Blog

17 new pubmed citations were retrieved for your search.
Click on the search hyperlink below to display the complete search results:

primary immunodeficiency NOT human immunodeficiency virus

These pubmed results were generated on 2020/12/15

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books.
Citations may include links to full-text content from PubMed Central and publisher web sites.

Powered by WPeMatico

Human T-bet Governs Innate and Innate-like Adaptive IFN-γ Immunity against Mycobacteria.

Cell. 2020 Dec 03;:

Authors: Yang R, Mele F, Worley L, Langlais D, Rosain J, Benhsaien I, Elarabi H, Croft CA, Doisne JM, Zhang P, Weisshaar M, Jarrossay D, Latorre D, Shen Y, Han J, Ogishi M, Gruber C, Markle J, Al Ali F, Rahman M, Khan T, Seeleuthner Y, Kerner G, Husquin LT, Maclsaac JL, Jeljeli M, Errami A, Ailal F, Kobor MS, Oleaga-Quintas C, Roynard M, Bourgey M, El Baghdadi J, Boisson-Dupuis S, Puel A, Batteux F, Rozenberg F, Marr N, Pan-Hammarström Q, Bogunovic D, Quintana-Murci L, Carroll T, Ma CS, Abel L, Bousfiha A, Di Santo JP, Glimcher LH, Gros P, Tangye SG, Sallusto F, Bustamante J, Casanova JL

Abstract
Inborn errors of human interferon gamma (IFN-γ) immunity underlie mycobacterial disease. We report a patient with mycobacterial disease due to inherited deficiency of the transcription factor T-bet. The patient has extremely low counts of circulating Mycobacterium-reactive natural killer (NK), invariant NKT (iNKT), mucosal-associated invariant T (MAIT), and Vδ2+ γδ T lymphocytes, and of Mycobacterium-non reactive classic TH1 lymphocytes, with the residual populations of these cells also producing abnormally small amounts of IFN-γ. Other lymphocyte subsets develop normally but produce low levels of IFN-γ, with the exception of CD8+ αβ T and non-classic CD4+ αβ TH1∗ lymphocytes, which produce IFN-γ normally in response to mycobacterial antigens. Human T-bet deficiency thus underlies mycobacterial disease by preventing the development of innate (NK) and innate-like adaptive lymphocytes (iNKT, MAIT, and Vδ2+ γδ T cells) and IFN-γ production by them, with mycobacterium-specific, IFN-γ-producing, purely adaptive CD8+ αβ T, and CD4+ αβ TH1∗ cells unable to compensate for this deficit.

PMID: 33296702 [PubMed – as supplied by publisher]

Powered by WPeMatico

Differently expressed microRNA in response to the first Ig replacement therapy in common variable immunodeficiency patients.

Sci Rep. 2020 Dec 08;10(1):21482

Authors: De Felice B, Nigro E, Polito R, Rossi FW, Pecoraro A, Spadaro G, Daniele A

Abstract
Common variable immunodeficiency (CVID) is a complex primary immunodeficiency disorder characterized by a high clinical and genetic heterogeneity. The molecular underlying causes of CVID are not still now clear and the delays in diagnosis and treatment worsen the prognosis of the patients. MicroRNAs are non-coding, endogenous small RNAs often deregulated in human diseases, such as autoimmune and other immune-based disorders. In the present study, we aimed to evaluate miRNAs associated with the CVID and, in particular, with the response to the first Ig replacement therapy. To this aim, we compared miRNA profile obtained by serum samples of treatment-naïve CVID patients before and 24 h after the first Ig replacement therapy. For the first time, using a microarray assay followed by an integrated bioinformatics/biostatistics analysis, we identified five microRNAs (hsa-miR-6742, hsa-miR-1825, hsa-miR-4769-3p, hsa-miR-1228-3p, hsa-miR-1972) differently modulated in CVID patients by Ig infusion. All of them were down-regulated, excepted miR-6742 which was up-regulated. The latter may be of particular interest, since its functions are related to pathways involving Class I MHC mediated antigen processing and adaptive as well as innate Immune System. In conclusion, this study shows for the first time the modulation of miRNAs involved in CVID patients after the first Ig replacement therapy. Further studies are needed to assess whether such miRNAs could represent novel potential biomarkers in management and therapy of CVID patients.

PMID: 33293557 [PubMed – in process]

Powered by WPeMatico

JAK inhibition in early onset somatic, nonclonal STAT5B gain-of-function disease.

J Allergy Clin Immunol Pract. 2020 Dec 05;:

Authors: Eisenberg R, Gans MD, Leahy TR, Gothe F, Perry C, Raffeld M, Eisenberg R, Gans MD, Leahy TR, Gothe F, Perry C, Raffeld M, Xi L, Blackstone S, Ma C, Hambleton S, Milner J

PMID: 33290916 [PubMed – as supplied by publisher]

Powered by WPeMatico

Primary gastroduodenal tuberculosis complicated with acute pancreatitis: a rare case report and literature review.

