The significance of blood levels of IgM, IgA, IgG and IgG subclasses in Sudanese visceral leishmaniasis patients

Elassad, A. M. S.; Younis, Suhaila; Siddig, Mohammed; Grayson, Jane; Petersen, Eskild A.; Ghalib, H. W.

doi:10.1111/j.1365-2249.1994.tb06526.x

Cited by 46 publications

(14 citation statements)

References 26 publications

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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%

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

Yang

Mosser

Zhang

2007

The Journal of Immunology

115

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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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

115

124

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“…Anam et al (144) also hinted at a possible (diagnostic) role for L. donovani-specific IgG3 antibody isotype detection. While the IgG3 antibody level decreases significantly posttreatment (148,149), the pharmacodynamic value of this marker is probably very low, as the time to normalcy for IgGs is longer than 3 months for both CL and VL patients (150)(151)(152)(153)(154).…”

Section: Identified Biomarkersmentioning

confidence: 99%

Systematic Review of Biomarkers To Monitor Therapeutic Response in Leishmaniasis

Kip

Balasegaram

Beijnen

et al. 2015

Antimicrob Agents Chemother

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e Recently, there has been a renewed interest in the development of new drugs for the treatment of leishmaniasis. This has spurred the need for pharmacodynamic markers to monitor and compare therapies specifically for visceral leishmaniasis, in which the primary recrudescence of parasites is a particularly long-term event that remains difficult to predict. We performed a systematic review of studies evaluating biomarkers in human patients with visceral, cutaneous, and post-kala-azar dermal leishmaniasis, which yielded a total of 170 studies in which 53 potential pharmacodynamic biomarkers were identified. In conclusion, the large majority of these biomarkers constituted universal indirect markers of activation and subsequent waning of cellular immunity and therefore lacked specificity. Macrophage-related markers demonstrate favorable sensitivity and times to normalcy, but more evidence is required to establish a link between these markers and clinical outcome. Most promising are the markers directly related to the parasite burden, but future effort should be focused on optimization of molecular or antigenic targets to increase the sensitivity of these markers. In general, future research should focus on the longitudinal evaluation of the pharmacodynamic biomarkers during treatment, with an emphasis on the correlation of studied biomarkers and clinical parameters.

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“…When antileishmanial antibody level was compared between children and adult samples of KA and PKDL sera, significantly elevated levels of IgG3 and IgG4 were evident in children cases compared to adult KA cases. Investigations of IgG subclass in Sudanese patients have shown maximum generation of IgG3 and IgG4 (35).…”

Section: Discussionmentioning

confidence: 99%

Elevated levels of IgG3 and IgG4 subclass in paediatric cases of kala azar

Ansari

Kumar

Raj

et al. 2008

Parasite Immunology

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Visceral leishmaniasis (VL) or Kala azar (KA) is a systemic disease caused by the parasites of the Leishmania donovani complex. Control measures rely on treatment with antileishmanial agents, however, fraught with problems such as toxicity or drug resistance. The incidence rate is on the rise for children, for reasons yet undefined. Previously we have shown significantly elevated level of IL-10 in children compared to adult KA cases. Here, antileishmanial antibody and C-reactive protein (CRP) levels were investigated in paediatrics and adult patients of KA and post-KA dermal leishmaniasis (PKDL). Level of IgG4 was significantly elevated in PKDL compared to KA, although total IgG and IgG1 were significantly lower. The antileishmania antibody levels of subclass IgG3 and IgG4 were found significantly elevated in paediatrics, however, levels of IgG, IgG1, IgG2 and CRP were comparable in paediatric and adult KA cases. In case of PKDL, levels of IgG and it subclass were similar in the two groups. No significant difference in antileishmanial antibody level was noticed between macular or polymorphic cases of PKDL. The differential antibody intensity in paediatric cases, together with significant level of circulating IL-10, could be considered as a marker of differential disease susceptibility.

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The significance of blood levels of IgM, IgA, IgG and IgG subclasses in Sudanese visceral leishmaniasis patients

Cited by 46 publications

References 26 publications

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

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

Systematic Review of Biomarkers To Monitor Therapeutic Response in Leishmaniasis

Elevated levels of IgG3 and IgG4 subclass in paediatric cases of kala azar

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