STAT3 gain-of-function (GOF) mutations can be responsible for an incomplete phenotype mainly characterized by hematological autoimmunity, even in the absence of other organ autoimmunity, growth impairment, or severe infections. We hereby report a case with an incomplete form of STAT3 GOF intensified by a concomitant hereditary hematological disease, which misleads the diagnosis. The patient presented with lymphadenopathy, splenomegaly, hypogammaglobulinemia, and severe autoimmune hemolytic anemia (AIHA) with critical complications, including stroke. A Primary Immune Regulatory Disorders (PIRD) was suspected, and molecular analysis revealed a de novo STAT3 gain-of-function mutation. The response to multiple immune suppressive treatments was ineffective, and further investigations revealed a spectrin deficiency. Ultimately, hematopoietic stem cell transplantation from a matched unrelated donor was able to cure the patient. Our case shows an atypical presentation of STAT3 GOF associated with hereditary spherocytosis, and how achievement of a good long-term outcome depends on a strict clinical and laboratory monitoring, as well as on prompt therapeutic intervention.

No abstract

BackgroundNatural Killer cells (NKs) represent the innate counterpart of TCRαβ lymphocytes and are characterized by a high anti-tumor and an anti-viral cytotoxic activity. Recently, it has been demonstrated that NKs can express PD-1 as an additional inhibitory receptor. Specifically, PD-1 was identified on a subpopulation of terminally differentiated NKs from healthy adults with previous HCMV infection. So far it is unknown whether PD-1 appears during NK-cell development and whether this process is directly or indirectly related to HCMV infection.MethodsIn this study, we analyzed the expression and function of PD-1 on Cord Blood derived NKs (CB-NKs) on a large cohort of newborns through multiparametric cytofluorimetric analysis.ResultsWe identified PD-1 on CB-NKs in more than of half the newborns analyzed. PD-1 was present on CD56dim NKs, and particularly abundant on CD56neg NKs, but only rarely present on CD56bright NKs. Importantly, unlike in adult healthy donors, in CB-NKs PD-1 is co-expressed not only with KIR, but also with NKG2A. PD-1 expression was independent of HCMV mother seropositivity and occurs in the absence of HCMV infection/reactivation during pregnancy. Notably, PD-1 expressed on CB-NKs was functional and mediated negative signals when triggered.ConclusionTo our understanding, this study is the first to report PD-1 expression on CB derived NKs and its features in perinatal conditions. These data may prove important in selecting the most suitable CB derived NK cell population for the development of different immunotherapeutic treatments.

IntroductionAllergic reactions to insulin have become very rare with the introduction of human insulin. Anaphylaxis is a life-threatening condition that results from immediate IgE-mediated hypersensitivity. Desensitization to human insulin was reported to control immediate hypersensitivity reactions to insulin. Here, we describe the history and challenges of managing our patient and the development of an insulin desensitization protocol in a resource-limited setup.Case SummaryA 42-year-old Sudanese woman with poorly controlled type 2 diabetes on maximum antidiabetic medications required insulin therapy to achieve reasonable glycemic control. She developed progressive and severe immediate hypersensitivity reactions to insulin, including anaphylaxis. Serum sample analysis demonstrated insulin-specific IgE antibodies. The patient's poor glycemic control and the need for breast surgery indicated insulin desensitization. A 4-day desensitization protocol was delivered in an ICU bed for close observation. Following successful desensitization and 24-h observation, our patient was discharged on pre-meal human insulin, which was tolerated well to the current dateConclusionsAlthough insulin allergy is rare, once encountered, it is very challenging in patients who have no other treatment options available. Different protocols for insulin desensitization are described in the literature; the agreed protocol was implemented successfully in our patient despite the limited resources.