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Potential plasma markers of Type 1 and Type 2 leprosy reactions: a preliminary report.

Stefani MM, Guerra JG, Sousa AL, Costa MB, Oliveira ML, Martelli CT, Scollard DM - BMC Infect. Dis. (2009)

Bottom Line: Elevations of plasma CXCL10 (P = 0.004) and IL6 (p = 0.013) were observed in T1R patients compared to controls without reaction.RANTES and GMCSF were excluded due to values above and below detection limit respectively in all samples.Potential biomarkers of T1R identified were CXCL10 and IL6 whereas IL7, PDGF-BB and IL6, may be laboratory markers of TR2.

View Article: PubMed Central - HTML - PubMed

Affiliation: Tropical Pathology and Public Health Institute, Federal University of Goias, GO, Brazil. mariane.stefani@pq.cnpq.br

ABSTRACT

Background: The clinical management of leprosy Type 1 (T1R) and Type 2 (T2R) reactions pose challenges mainly because they can cause severe nerve injury and disability. No laboratory test or marker is available for the diagnosis or prognosis of leprosy reactions. This study simultaneously screened plasma factors to identify circulating biomarkers associated with leprosy T1R and T2R among patients recruited in Goiania, Central Brazil.

Methods: A nested case-control study evaluated T1R (n = 10) and TR2 (n = 10) compared to leprosy patients without reactions (n = 29), matched by sex and age-group (+/- 5 years) and histopathological classification. Multiplex bead based technique provided profiles of 27 plasma factors including 16 pro inflammatory cytokines: tumor necrosis factor-alpha (TNF-alpha), Interferon-gamma (IFN-gamma), interleukin (IL)- IL12p70, IL2, IL17, IL1 beta, IL6, IL15, IL5, IL8, macrophage inflammatory protein (MIP)-1 alpha (MIP1alpha), 1 beta (MIP1beta), regulated upon activation normal T-cell expressed and secreted (RANTES), monocyte chemoattractrant protein 1 (MCP1), CC-chemokine 11 (CCL11/Eotaxin), CXC-chemokine 10 (CXCL10/IP10); 4 anti inflammatory interleukins: IL4, IL10, IL13, IL1Ralpha and 7 growth factors: IL7, IL9, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), platelet-derived growth factor BB (PDGF BB), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF).

Results: Elevations of plasma CXCL10 (P = 0.004) and IL6 (p = 0.013) were observed in T1R patients compared to controls without reaction. IL6 (p = 0.05), IL7 (p = 0.039), and PDGF-BB (p = 0.041) were elevated in T2R. RANTES and GMCSF were excluded due to values above and below detection limit respectively in all samples.

Conclusion: Potential biomarkers of T1R identified were CXCL10 and IL6 whereas IL7, PDGF-BB and IL6, may be laboratory markers of TR2. Additional studies on these biomarkers may help understand the immunopathologic mechanisms of leprosy reactions and indicate their usefulness for the diagnosis and for the clinical management of these events.

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Related in: MedlinePlus

Distribution of cytokines among Type 2 reaction leprosy patients (traced boxes) and controls without reaction (white boxes). (A) Pro inflammatory Cytokines (B) Anti Inflammatory cytokines (C) Growth Factors, IL-7 and PDGF-BB median values were statistically higher among cases than in the control group. Boxes encompass 25th and 75th percentiles of each cytokine distribution. Black lines within boxes refer to the median values.
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Figure 2: Distribution of cytokines among Type 2 reaction leprosy patients (traced boxes) and controls without reaction (white boxes). (A) Pro inflammatory Cytokines (B) Anti Inflammatory cytokines (C) Growth Factors, IL-7 and PDGF-BB median values were statistically higher among cases than in the control group. Boxes encompass 25th and 75th percentiles of each cytokine distribution. Black lines within boxes refer to the median values.

Mentions: Box plots distributions indicate differences in median plasma concentrations for all of the 15 inflammatory cytokines stratified by T1R cases and controls (Figure 1A) and T2R and controls (Figure 2A). The difference of CXCL10 median plasma concentration among T1R and their matched controls was highly significant (p = 0.004) (Fig 1A). IL6 also showed statistically significant differences between T1R patients and matched controls (p = 0.013) (Fig. 1A), while the difference for T2R patients and matched controls did not reach statistical significance (P = 0.05) (Fig. 2A). The differences between medians of CCL11 concentrations among T2R (363.6 pg/ml) and controls (218.6 pg/ml) were notable but not statistically significant (p = 0.06) (Fig. 2A).


