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Background: In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity., Objective: This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants., Methods: We identified 191 patients from 33 countries with 72 unique mutations. Inclusion criteria included symptoms of immune dysregulation and a biochemically confirmed germline heterozygous GOF variant in STAT3., Results: Overall survival was 88%, median age at onset of symptoms was 2.3 years, and median age at diagnosis was 12 years. Immune dysregulatory features were present in all patients: lymphoproliferation was the most common manifestation (73%); increased frequencies of double-negative (CD4-CD8-) T cells were found in 83% of patients tested. Autoimmune cytopenias were the second most common clinical manifestation (67%), followed by growth delay, enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, neurologic disease, vasculopathy, renal disease, and malignancy. Infections were reported in 72% of the cohort. A cellular and humoral immunodeficiency was observed in 37% and 51% of patients, respectively. Clinical symptoms dramatically improved in patients treated with JAK inhibitors, while a variety of other immunomodulatory treatment modalities were less efficacious. Thus far, 23 patients have undergone bone marrow transplantation, with a 62% survival rate., Conclusion: STAT3 GOF patients present with a wide array of immune-mediated disease including lymphoproliferation, autoimmune cytopenias, and multisystem autoimmunity. Patient care tends to be siloed, without a clear treatment strategy. Thus, early identification and prompt treatment implementation are lifesaving for STAT3 GOF syndrome., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Food protein-induced enterocolitis (FPIES) is a non-IgE cell- mediated food allergy that can be severe and lead to shock. Despite the potential seriousness of reactions, awareness of FPIES is low; high-quality studies providing insight into the pathophysiology, diagnosis, and management are lacking; and clinical outcomes are poorly established. This consensus document is the result of work done by an international workgroup convened through the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology and the International FPIES Association advocacy group. These are the first international evidence-based guidelines to improve the diagnosis and management of patients with FPIES. Research on prevalence, pathophysiology, diagnostic markers, and future treatments is necessary to improve the care of patients with FPIES. These guidelines will be updated periodically as more evidence becomes available., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

The atopic status of patients with leprosy was assessed by medical history, physical examination, serum total IgE, and specific IgE antibodies to common allergens (by skin testing and RAST). Tests for specific IgE antibody to Mycobacterium leprae were performed by RAST and immunoblotting technique. We studied 28 patients with leprosy and 49 control subjects. The two groups did not differ significantly in the prevalence of atopic disease. The IgE level was significantly higher in the patients, however, than in the control subjects, whether there was atopy (296.1 versus 96.3 IU/ml) or not atopy (72.9 versus 18.9 IU/ml). Neither RAST nor immunoblotting technique detected significant levels of IgE antibodies to M. leprae. Our data indicate that leprosy was associated with increased total IgE level, but clinical atopy in patients with leprosy was similar to that in control subjects. The observed IgE increase in patients with leprosy appears to be generally nonspecific.

Nineteen patients with heterophil-positive infectious mononucleosis were followed with serial blood sampling for an average of 14.6 mo. A preillness serum sample, obtained more than 2 mo before onset of illness, was available from 9 patients. A total of 141 samples were tested under identical conditions for total IgE levels by a paper-disc radioimmunoassay. Hematologic and serologic studies were also done. IgE changes showed a definite pattern, consisting of an elevation early in illness, rapidly followed by a significant drop reaching a nadir by the third month, then gradually returning to the preillness level (PIL) over a period of about a year. On the average, the peak was about 3 times the PIL, and the nadir about half the PIL. The IgE peak always coincided with the peak of atypical lymphocytes, and in no instance did it occur later than the peaks of other hematologic or serologic changes. No definite relationship was noted between IgE levels and the severity of illness. Heterophil-positive infectious mononucleosis is the first well-defined infectious disease found to be associated with such a pattern of IgE response.

We studied 19 young children (aged 15 to 39 months) who had had a systemic allergic reaction after imported fire ant (IFA) sting. Skin testing was performed with whole body extract (WBE) of both Solenopsis species; positive reactions to S. invicta was noted in 94% and to S. richteri in 100%. Serum was tested for total IgE level and for specific IgE antibodies by RAST with WBE and venom (V) of S. invicta. In vitro results were compared with those of 19 age and sex-matched atopic control subjects. The range of total serum IgE level was 31 to 1720 IU/ml (geometric mean 160 IU/ml), compared with 7.5 to 6756 IU/ml (geometric mean 85 IU/ml) in the control subjects. The difference between the two groups, however, was not statistically significant (p greater than 0.05). In the IFA-allergic group, the IFA WBE RAST mean binding was 13.5% (range 2.0% to 30.2%), and the IFA V RAST mean was 29.2% (range 7.8% to 46.7%). The control sera demonstrated low levels of activity to both IFA WBE RAST (0.7% to 4.8%) and IFA V RAST (0.7% to 5.9%). IFA WBE RAST demonstrated that 26% of the IFA-allergic patients had counts within the range of the atopic control subjects. In contrast, the IFA V RAST clearly separated all IFA-allergic patients from their age and sex-matched atopic control subjects. A scoring system for IFA V RAST is proposed. These results demonstrate superiority of IFA V over IFA WBE RAST in the diagnosis of allergy to S. invicta.