lakhal¹,

Duthie²

2017

Next Generat Sequenc & Applic

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Visceral leishmaniasis (VL) can initially be misdiagnosed because its presentation is similar to many autoimmune diseases such as systemic lupus erythematosus (SLE), autoimmune hepatitis and dermatomyositis. Furthermore, serum antibodies from VL patients have been shown to strongly react against proteins that are conserved between the causative agent, L. infantum, and humans themselves. Some of these proteins, like histone, have also been described as immunogenic in several auto-immune syndromes, and the detection of antibodies against them is considered to be indicative of immune system disorders.The potential overlap of autoimmune diseases and VL presents a situation of confounding diagnoses if crossreactive tests are used. To explore this possibility, we screened sera from three Tunisian populations for the presence, and relative quantity, of antibodies against a panel of L. infantum antigens comprising crude extract or recombinant molecules, with special attention being given to evolutionarily conserved histones. Our data indicate that antibodies in many of the SLE at-risk individuals recognized crude soluble Leishmania antigen (SLA). This compromised the specificity of SLA-based ELISA, providing many results falsely indicating L. infantum infection. Examination of the crude Leihsmania histone (CLH) mixture, which is expected to contain nucleosomal Leishmania histones H2A, H2B and H4, as well as recombinant versions of these Leishmania histones, suggested these to be a source of the cross-reactivity. For the purposes of diagnosing VL, it is therefore important to note that the rK39 antigen was found to be more specific and not conflicting with autoimmune presentations. In silico prediction data validate and indicate that the human histones are immunologically cross-reactive with Leishmania histones.

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“…Clinical presentations and laboratory findings of VL and autoimmune diseases may overlap in some cases. The similarity in clinical presentations (fever, pallor, anorexia, malaise, weight loss, and hepatosplenomegaly) and laboratory findings (anemia, leucopenia, thrombocytopenia, hypergammaglobulinemia, hypoalbuminemia, low serum complement levels, high levels of inflammatory markers like ESR and CRP, and the presence of anti-dsDNA, C-ANCA, and P-ANCA) could therefore be misleading in differentiating VL from autoimmune diseases [ 10 , 11 ].…”

Section: Discussionmentioning

confidence: 99%

Autoantibodies in a Three-Year-Old Girl with Visceral Leishmaniasis: A Potential Diagnostic Pitfall

Pouladfar

Jafarpour

Babaei

et al. 2016

Case Reports in Infectious Diseases

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Visceral leishmaniasis (VL), a life-threatening parasitic infection, is endemic in the Mediterranean region. Diagnosis of VL is based on epidemiologic, clinical, and laboratory findings. However, sometimes, clinical features and laboratory findings overlap with those of autoimmune diseases. In some cases, autoantibodies are detected in patients with VL and this could be a potential diagnostic pitfall. In this study, we have reported on a three-year-old girl from a VL-endemic area in Iran, who presented with prolonged fever and splenomegaly. Bone marrow examination, serologic tests, and the molecular PCR assay were performed; however, results were inconclusive. The levels of anti-double stranded DNA, cytoplasmic antineutrophil cytoplasmic autoantibody, and perinuclear antineutrophil cytoplasmic autoantibody were elevated and, at the end, splenic biopsy was performed. The splenic tissue PCR test detected the DNA of Leishmania infantum. The patient's condition improved with anti-Leishmania therapy, and the autoantibodies disappeared within the following four months. Clinical presentations and laboratory findings of VL and autoimmune diseases may overlap in some patients.

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The sera from adult patients with suggestive signs of autoimmune diseases present antinuclear autoantibodies that cross-react with Leishmania infantum conserved proteins: Crude Leishmania histone and Soluble Leishmnia antigens

Cited by 8 publications

References 29 publications

Clinical aspects of visceral leishmaniasis caused by L. infantum in adults. Ten years of experience of the largest outbreak in Europe: what have we learned?

Clinical aspects of visceral leishmaniasis caused by L. infantum in adults. Ten years of experience of the largest outbreak in Europe: what have we learned?

In Silico Identification of B-Cell Epitopes of Leishmania infantum Recombinant Histone Shared with Human Sera Stably Living in Area Where Leishmania Species Does Perpetuate

Autoantibodies in a Three-Year-Old Girl with Visceral Leishmaniasis: A Potential Diagnostic Pitfall

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