Browsing by Subject "immune dysregulation"

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  • Garn, Holger; Bahn, Sabine; Baune, Bernhard T.; Binder, Elisabeth B.; Bisgaard, Hans; Chatila, Talal A.; Chavakis, Triantafyllos; Culmsee, Carsten; Dannlowski, Udo; Gay, Steffen; Gern, James; Haahtela, Tari; Kircher, Tilo; Mueller-Ladner, Ulf; Neurath, Markus F.; Preissner, Klaus T.; Reinhardt, Christoph; Rook, Graham; Russell, Shannon; Schmeck, Bernd; Stappenbeck, Thaddeus; Steinhoff, Ulrich; van Os, Jim; Weiss, Scott; Zemlin, Michael; Renz, Harald (2016)
    Recent research indicates that chronic inflammatory diseases, including allergies and autoimmune and neuropsychiatric diseases, share common pathways of cellular and molecular dysregulation. It was the aim of the International von-Behring-Rontgen Symposium (October 16-18, 2014, in Marburg, Germany) to discuss recent developments in this field. These include a concept of biodiversity; the contribution of urbanization, lifestyle factors, and nutrition (eg, vitamin D); and new mechanisms of metabolic and immune dysregulation, such as extracellular and intracellular RNAs and cellular and mitochondrial stress. Epigenetic mechanisms contribute further to altered gene expression and therefore to the development of chronic inflammation. These novel findings provide the foundation for further development of preventive and therapeutic strategies.
  • Hetemäki, Iivo; Jian, Ching; Laakso, Saila Marita; Mäkitie, Outi; Pajari, Anne-Maria; Vos de, Willem Meindert; Arstila, Petteri; Salonen, Anne (2021)
    Backgrounds and Aims: APECED is a rare autoimmune disease caused by mutations in the Autoimmune Regulator gene. A significant proportion of patients also have gastrointestinal symptoms, including malabsorption, chronic diarrhea, and obstipation. The pathological background of the gastrointestinal symptoms remains incompletely understood and involves multiple factors, with autoimmunity being the most common underlying cause. Patients with APECED have increased immune responses against gut commensals. Our objective was to evaluate whether the intestinal microbiota composition, predicted functions or fungal abundance differ between Finnish patients with APECED and healthy controls, and whether these associate to the patients’ clinical phenotype and gastrointestinal symptoms. Methods: DNA was isolated from fecal samples from 15 patients with APECED (median age 46.4 years) together with 15 samples from body mass index matched healthy controls. DNA samples were subjected to analysis of the gut microbiota using 16S rRNA gene amplicon sequencing, imputed metagenomics using the PICRUSt2 algorithm, and quantitative PCR for fungi. Extensive correlations of the microbiota with patient characteristics were determined. Results: Analysis of gut microbiota indicated that both alpha- and beta-diversity were altered in patients with APECED compared to healthy controls. The fraction of Faecalibacterium was reduced in patients with APECED while that of Atopobium spp. and several gram-negative genera previously implicated in biofilm formation, e.g. Veillonella, Prevotella, Megasphaera and Heamophilus, were increased in parallel to lipopolysaccharide (LPS) synthesis in imputed metagenomics. The differences in gut microbiota were linked to patient characteristics, especially the presence of anti-Saccharomyces cerevisiae antibodies (ASCA) and severity of gastrointestinal symptoms. Conclusions: Gut microbiota of patients with APECED is altered and enriched with predominantly gram-negative bacterial taxa that may promote biofilm formation and lead to increased exposure to LPS in the patients. The most pronounced alterations in the microbiota were associated with more severe gastrointestinal symptoms.
