Limits...
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.

Show MeSH

Related in: MedlinePlus

High titers of auto-Abs against IFN-α, IL-17A, IL-17F, and IL-22 in the plasma from patients with APS-I. Anti–IFN-α, –IL-17A, –IL-17F, and –IL-22 circulating IgG titers were measured by multiplex particle-based flow cytometry in 33 samples from patients with APS-I and in 37 samples from healthy controls. FI is plotted on the y axis. Representative data for two experiments are shown.
© Copyright Policy - openaccess
Related In: Results  -  Collection

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

fig1: High titers of auto-Abs against IFN-α, IL-17A, IL-17F, and IL-22 in the plasma from patients with APS-I. Anti–IFN-α, –IL-17A, –IL-17F, and –IL-22 circulating IgG titers were measured by multiplex particle-based flow cytometry in 33 samples from patients with APS-I and in 37 samples from healthy controls. FI is plotted on the y axis. Representative data for two experiments are shown.

Mentions: We searched for auto-Abs against IL-17 cytokines (IL-17A, IL-17F, IL-22, and IL-26, which is absent from mice) or against IL-17–inducing cytokines (IL-1β, IL-6, IL-21, IL-23, and TGF-β) in 33 patients diagnosed with APS-I on the basis of autoimmune polyendocrinopathy, circulating auto-Abs against IFN-α and –ω, and the presence of two mutant AIRE alleles (Table I). CMC was observed in 29 out of the 33 patients (Table I). Multiplex particle-based flow cytometry revealed a high fluorescence intensity (FI; >1,000, arbitrary definition) of IgG auto-Abs against IL-17A in the plasma of 22 patients, with a high FI of auto-Abs against IL-17F in 31 patients and of auto-Abs against IL-22 in 30 patients (Fig. 1 and Table I). All 33 patients had significant (P = 6.4 × 10−9, 4.6 × 10−12, and 2.16 × 10−11, respectively) levels of auto-Abs against at least one of these three cytokines. 5 patients had a significant reaction against a single cytokine, 6 had a reaction against two cytokines, and 22 had a reaction against all three cytokines. No auto-Abs against IL-17A, IL-17F, and IL-22 were found in plasma samples from the 37 healthy individuals tested. Similarly, no auto-Abs against any of these three cytokines were found in plasma samples from another 103 patients with various autoimmune conditions (Fig. S4, A and B). No auto-Abs against IL-1β, IL-6, IL-23, or IL-26 (whether as a monomer or a dimer) were found in the APS-I patients (Fig. S3, A–D). There were no auto-Abs against IL-12, IFN-γ, or GM-CSF (Fig. S3, E–G), consistent with the lack of mycobacterial disease and alveolar proteinosis in patients with APS-I. No auto-Abs were found against any of the other cytokines tested, including IL-10, IL-18, IFN-β, and TNF (Fig. S3, H–K). As expected, all APS-I patients had auto-Abs against IFN-α (Fig. 1 and Table I) and IFN-ω (not depicted). In addition, no IgA antibodies, a key element of mucosal immunity, directed against IL-17A, IL-17F, or IL-22 were detected in the plasma of 21 APS-I patients by classical ELISA (not depicted).


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)

High titers of auto-Abs against IFN-α, IL-17A, IL-17F, and IL-22 in the plasma from patients with APS-I. Anti–IFN-α, –IL-17A, –IL-17F, and –IL-22 circulating IgG titers were measured by multiplex particle-based flow cytometry in 33 samples from patients with APS-I and in 37 samples from healthy controls. FI is plotted on the y axis. Representative data for two experiments are shown.
© Copyright Policy - openaccess
Related In: Results  -  Collection

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

fig1: High titers of auto-Abs against IFN-α, IL-17A, IL-17F, and IL-22 in the plasma from patients with APS-I. Anti–IFN-α, –IL-17A, –IL-17F, and –IL-22 circulating IgG titers were measured by multiplex particle-based flow cytometry in 33 samples from patients with APS-I and in 37 samples from healthy controls. FI is plotted on the y axis. Representative data for two experiments are shown.
Mentions: We searched for auto-Abs against IL-17 cytokines (IL-17A, IL-17F, IL-22, and IL-26, which is absent from mice) or against IL-17–inducing cytokines (IL-1β, IL-6, IL-21, IL-23, and TGF-β) in 33 patients diagnosed with APS-I on the basis of autoimmune polyendocrinopathy, circulating auto-Abs against IFN-α and –ω, and the presence of two mutant AIRE alleles (Table I). CMC was observed in 29 out of the 33 patients (Table I). Multiplex particle-based flow cytometry revealed a high fluorescence intensity (FI; >1,000, arbitrary definition) of IgG auto-Abs against IL-17A in the plasma of 22 patients, with a high FI of auto-Abs against IL-17F in 31 patients and of auto-Abs against IL-22 in 30 patients (Fig. 1 and Table I). All 33 patients had significant (P = 6.4 × 10−9, 4.6 × 10−12, and 2.16 × 10−11, respectively) levels of auto-Abs against at least one of these three cytokines. 5 patients had a significant reaction against a single cytokine, 6 had a reaction against two cytokines, and 22 had a reaction against all three cytokines. No auto-Abs against IL-17A, IL-17F, and IL-22 were found in plasma samples from the 37 healthy individuals tested. Similarly, no auto-Abs against any of these three cytokines were found in plasma samples from another 103 patients with various autoimmune conditions (Fig. S4, A and B). No auto-Abs against IL-1β, IL-6, IL-23, or IL-26 (whether as a monomer or a dimer) were found in the APS-I patients (Fig. S3, A–D). There were no auto-Abs against IL-12, IFN-γ, or GM-CSF (Fig. S3, E–G), consistent with the lack of mycobacterial disease and alveolar proteinosis in patients with APS-I. No auto-Abs were found against any of the other cytokines tested, including IL-10, IL-18, IFN-β, and TNF (Fig. S3, H–K). As expected, all APS-I patients had auto-Abs against IFN-α (Fig. 1 and Table I) and IFN-ω (not depicted). In addition, no IgA antibodies, a key element of mucosal immunity, directed against IL-17A, IL-17F, or IL-22 were detected in the plasma of 21 APS-I patients by classical ELISA (not depicted).

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