Die schmertzliche Toden-Grufft Des Wohl-Edlen/ Vest- und Hochgelahrten Herrn Christian Aland Knopfs/ Beyder Rechten wohlberühmten Doctoris, wie auch bey der hochflorirenden Stifft- und Handels-Stadt Naumburg wohlverdienten Bürgermeisters und ietziger Zeit gewesenen Stadt-Richters/ Als seines im Leben hochgeehrten Herrn Schwagers wolte am Tage der hochansehnlichen Beerdigung/ war der [ ] Octobr. 1696sten Jahres/ Mit diesen Jammer-Thränen einnetzen

DIE SCHMERTZLICHE TODEN-GRUFFT DES WOHL-EDLEN/ VEST- UND HOCHGELAHRTEN HERRN CHRISTIAN ALAND KNOPFS/ BEYDER RECHTEN WOHLBERÜHMTEN DOCTORIS, WIE AUCH BEY DER HOCHFLORIRENDEN STIFFT- UND HANDELS-STADT NAUMBURG WOHLVERDIENTEN BÜRGERMEISTERS UND IETZIGER ZEIT GEWESENEN STADT-RICHTERS/ ALS SEINES IM LEBEN HOCHGEEHRTEN HERRN SCHWAGERS WOLTE AM TAGE DER HOCHANSEHNLICHEN BEERDIGUNG/ WAR DER [ ] OCTOBR. 1696STEN JAHRES/ MIT DIESEN JAMMER-THRÄNEN EINNETZEN Die schmertzliche Toden-Grufft Des Wohl-Edlen/ Vest- und Hochgelahrten Herrn Christian Aland Knopfs/ Beyder Rechten wohlberühmten Doctoris, wie auch bey der hochflorirenden Stifft- und Handels-Stadt Naumburg wohlverdienten Bürgermeisters und ietziger Zeit gewesenen Stadt-Richters/ Als seines im Leben hochgeehrten Herrn Schwagers wolte am Tage der hochansehnlichen Beerdigung/ war der [ ] Octobr. 1696sten Jahres/ Mit diesen Jammer-Thränen einnetzen ([1]) Titelseite ([1]) Text ([1]

Early infant feeding and risk of developing islet autoimmunity and type 1 diabetes.

We investigated whether food supplementation within the first year life or age at introduction of gluten-containing foods influenced the risk of developing islet autoimmunity and type 1 diabetes. A total of 2,291 children with a family history of type 1 diabetes were prospectively followed from birth for 28,983 patient years (median 13.1 years). Dietary exposure data were collected by questionnaires, food records and by family interview. Exposure to gluten-containing foods before age 3 months, which occurred in 19 children, increased the risk of developing islet autoantibodies (n = 4), multiple islet autoantibodies (n = 4), and type 1 diabetes (n = 3) compared to exclusive breastfeeding within the first 3 months [adjusted hazard ratio (HR) 3.97 (95 % confidence interval 1.41-11.17), 5.39 (1.89-15.35), and 3.45 (1.04-11.48), respectively] and also compared to first exposure to gluten between 3.1 and 6.0 months of age [adjusted HR 3.40 (1.19-9.70), 4.25 (1.47-12.26), and 3.43 (1.01-11.66), respectively]. Children who received infant formula or other solid food within the first 3 months and children who received gluten-containing foods after age 6 months did not have an increased risk of islet autoantibodies, multiple islet autoantibodies or type 1 diabetes. Our present data affirm that compliance to infant feeding guidelines is a possible way to reduce type 1 diabetes risk in genetically susceptible children

Type 1 diabetes vaccine candidates promote human Foxp3⁺Treg induction in humanized mice.

Immune tolerance is executed partly by Foxp3(+)regulatory T (Treg) cells, which suppress autoreactive T cells. In autoimmune type 1 diabetes (T1D) impaired tolerance promotes destruction of insulin-producing β-cells. The development of autoantigen-specific vaccination strategies for Foxp3(+)Treg-induction and prevention of islet autoimmunity in patients is still in its infancy. Here, using human haematopoietic stem cell-engrafted NSG-HLA-DQ8 transgenic mice, we provide direct evidence for human autoantigen-specific Foxp3(+)Treg-induction in vivo. We identify HLA-DQ8-restricted insulin-specific CD4(+)T cells and demonstrate efficient human insulin-specific Foxp3(+)Treg-induction upon subimmunogenic vaccination with strong agonistic insulin mimetopes in vivo. Induced human Tregs are stable, show increased expression of Treg signature genes such as Foxp3, CTLA4, IL-2Rα and TIGIT and can efficiently suppress effector T cells. Such Foxp3(+)Treg-induction does not trigger any effector T cells. These T1D vaccine candidates could therefore represent an expedient improvement in the challenge to induce human Foxp3(+)Tregs and to develop novel precision medicines for prevention of islet autoimmunity in children at risk of T1D