No abstract

Mutations in STAT3 have recently been shown to cause autoimmune diseases through increased lymphoproliferation. We describe a novel Pro471Arg STAT3 mutation in a patient with multiple autoimmune diseases, causing hyperactivation of the Th17 pathway. We show that IL-17 production by primary T cells was enhanced and could not be further increased by IL-6, while IL-10 reduced Th17 cell numbers. Moreover, specific inhibition of STAT3 activation resulted in diminished IL-17 production. We show that the Pro471Arg STAT3 mutation yields both increased levels of IgA and IgG, probably due to high IL-21 levels. When remission was reached through medical intervention, IL-17 levels normalized and the clinical symptoms improved, supporting the idea that STAT3 gain-of-function mutations can cause hyperactivation of the Th17 pathway and thereby contribute to autoimmunity.

in some less diluted samples of the second test, raising the question whether a lower dilution (eg, 1:4) might be used to further improve the test sensitivity. A limitation of our study is the possibility that IgG 4 antibodiesnot measured in our samples-may have exerted competitive effects to IgE binding in our microarray. Also, the selected cutoff (ie, 0.03 ISU for diluted NasSec) cannot be automatically applied in other settings or to other microarrays. Large-scale studies are needed to confirm our promising findings. The technique should be investigated in more heterogeneous patient populations and with other airborne allergens. We thank Gabriele Holtappels (Upper Airway Research Laboratory, Ghent) for her advise on how to process NasSec and how to perform measurements in NasSec. We thank Alexander Rohrbach for his laboratory support (Charit e-Universit€ atsmedizin, Berlin). We thank Sander De Bruyne and Eveline van Mulders (2 medical students of Ghent University) for their help with patient recruitment and sample collection. Finally, we thank all patients for their participation in this study.

We here report an increased prevalence of gastrointestinal viruses and gastrointestinal complaints in antibody deficient patients. Patients that tested positive for gastrointestinal viruses showed diminished serum- and secretory IgA levels, and only in patients, virus positivity was associated with signs of mucosal inflammation. These findings suggest that particularly patients with low IgA are at risk for longstanding replication of gastrointestinal viruses, which may eventually result in CVID-related enteropathy.