Dilara Fatma Kocacık Uygun

Clinical outcome in IL-10-and IL-10 receptor-deficient patients with or without hematopoietic stem cell transplantation

BACKGROUND Inherited deficiencies of IL-10 or IL-10 receptor (IL-10R) lead to immune dysregulation with life-threatening early-onset enterocolitis. OBJECTIVES We sought to gather clinical data of IL-10/IL-10R-deficient patients and devise guidelines for diagnosis and management, including hematopoietic stem cell transplantation (HSCT). METHODS We enrolled 40 patients with early-onset enterocolitis and screened for mutations in IL10/IL10R using genetic studies, functional studies, or both of the IL-10 signaling pathway. Medical records of IL-10/IL-10R-deficient patients were reviewed and compiled. RESULTS Of 40 patients, we identified 7 with novel mutations, predominantly in consanguineous families with more than 1 affected member. IL-10/IL-10R-deficient patients had intractable enterocolitis, perianal disease, and fistula formation. HSCT was carried out in 2 patients with IL-10 deficiency and 1 patient with IL-10R α chain deficiency and proved to be an effective therapy, leading to rapid improvement of clinical symptoms and quality of life. CONCLUSION Because the defect in patients with IL-10/IL-10R deficiency resides in hematopoietic lineage cells and their colitis is resistant to standard immunosuppressive therapy, HSCT should be considered early as a potentially curative therapeutic option.

Cutaneous Leukocytoclastic Vasculitis due to Salmonella enteritidis in a Child with Interleukin-12 Receptor Beta-1 Deficiency

Abstract:  Defects in the interleukin 12 (IL‐12)/interferon gamma (IFN‐γ) pathway result in Mendelian susceptibility to mycobacterial disease (MSMD). IL‐12 receptor beta 1 (IL‐12Rβ1) deficiency, the most common form of MSMD, is associated with weakly virulent mycobacteria and salmonella. Infections in patients with this deficiency are extraintestinal, or septicemic, recurrent infections with nontyphoid salmonellae. Here we report a case of an IL‐12Rβ1 deficiency with cutaneous leukocytoclastic vasculitis due to Salmonella enteritidis.

In vitro interferon γ improves the oxidative burst activity of neutrophils in patients with chronic granulomatous disease with a subtype of gp91phox deficiency.

Aim of this study Chronic granulomatous disease (CGD) is a genetically heterogeneous primary immunodeficiency caused by a defect in phagocyte production of oxygen metabolites, and resulting in infections produced by catalase-positive microorganisms and fungi. Interferon γ (IFN-γ) has a multitude of effects on the immune system. Although preliminary studies with CGD patients on treatment with IFN-γ showed that it enhanced phagocytosis and superoxide production, ongoing studies did not reveal a significant increase of this function. Here we investigated the oxidative capacity of phagocytes in different subtypes of CGD patients on treatment with IFN-γ in vitro. Material and methods Fifty-seven patients with CGD from 14 immunology centres were enrolled to our multi-centre study. Twenty-one patients were studied as controls. Oxidative burst assay with dihydrorhodamine 123 (DHR) was used and the stimulation index (SI) was calculated with respect to CGD subtypes in both neutrophils and monocytes before, and then one and 24 hours after adding IFN-γ. Results Upon comparison of the SIs of the patients’ neutrophils before in vitro IFN-γ at hour 0, and after adding IFN-γ at hour 1 and 24 were compared, and the differences were determined between hours 0-24 and hours 1-24. This difference was especially apparent between hours 1-24. In CGD subtypes, particularly in gp91phox subtype, it was seen that, following in vitro IFN-γ, SIs of neutrophils began to increase after hour 1, and that increase became more apparent at hour 24. Conclusions Our study showed that IFN-γ treatment may increase the oxidative bursting activity by increasing the superoxide production in neutrophils, particularly in gp91phox subtype.

Escherichia coli brain abscess in a twin pair associated with TLR4 gene mutation

Brain abscesses are uncommon complications of bacterial meningitis or sepsis in neonates and infants. The causative pathogens of brain abscess in newborns are various. Of those, Escherichia coli is rarely seen as a pathogen in brain abscess at this age. Herein we reported brain abscesses in twin infants caused by E. coli sepsis. Interestingly, genetic analysis identified heterozygous Toll‐like receptor 4 (TLR4) gene mutation in the twins. Because TLR plays an important role in the natural response to bacterial products and initiates specific immune response against these pathogens, this may explain the development of brain abscess in the present case.