Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I.
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.
Puel
Anne
A
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
Döffinger
Rainer
R
Natividad
Angels
A
Chrabieh
Maya
M
Barcenas-Morales
Gabriela
G
Picard
Capucine
C
Cobat
Aurélie
A
Ouachée-Chardin
Marie
M
Toulon
Antoine
A
Bustamante
Jacinta
J
Al-Muhsen
Saleh
S
Al-Owain
Mohammed
M
Arkwright
Peter D
PD
Costigan
Colm
C
McConnell
Vivienne
V
Cant
Andrew J
AJ
Abinun
Mario
M
Polak
Michel
M
Bougnères
Pierre-François
PF
Kumararatne
Dinakantha
D
Marodi
László
L
Nahum
Amit
A
Roifman
Chaim
C
Blanche
Stéphane
S
Fischer
Alain
A
Bodemer
Christine
C
Abel
Laurent
L
Lilic
Desa
D
Casanova
Jean-Laurent
JL
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D015551:Autoimmunity; D015153:Blotting, Western; D002178:Candidiasis, Chronic Mucocutaneous / Q000097:blood / Q000209:etiology / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology*; D007378:Interleukins / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016884:Polyendocrinopathies, Autoimmune / Q000097:blood / Q000150:complications / Q000276:immunology*; D055815:Young Adult; D000097043:Interleukin-22
D001323:Autoantibodies; D007371:Interferon-gamma; D020381:Interleukin-17; D007378:Interleukins; D000097043:Interleukin-22