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Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I.

Puel A, Döffinger R, Natividad A, Chrabieh M, Barcenas-Morales G, Picard C, Cobat A, Ouachée-Chardin M, Toulon A, Bustamante J, Al-Muhsen S, Al-Owain M, Arkwright PD, Costigan C, McConnell V, Cant AJ, Abinun M, Polak M, Bougnères PF, Kumararatne D, Marodi L, Nahum A, Roifman C, Blanche S, Fischer A, Bodemer C, Abel L, Lilic D, Casanova JL - J. Exp. Med. (2010)

Bottom Line: The auto-Abs against IL-17A were neutralizing in the only patient tested, as shown by bioassays of IL-17A activity.None of the 37 healthy controls and none of the 103 patients with other autoimmune disorders tested had such auto-Abs.None of the patients with APS-I had auto-Abs against cytokines previously shown to cause other well-defined clinical syndromes in other patients (IL-6, interferon [IFN]-gamma, or granulocyte/macrophage colony-stimulating factor) or against other cytokines (IL-1beta, IL-10, IL-12, IL-18, IL-21, IL-23, IL-26, IFN-beta, tumor necrosis factor [alpha], or transforming growth factor beta).

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM), U550, 75015 Paris, France. anne.puel@inserm.fr

ABSTRACT
Most patients with autoimmune polyendocrine syndrome type I (APS-I) display chronic mucocutaneous candidiasis (CMC). We hypothesized that this CMC might result from autoimmunity to interleukin (IL)-17 cytokines. We found high titers of autoantibodies (auto-Abs) against IL-17A, IL-17F, and/or IL-22 in the sera of all 33 patients tested, as detected by multiplex particle-based flow cytometry. The auto-Abs against IL-17A, IL-17F, and IL-22 were specific in the five patients tested, as shown by Western blotting. The auto-Abs against IL-17A were neutralizing in the only patient tested, as shown by bioassays of IL-17A activity. None of the 37 healthy controls and none of the 103 patients with other autoimmune disorders tested had such auto-Abs. None of the patients with APS-I had auto-Abs against cytokines previously shown to cause other well-defined clinical syndromes in other patients (IL-6, interferon [IFN]-gamma, or granulocyte/macrophage colony-stimulating factor) or against other cytokines (IL-1beta, IL-10, IL-12, IL-18, IL-21, IL-23, IL-26, IFN-beta, tumor necrosis factor [alpha], or transforming growth factor beta). These findings suggest that auto-Abs against IL-17A, IL-17F, and IL-22 may cause CMC in patients with APS-I.

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Specific auto-Abs against IL-17A, IL-17F, and/or IL-22 in the plasma from patients with APS-I. Western blot against rIL-17A, rIL-17F, rIL-22, and rIL-23 were performed using plasma from a healthy individual or from five patients with APS-I, diluted 1:500. Representative data for three experiments are shown. Dashed lines indicate that intervening lanes have been spliced out.
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fig2: Specific auto-Abs against IL-17A, IL-17F, and/or IL-22 in the plasma from patients with APS-I. Western blot against rIL-17A, rIL-17F, rIL-22, and rIL-23 were performed using plasma from a healthy individual or from five patients with APS-I, diluted 1:500. Representative data for three experiments are shown. Dashed lines indicate that intervening lanes have been spliced out.

Mentions: We performed Western blotting to assess the specificity of these auto-Abs. Plasma samples from five patients with APS-I and auto-Abs against IL-17A, IL-17F, and/or IL-22, as detected by ELISA and multiplex particle-based flow cytometry, and from a healthy individual were tested for their ability to recognize rIL-17A, rIL-17F, and rIL-22 on Western blots. The three cytokines were clearly recognized by plasma samples from patients but not by the control plasma (Fig. 2). The plasma samples from patients did not recognize IL-23 in a control assay. Finally, we investigated whether the auto-Abs against IL-17A neutralized this cytokine in a simple biological assay. We incubated fibroblasts from a healthy control with up to 50 ng/ml rIL-17A in the presence of plasma from healthy individuals, or from a patient with APS-I and auto-Abs against IL-17, as detected by ELISA and Western blotting. We then measured the induction of IL-6 by ELISA on the supernatant. Strikingly, even strong dilutions of plasma samples from patients (up to 0.1%; not depicted) completely abolished fibroblastic cell responses to such high concentrations of rIL-17 (Fig. 3), whereas control plasma had no effect. Lower concentrations of IL-17A failed to induce IL-6, even in the presence of control plasma (unpublished data). The lack of robust bioassays precluded assessments of the possible neutralizing effects of auto-Abs against IL-17F and IL-22. Thus, all patients with APS-I tested had high titers of auto-Abs against IL-17A, IL-17F, and IL-22 in their plasma, and these auto-Abs were specific and neutralizing, at least in the patients tested. These data suggest that most patients with APS-I carry neutralizing auto-Abs against IL-17A, IL-17F, and IL-22.


Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I.