Potential plasma markers of Type 1 and Type 2 leprosy reactions: a preliminary report.

Stefani MM, Guerra JG, Sousa AL, Costa MB, Oliveira ML, Martelli CT, Scollard DM - BMC Infect. Dis. (2009)

Distribution of cytokines among Type 2 reaction leprosy patients (traced boxes) and controls without reaction (white boxes). (A) Pro inflammatory Cytokines (B) Anti Inflammatory cytokines (C) Growth Factors, IL-7 and PDGF-BB median values were statistically higher among cases than in the control group. Boxes encompass 25th and 75th percentiles of each cytokine distribution. Black lines within boxes refer to the median values.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2696458&req=5

Figure 2: Distribution of cytokines among Type 2 reaction leprosy patients (traced boxes) and controls without reaction (white boxes). (A) Pro inflammatory Cytokines (B) Anti Inflammatory cytokines (C) Growth Factors, IL-7 and PDGF-BB median values were statistically higher among cases than in the control group. Boxes encompass 25th and 75th percentiles of each cytokine distribution. Black lines within boxes refer to the median values.
Mentions: Box plots distributions indicate differences in median plasma concentrations for all of the 15 inflammatory cytokines stratified by T1R cases and controls (Figure 1A) and T2R and controls (Figure 2A). The difference of CXCL10 median plasma concentration among T1R and their matched controls was highly significant (p = 0.004) (Fig 1A). IL6 also showed statistically significant differences between T1R patients and matched controls (p = 0.013) (Fig. 1A), while the difference for T2R patients and matched controls did not reach statistical significance (P = 0.05) (Fig. 2A). The differences between medians of CCL11 concentrations among T2R (363.6 pg/ml) and controls (218.6 pg/ml) were notable but not statistically significant (p = 0.06) (Fig. 2A).

Bottom Line: Elevations of plasma CXCL10 (P = 0.004) and IL6 (p = 0.013) were observed in T1R patients compared to controls without reaction.RANTES and GMCSF were excluded due to values above and below detection limit respectively in all samples.Potential biomarkers of T1R identified were CXCL10 and IL6 whereas IL7, PDGF-BB and IL6, may be laboratory markers of TR2.

View Article: PubMed Central - HTML - PubMed

Affiliation: Tropical Pathology and Public Health Institute, Federal University of Goias, GO, Brazil. mariane.stefani@pq.cnpq.br

ABSTRACT

Background: The clinical management of leprosy Type 1 (T1R) and Type 2 (T2R) reactions pose challenges mainly because they can cause severe nerve injury and disability. No laboratory test or marker is available for the diagnosis or prognosis of leprosy reactions. This study simultaneously screened plasma factors to identify circulating biomarkers associated with leprosy T1R and T2R among patients recruited in Goiania, Central Brazil.

Methods: A nested case-control study evaluated T1R (n = 10) and TR2 (n = 10) compared to leprosy patients without reactions (n = 29), matched by sex and age-group (+/- 5 years) and histopathological classification. Multiplex bead based technique provided profiles of 27 plasma factors including 16 pro inflammatory cytokines: tumor necrosis factor-alpha (TNF-alpha), Interferon-gamma (IFN-gamma), interleukin (IL)- IL12p70, IL2, IL17, IL1 beta, IL6, IL15, IL5, IL8, macrophage inflammatory protein (MIP)-1 alpha (MIP1alpha), 1 beta (MIP1beta), regulated upon activation normal T-cell expressed and secreted (RANTES), monocyte chemoattractrant protein 1 (MCP1), CC-chemokine 11 (CCL11/Eotaxin), CXC-chemokine 10 (CXCL10/IP10); 4 anti inflammatory interleukins: IL4, IL10, IL13, IL1Ralpha and 7 growth factors: IL7, IL9, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), platelet-derived growth factor BB (PDGF BB), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF).

Results: Elevations of plasma CXCL10 (P = 0.004) and IL6 (p = 0.013) were observed in T1R patients compared to controls without reaction. IL6 (p = 0.05), IL7 (p = 0.039), and PDGF-BB (p = 0.041) were elevated in T2R. RANTES and GMCSF were excluded due to values above and below detection limit respectively in all samples.

Conclusion: Potential biomarkers of T1R identified were CXCL10 and IL6 whereas IL7, PDGF-BB and IL6, may be laboratory markers of TR2. Additional studies on these biomarkers may help understand the immunopathologic mechanisms of leprosy reactions and indicate their usefulness for the diagnosis and for the clinical management of these events.

Show MeSH
Related in: MedlinePlus