Evaluation of an Enzyme-Linked Immunosorbent Assay Based on Crude Leishmania Histone Proteins for Serodiagnosis of Human Infantile Visceral Leishmaniasis

Lakhal, Sami; Mekki, Salima; Ben-Abda, Imène; Mousli, Mohamed; Amri, Fethi; Karim, Abdul; Bouratbine, A.

doi:10.1128/cvi.00257-12

Cited by 20 publications

(17 citation statements)

References 43 publications

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“…Soluble Leishmania Antigen/SLA was prepared from L. infantum promastigotes after ultrasonic treatment, as described previously [22,23]. Crude Leishmania Histones (CLH) were extracted according to a standard approach of histone protein isolation [24] with some modifications [23,24].…”

Section: Antigensmentioning

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.…”

Section: Antigensmentioning

confidence: 99%

“…Antibodies against CLH, SLA and rK39 were detected by ELISA, as described previously [23]. Antibodies against rH2A, rH2B and rH4 were detected as follows.…”

Section: Detection Of Antigen-specific Antibodies By Enzyme Linked Immentioning

confidence: 99%

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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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Section: Antigensmentioning

confidence: 99%

Section: Antigensmentioning

confidence: 99%

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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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“…The consideration of the latter environmental features depicted above were incentives to add (a) to the classical SLE associated autoantigen panels, the recombinant rK39 and additionally two antigenic crude mixtures from L. infantum-e.g., L. infantum Soluble Leishmania Antigen (SLA) and Crude Leishmania histone (CLH) [12].…”

Section: Commentarymentioning

confidence: 99%

“…Two antigenic crude mixtures from L. infantum-e.g., L. infantum Soluble Leishmania Antigen (SLA) and Crude Leishmania histone (CLH) [10][11][12], Soluble Leishmania antigens (SLA) evolutionarily conserved proteins such as Leishmania histones have shown serodiagnostic potential features for human and canine VL [8,10].…”

Section: Commentarymentioning

confidence: 99%

Sera of Human Beings Hosting Durably Viscerotropic Leishmania Species Display Histones- Binding Immunoglobulins: A Feature To Consider When Probing Signatures of Auto-Reactivity?

Lakhal¹,

Younes²

2016

J Clin Cell Immunol

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When being asked to extract molecular immune signatures, at the preclinical stage of systemic lupus erythematosus (SLE), the analysts who received the subjects' blood, monitor the presence and titers of autoantibodies against a more or less extended panel of SLE associated autoantigens. Tunisian subjects are known to stably share habitats where zoo anthropophilic blood-feeding sand flies and Leishmania infantum co-perpetuate. We were curious to add three other antigenic sources depicted below. Two serum biobanks were selected in the original publication. Analysis from the second shown, four sera containing high titers of mammalian histones autoantibodies as well as a range of ENA-binding autoantibodies. Combined tests that allow detecting antibodies signing [1] risks of developing SLE [2] as well as exposure to viscerotropic Leishmania species, whenever physicians addressed blood of healthy subjects inhabiting areas where perpetuate these species L. chagasi/infantum and L. donovani. L. donovani is the second species within the genus Leishmania to share these so-called viscerotropic features with L. chagasi/infantum.We were not in the position to disentangle the genetic and environmental components that could account for the multiple positive serologic tests in healthy subjects.It will be important to broaden the spectrum of differential diagnoses in healthy subjects at risk of developing auto immune diseases when they stably inhabit areas where sand flies and viscerotropic Leishmania species coperpetuate. Keywords: Systemic Lupus Erythematosus; SLE-associated autoantigen panels; Autoantibodies; Viscerotropic Leishmania species CommentaryIn the publication [1] commented here, the Systemic Lupus Erythematosus (SLE) associated autoantigens were (a) HEp-2 cells substrate with a native protein array with hundreds of antigens, provides an ideal substrate for the detection of ANA allowing the autoantibodies to be detected by Indirect Immunofluorescence (IIF) cell [2]. The detection of ANA in human serum is an important screening tool for SLE, and IIF is the gold method for ANA testing [2].Since the blood samples were collected from Tunisian subjects, we were curious to add three other antigenic sources depicted below to the above mentioned SLE associated autoantigens [3] and (b) human histones rich extracted nuclear auto-antigens (ENA) kits, these autoantibodies being detected and quantified by ELISA.Indeed, Tunisian subjects are known to stably share habitats where zooanthropophilic blood-feeding sand flies and Leishmania/L. infantum co-perpetuate. The completion of the developmental program of the latter eukaryotic single celled parasite is known to proceed through blood-feeding sand flies and mammals such as dogs and human beings [4][5][6].Briefly, once deposited, in the upper dermis, by the sand fly over its blood meal, the mammal pre-adapted L. infantum population of metacyclic promastigotes are rapidly internalized by mononuclear phagocytes/macrophages and dendritic cells.

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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

et al. 2014

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Visceral leishmaniasis has been associated with hyper-gammaglobulinemia and antinuclear antibodies and may simulate systemic lupus erythematosus. Sera from patients with visceral leishmaniasis have been shown to strongly react against conserved proteins from the parasite, such as ribosomal and histones. Some of these proteins have also been described as immunogenic in several auto-immune syndromes, and the detection of antibodies against them is considered to be indicative of disorder in the immune system. This study aimed to assess by enzyme-linked immunosorbent assay, test routinely employed in visceral leishmaniasis diagnosis, the recognition of Crude Leishmania histone and Soluble Leishmania antigens proteins from Leishmania infantum by adult patients with suggestive signs of autoimmune diseases. Our results show that the humoral response generated during autoimmune diseases cross-reacts with the parasitic Crude Leishmania histone and Soluble Leishmania antigens. In these cases, higher precautions must be taken to confirm the presence of visceral leishmaniasis in front of positive serology in antinuclear antibodies positive sera, in order to avoid wrong diagnosis.

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Evaluation of an Enzyme-Linked Immunosorbent Assay Based on Crude Leishmania Histone Proteins for Serodiagnosis of Human Infantile Visceral Leishmaniasis

Cited by 20 publications

References 43 publications

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

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

Sera of Human Beings Hosting Durably Viscerotropic Leishmania Species Display Histones- Binding Immunoglobulins: A Feature To Consider When Probing Signatures of Auto-Reactivity?

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

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