Puel A, Döffinger R, Natividad A, Chrabieh M, Barcenas-Morales G, Picard C, Cobat A, Ouachée-Chardin M, Toulon A, Bustamante J, Al-Muhsen S, Al-Owain M, Arkwright PD, Costigan C, McConnell V, Cant AJ, Abinun M, Polak M, Bougnères PF, Kumararatne D, Marodi L, Nahum A, Roifman C, Blanche S, Fischer A, Bodemer C, Abel L, Lilic D, Casanova JL - J. Exp. Med. (2010)

Specific auto-Abs against IL-17A, IL-17F, and/or IL-22 in the plasma from patients with APS-I. Western blot against rIL-17A, rIL-17F, rIL-22, and rIL-23 were performed using plasma from a healthy individual or from five patients with APS-I, diluted 1:500. Representative data for three experiments are shown. Dashed lines indicate that intervening lanes have been spliced out.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2822614&req=5

fig2: Specific auto-Abs against IL-17A, IL-17F, and/or IL-22 in the plasma from patients with APS-I. Western blot against rIL-17A, rIL-17F, rIL-22, and rIL-23 were performed using plasma from a healthy individual or from five patients with APS-I, diluted 1:500. Representative data for three experiments are shown. Dashed lines indicate that intervening lanes have been spliced out.
Mentions: We performed Western blotting to assess the specificity of these auto-Abs. Plasma samples from five patients with APS-I and auto-Abs against IL-17A, IL-17F, and/or IL-22, as detected by ELISA and multiplex particle-based flow cytometry, and from a healthy individual were tested for their ability to recognize rIL-17A, rIL-17F, and rIL-22 on Western blots. The three cytokines were clearly recognized by plasma samples from patients but not by the control plasma (Fig. 2). The plasma samples from patients did not recognize IL-23 in a control assay. Finally, we investigated whether the auto-Abs against IL-17A neutralized this cytokine in a simple biological assay. We incubated fibroblasts from a healthy control with up to 50 ng/ml rIL-17A in the presence of plasma from healthy individuals, or from a patient with APS-I and auto-Abs against IL-17, as detected by ELISA and Western blotting. We then measured the induction of IL-6 by ELISA on the supernatant. Strikingly, even strong dilutions of plasma samples from patients (up to 0.1%; not depicted) completely abolished fibroblastic cell responses to such high concentrations of rIL-17 (Fig. 3), whereas control plasma had no effect. Lower concentrations of IL-17A failed to induce IL-6, even in the presence of control plasma (unpublished data). The lack of robust bioassays precluded assessments of the possible neutralizing effects of auto-Abs against IL-17F and IL-22. Thus, all patients with APS-I tested had high titers of auto-Abs against IL-17A, IL-17F, and IL-22 in their plasma, and these auto-Abs were specific and neutralizing, at least in the patients tested. These data suggest that most patients with APS-I carry neutralizing auto-Abs against IL-17A, IL-17F, and IL-22.

Bottom Line: The auto-Abs against IL-17A were neutralizing in the only patient tested, as shown by bioassays of IL-17A activity.None of the 37 healthy controls and none of the 103 patients with other autoimmune disorders tested had such auto-Abs.None of the patients with APS-I had auto-Abs against cytokines previously shown to cause other well-defined clinical syndromes in other patients (IL-6, interferon [IFN]-gamma, or granulocyte/macrophage colony-stimulating factor) or against other cytokines (IL-1beta, IL-10, IL-12, IL-18, IL-21, IL-23, IL-26, IFN-beta, tumor necrosis factor [alpha], or transforming growth factor beta).

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM), U550, 75015 Paris, France. anne.puel@inserm.fr

ABSTRACT
Most patients with autoimmune polyendocrine syndrome type I (APS-I) display chronic mucocutaneous candidiasis (CMC). We hypothesized that this CMC might result from autoimmunity to interleukin (IL)-17 cytokines. We found high titers of autoantibodies (auto-Abs) against IL-17A, IL-17F, and/or IL-22 in the sera of all 33 patients tested, as detected by multiplex particle-based flow cytometry. The auto-Abs against IL-17A, IL-17F, and IL-22 were specific in the five patients tested, as shown by Western blotting. The auto-Abs against IL-17A were neutralizing in the only patient tested, as shown by bioassays of IL-17A activity. None of the 37 healthy controls and none of the 103 patients with other autoimmune disorders tested had such auto-Abs. None of the patients with APS-I had auto-Abs against cytokines previously shown to cause other well-defined clinical syndromes in other patients (IL-6, interferon [IFN]-gamma, or granulocyte/macrophage colony-stimulating factor) or against other cytokines (IL-1beta, IL-10, IL-12, IL-18, IL-21, IL-23, IL-26, IFN-beta, tumor necrosis factor [alpha], or transforming growth factor beta). These findings suggest that auto-Abs against IL-17A, IL-17F, and IL-22 may cause CMC in patients with APS-I.

Show MeSH
Related in: MedlinePlus