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© Service photographie
Vue sur les capillaires d'un séquenceur d'ADN de la Plate Forme Génomique.
Publication : The Journal of allergy and clinical immunology

Role of the IL-12/IL-35 balance in patients with Sjögren syndrome

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in The Journal of allergy and clinical immunology - 12 Sep 2017

Fogel O, Rivière E, Seror R, Nocturne G, Boudaoud S, Ly B, Gottenberg JE, Le Guern V, Dubost JJ, Nititham J, Taylor KE, Chanson P, Dieudé P, Criswell LA, Jagla B, Thai A, Mingueneau M, Mariette X, Miceli-Richard C

Link to Pubmed [PMID] – 28916184

J. Allergy Clin. Immunol. 2018 Jul;142(1):258-268.e5

BACKGROUND: An interferon signature is involved in the pathogenesis of primary Sjögren syndrome (pSS), but whether the signature is type 1 or type 2 remains controversial. Mouse models and genetic studies suggest the involvement of T1 and type 2 interferon pathways. Likewise, polymorphisms of the IL-12A gene (IL12A), which encodes for IL-12p35, have been associated with pSS. The IL-12p35 subunit is shared by 2 heterodimers: IL-12 and IL-35.

OBJECTIVE: We sought to confirm genetic association of the IL12A polymorphism and pSS and elucidate involvement of the IL-12/IL-35 balance in patients with pSS by using functional studies.

METHODS: The genetic study involved 673 patients with pSS from 2 French pSS cohorts and 585 healthy French control subjects. Functional studies were performed on sorted monocytes, irrespective of whether they were stimulated. IL12A mRNA expression and IL-12 and IL-35 protein levels were assessed by using quantitative RT-PCR and ELISA and a multiplex kit for IL-35 and IL-12, respectively.

RESULTS: We confirmed association of the IL12A rs485497 polymorphism and pSS and found an increased serum protein level of IL-12p70 in patients with pSS carrying the risk allele (P = .016). Serum levels of IL-12p70 were greater in patients than control subjects (P = .0001), especially in patients with more active disease (P = .05); conversely, IL-35 levels were decreased in patients (P = .0001), especially in patients with more active disease (P = .05). In blood cellular subsets both IL12p35 and EBV-induced gene protein 3 (EBI3) mRNAs were detected only in B cells, with a trend toward a lower level among patients with pSS.

CONCLUSION: Our findings emphasize involvement of the IL-12/IL-35 balance in the pathogenesis of pSS. Serum IL-35 levels were associated with low disease activity, in contrast with serum IL-12p70 levels, which were associated with more active disease.

https://www.ncbi.nlm.nih.gov/pubmed/28916184