Monoallelic mutations in STAT1 are associated with a myriad of clinical phenotypes. Some clinical patterns appear to be preferentially associated with mutations in various STAT1 domains. Included are trends of phenotype-genotype correlations in patients with mutations in STAT1.

The mammalian gut is the richest immune organ in the body and serves as a central location for immune system development, processing, and education. Inflammatory bowel diseases (IBD) provide excellent models for studying both innate and adaptive responses to gut microbes and the host-immune system – microbe interactions in the gut. Microbes are linked to almost all of the known disease-associated genetic polymorphisms in IBD and are critical mediators of environmental effects (through food, hygiene, and infection). Human and animal-based research supports the central role of microbes in IBD pathogenesis at multiple levels. Animal models of IBD only develop in the presence of microbes, and co-housing mice that are genetically susceptible to gut inflammation with normal mice can lead to the development of bowel injury. Recent advances in research technologies, such as deep-sequencing that enables detailed compositional analyses, have revolutionized the study of host–microbe interactions in the gut; however, knowing which bacteria are present in the bowel is likely not sufficient. The function of the microbiota as a community is recognized as a critical factor for gut homeostasis. Animal models of IBD have provided critical insight into basic biology and disease pathogenesis, especially regarding the role of microbes in IBD pathogenesis. Although many of these recent discoveries on host–microbe interactions are not yet applied to patient care, these basic observations will certainly revolutionize patient care in the future. Using such data, we may be able to predict risk of disease, define biological subtypes, establish tools for prevention, and even cure IBD using microbes or their products. A broad spectrum of therapeutic tools spanning from fecal transplantation, probiotics, prebiotics, and microbial products to microbe-tailored diets may supplement current IBD treatments.

Mutations in IL-10R1, IL-10R2, and IL-10 have been identified in infants with severe colitis. The only possible hope for cure in these conditions is a hematopoietic stem cell transplantation (HSCT). We report here on a patient with IL-10R1 deficiency who suffered severe colitis and arthritis. She received a HSCT from a matched unrelated donor and her post-transplant course was uneventful. She has fully engrafted and her immune reconstitution was complete and robust. Although signs of colitis were completely resolved, arthritis was not reversed by HSCT. She continues to have joint swelling in the knees and inflammatory changes in the wrists. In conclusion, HSCT seems to have reversed colitis, but was insufficient to improve arthritis and possibly other autoimmune manifestations. Statement of novelty: This report describes a successful HSCT in severe infantile colitis caused by mutations in IL-10R1. Yet, the arthritis remains active, suggesting that conditions such as severe rheumatic disorders in childhood may not be reversed by replacement of the hematopoietic system.

Monoallelic mutations in STAT1 are associated with a variety of clinical patterns. We studied patients with novel mutations in the coiled-coil domain of STAT1. We found that clinical manifestations can vary from mild Candida infections limited to the oropharyx to serious serial strokes and skin cancer. Autoimmune manifestations were found to be rare and limited to hypothyroidism. Immune evaluations were normal or near normal in all patients with the exception of anergy to Candida. Mutation in the coiled-coil domain results in susceptibility to mucus membrane candidiasis as well as brain vascular anomalies. Statement of novelty: We describe novel mutations in the coiled-coil domain of STAT1.

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by defects in any of the subunits of nicotinamide adenine dinucleotide phosphate oxidase complex, required for proper phagocyte killing of bacteria and fungi. Most of the cases are X-linked, but autosomal recessive cases have also been identified. Patients suffer from recurrent, life-threatening infections and granulomatous inflammation of the skin, lymph nodes, lungs, liver, spleen, brain, and bones. CGD can be cured by hematopoietic stem cell transplantation. Imaging studies such as radiography, ultrasound, computed tomography, and magnetic resonance imaging play a key role in identifying the changes driven by both infection and dysregulated inflammation. These studies are critical for guiding management of this disorder. We present the most illustrative images from 7 patients with CGD. Statement of novelty: Imaging studies are highly useful for diagnosis, treatment, and follow-up of patients with CGD. We present images from children with CGD that manifested their disease in different organs and tissues, illustrating the typical location of infections and dysregulated inflammation in these types of patients.