Mixed cryoglobulinemia secondary to visceral Leishmaniasis

Casato, Milvia; Rosa, Francesco Giuseppe De; Pucillo, Leopoldo Paolo; Ilardi, I; Vico, Bruno Di; Zorzin, L.; Sorgi, Maria Laura; Fiaschetti, P.; Coviello, Rossella; Laganà, Bruno; Fiorilli, Massimo

doi:10.1002/1529-0131(199909)42:9<2007::aid-anr30>3.0.co;2-x

Cited by 30 publications

(23 citation statements)

References 12 publications

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“…2,3 Visceral leishmaniasis has also been implicated as a cause of cryoglobulinemia. 5 These manifestations of visceral leishmaniasis have been proposed to be a result of chronic antigenic stimulation that occurs in these patients. 4 Monoclonal gammopathy associated with visceral leishmaniasis should be distinguished from monoclonal gammopathy of undetermined significance (MGUS).…”

Section: Discussionmentioning

confidence: 99%

Monoclonal gammopathy associated with visceral leishmaniasis

Sharma¹,

Agarwal²,

Giri³

2010

Braz J Infect Dis

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Monoclonal gammopathy can accompany diverse conditions and is usually benign. It should be distinguished from monoclonal gammopathy of undetermined signifi cance (MGUS) which can rarely turn malignant. Visceral leishmaniasis has only rarely been associated with monoclonal gammopathy. We describe the case of a 55-year-old male who had monoclonal gammopathy associated with visceral leishmanisais, which reversed with stibogluconate therapy.

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Section: Discussionmentioning

confidence: 99%

Monoclonal gammopathy associated with visceral leishmaniasis

Sharma¹,

Agarwal²,

Giri³

2010

Braz J Infect Dis

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“…Several studies have demonstrated that high levels of parasite-specific IgG are generated during leishmaniasis (46,47). This is especially true with human visceral leishmaniasis in which rheumatoid factor (48 -50) and parasite-specific IgG levels are high (27)(28)(29)(30)(31)(32), making it more likely that amastigotes derived from lesions would be opsonized with host IgG. Our model would predict that disease exacerbation caused by immune complexes would only occur late in disease, after parasite-specific IgG was generated.…”

Section: Discussionmentioning

confidence: 99%

“…IgG Abs to Leishmania are prominent in human visceral leishmaniasis, and they are also produced in BALB/c mice during Leishmania infection (27)(28)(29)(30)(31)(32). The levels of IgG increase as disease progresses and parasites disseminate.…”

Section: Il-10 Reduces Ag Presentation and Either Inhibits Or Biases mentioning

confidence: 99%

Activation of the MAPK, ERK, following Leishmania amazonensis Infection of Macrophages

Yang

Mosser

Zhang

2007

The Journal of Immunology

114

124

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IL-10 is a critical cytokine in determining host susceptibility to Leishmania spp. We previously demonstrated that macrophage-derived IL-10 could contribute to disease exacerbation, but the mechanisms whereby Leishmania infections led to IL-10 induction were not fully understood. In this study, we demonstrated that infection of macrophages with Leishmania amazonensis amastigotes led to the activation of the MAPK, ERK1/2. This activation was required, but not sufficient for IL-10 induction. In addition to ERK activation, an inflammatory stimulus, such as low m.w. hyaluronic acid from the extracellular matrix, must also be present. The combination of these two signals resulted in the superinduction of IL-10. We also demonstrated that IgG on the surface of Leishmania amastigotes was required to achieve maximal IL-10 production from infected macrophages. Surface IgG engages macrophage FcγR to induce ERK activation. Macrophages lacking FcγR, or macrophages treated with an inhibitor of spleen tyrosine kinase, the tyrosine kinase that signals via FcγR, failed to activate ERK and consequently failed to produce IL-10 following infection with Leishmania amastigotes. We confirmed that ERK1/2 activation led to the phosphorylation of histone H3 at the IL-10 promoter, and this phosphorylation allowed for the binding of the transcription factor, Sp1, to the IL-10 promoter. Finally, the administration of U0126, an inhibitor of ERK activation, to infected mice resulted in decreased lesion progression with reduced numbers of parasites in them. Thus, our findings reveal an important role of MAPK, ERK signaling in the pathogenesis of Leishmania infection.

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“…infantum co-exist. Although the burden of VL in North Africa is mainly in children aged between 1 and 4 years of age, VL can present clinical and laboratory autoimmune manifestations including arthralgia, cutaneous vasculitis, increased titers of rheumatoid factor (RF) and antinuclear antibodies (ANA) [27][28][29]. VL patients may initially be misdiagnosed as having an autoimmune disease such as SLE or autoimmune hepatitis, leading to the possibility that they could be treated with immunosuppressive drugs with fatal consequences [30].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, we assessed crude mixtures of Leishmania histones (CLH) and the related single recombinant histones rH2A, rH2B and rH4 derived from L. infantum [27].…”

Section: Discussionmentioning

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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Mixed cryoglobulinemia secondary to visceral Leishmaniasis

Cited by 30 publications

References 12 publications

Monoclonal gammopathy associated with visceral leishmaniasis

Monoclonal gammopathy associated with visceral leishmaniasis

Activation of the MAPK, ERK, following Leishmania amazonensis Infection of Macrophages

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

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