  • Tesch, Victoria Katharina; Abolhassani, Hassan; Shadur, Bella; Zobel, Joachim; Mareika, Yuliya; Sharapova, Svetlana; Karakoc-Aydiner, Elif; Rivière, Jacques G.; Garcia-Prat, Marina; Moes, Nicolette; Haerynck, Filomeen; Gonzales-Granado, Luis I.; Santos Pérez, Juan Luis; Mukhina, Anna; Shcherbina, Anna; Aghamohammadi, Asghar; Hammarström, Lennart; Dogu, Figen; Haskologlu, Sule; İkincioğulları, Aydan İ.; Köstel Bal, Sevgi; Baris, Safa; Kilic, Sara Sebnem; Karaca, Neslihan Edeer; Kutukculer, Necil; Girschick, Hermann; Kolios, Antonios; Keles, Sevgi; Uygun, Vedat; Stepensky, Polina; Worth, Austen; van Montfrans, Joris M.; Peters, Anke M.J.; Meyts, Isabelle; Adeli, Mehdi; Marzollo, Antonio; Padem, Nurcicek; Khojah, Amer M.; Chavoshzadeh, Zahra; Avbelj Stefanija, Magdalena; Bakhtiar, Shahrzad; Florkin, Benoit; Meeths, Marie; Gamez, Laura; Grimbacher, Bodo; Seppänen, Mikko R.J.; Lankester, Arjan; Gennery, Andrew R.; Seidel, Markus G. (2020)
    Background Recent findings strongly support hematopoietic stem cell transplantation (HSCT) in patients with severe presentation of LPS-responsive beige-like anchor protein (LRBA) deficiency, but long-term follow-up and survival data beyond previous patient reports or meta-reviews are scarce for those patients who do not receive a transplant. Objective This international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant. Method We assessed disease burden and treatment responses with a specially developed immune deficiency and dysregulation activity score, reflecting the sum and severity of organ involvement and infections, days of hospitalization, supportive care requirements, and performance indices. Results Of 76 patients with LRBA deficiency from 29 centers (median follow-up, 10 years; range, 1-52), 24 underwent HSCT from 2005 to 2019. The overall survival rate after HSCT (median follow-up, 20 months) was 70.8% (17 of 24 patients); all deaths were due to nonspecific, early, transplant-related mortality. Currently, 82.7% of patients who did not receive a transplant (43 of 52; age range, 3-69 years) are alive. Of 17 HSCT survivors, 7 are in complete remission and 5 are in good partial remission without treatment (together, 12 of 17 [70.6%]). In contrast, only 5 of 43 patients who did not receive a transplant (11.6%) are without immunosuppression. Immune deficiency and dysregulation activity scores were significantly lower in patients who survived HSCT than in those receiving conventional treatment (P = .005) or in patients who received abatacept or sirolimus as compared with other therapies, and in patients with residual LRBA expression. Higher disease burden, longer duration before HSCT, and lung involvement were associated with poor outcome. Conclusion The lifelong disease activity, implying a need for immunosuppression and risk of malignancy, must be weighed against the risks of HSCT.
  • Tangye, Stuart G.; Al-Herz, Waleed; Bousfiha, Aziz; Cunningham-Rundles, Charlotte; Franco, Jose Luis; Holland, Steven M.; Klein, Christoph; Morio, Tomohiro; Oksenhendler, Eric; Picard, Capucine; Puel, Anne; Puck, Jennifer; Seppänen, Mikko R. J.; Somech, Raz; Su, Helen C.; Sullivan, Kathleen E.; Torgerson, Troy R.; Meyts, Isabelle (2021)
    The most recent updated classification of inborn errors of immunity/primary immunodeficiencies, compiled by the International Union of Immunological Societies Expert Committee, was published in January 2020. Within days of completing this report, it was already out of date, evidenced by the frequent publication of genetic variants proposed to cause novel inborn errors of immunity. As the next formal report from the IUIS Expert Committee will not be published until 2022, we felt it important to provide the community with a brief update of recent contributions to the field of inborn errors of immunity. Herein, we highlight studies that have identified 26 additional monogenic gene defects that reach the threshold to represent novel causes of immune defects.