Eur J Med Res. 2020 Dec 07;25(1):65

Authors: Li Y, Liao S, Zuo H, Yang W, Jiang D

Abstract
BACKGROUND: Tuberculosis (TB) is a major health problem worldwide. Even in highly prevalent countries, primary gastroduodenal tuberculosis is a rare manifestation of extrapulmonary tuberculosis. In recent years, as the incidence of tuberculosis has increased year by year, the occur of gastroduodenal tuberculosis has also increased. Endoscopy is an important tool for diagnosing gastroduodenal tuberculosis. The performance of gastroduodenal tuberculosis under endoscopy is often non-specific, which may imitate other benign or malignant gastroduodenal diseases. Diagnosis of gastroduodenal tuberculosis relies on a combination of endoscopy and guided biopsy.
CASE PRESENTATION: Here, we report a rare and interesting case of gastroduodenal tuberculosis with acute pancreatitis. The case initially mimicked gastroduodenal ulcers in morphology and appeared in a middle-aged person with normal immunity but with prolonged fever and abdominal pain. The disease was diagnosed through endoscopy and guided biopsy, and it responded well to antituberculosis drugs.
CONCLUSIONS: Clinicians must remember that even in the absence of immunodeficiency, as in this case, tuberculosis can affect any part of the gastrointestinal tract.

PMID: 33287912 [PubMed – in process]

Powered by WPeMatico

T cell gene therapy to treat immunodeficiency.

Br J Haematol. 2020 Sep 10;:

Authors: Panchal N, Ghosh S, Booth C

Abstract
The application of therapeutic T cells for a number of conditions has been developed over the past few decades with notable successes including donor lymphocyte infusions, virus-specific T cells and more recently CAR-T cell therapy. Primary immunodeficiencies are monogenetic disorders leading to abnormal development or function of the immune system. Haematopoietic stem cell transplantation and, in specific candidate diseases, haematopoietic stem cell gene therapy has been the only definitive treatment option so far. However, autologous gene-modified T cell therapy may offer a potential cure in conditions primarily affecting the lymphoid compartment. In this review we will highlight several T cell gene addition or gene-editing approaches in different target diseases with a focus on what we have learnt from clinical experience and promising preclinical studies in primary immunodeficiencies. Functional T cells are required not only for normal immune responses to infection (affected in CD40 ligand deficiency), but also for immune regulation [disrupted in IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy, X-Linked) due to dysfunctional FOXP3 and CTLA4 deficiency] or cytotoxicity [defective in X-lymphoproliferative disease and familial haemophagocytic lymphohistiocytosis (HLH) syndromes]. In all these candidate diseases, restoration of T cell function by gene therapy could be of great value.

PMID: 33280098 [PubMed – as supplied by publisher]

Powered by WPeMatico

Allogeneic hematopoietic stem cell transplantation in adults with primary immunodeficiency.

Hematology Am Soc Hematol Educ Program. 2020 Dec 04;2020(1):649-660

Authors: Morris EC

Abstract
With recent advances in genetic sequencing and its widespread adoption for clinical diagnostics, the identification of a primary immunodeficiency (PID) as the underlying cause of diseases presenting to hematologists including refractory autoimmunity, cytopenias, immune dysregulation, and hematologic malignancy, is increasing, particularly in the adult population. Where the pathogenic genetic variants are restricted to the hematopoietic system, selected patients may benefit from allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although it is generally accepted that early allo-HSCT (ie, in infancy or childhood) for PID is preferable, this is not always possible. The clinical phenotype of non-severe combined immune deficiency forms of PID can be very heterogeneous, in part because of the high number of genetic and functional defects affecting T, B, and natural killer cells, neutrophils, and/or antigen presentation. As a result, some patients have less severe disease manifestations in childhood and/or a later de novo presentation. For others, a delayed diagnosis, lack of a genetic diagnosis, or a previous lack of a suitable donor has precluded prior allo-HSCT. Specific issues which make transplantation for adult PID patients particularly challenging are discussed, including understanding the natural history of rare diseases and predicting outcome with conservative management alone; indications for and optimal timing of transplant; donor selection; conditioning regimens; and PID-specific transplant management. The role of gene therapy approaches as an alternative to allo-HSCT in high-risk monogenic PID is also discussed.

PMID: 33275750 [PubMed – as supplied by publisher]

Powered by WPeMatico

Rituximab and eculizumab when treating nonmalignant hematologic disorders: infection risk, immunization recommendations, and antimicrobial prophylaxis needs.

Hematology Am Soc Hematol Educ Program. 2020 Dec 04;2020(1):312-318

Authors: Engel ER, Walter JE

Abstract
Rituximab and eculizumab, monoclonal antibodies that deplete most B cells and activate the terminal complement, respectively, are used to treat nonmalignant hematologic disorders (NMHDs), sometimes with unfavorable effects on the immune system. Hypogammaglobulinemia and neutropenia have been reported with variable prevalence in patients treated with rituximab. Neutropenia is mild and transient, and serious infectious complications are uncommon, so treatment is not indicated. Hypogammaglobulinemia is of greater concern. There is a lack of agreement on a standardized definition, and pre- and posttreatment immunoglobulin (Ig) levels are not routinely obtained. The association among low Ig levels, infectious risk, and mortality and morbidity in this population is unclear. There are also no formal guidelines on indication, risk factors, and threshold level of IgG to prompt Ig replacement therapy (IgRT). Among patients with NMHD, preexisting or persistent hypogammaglobulinemia (PH) after treatment with rituximab has been linked to underlying primary immunodeficiency disorders; therefore, a high index of suspicion should be maintained, and immunologic and genetic evaluation should be considered. Overall, important strategies in managing patients who are receiving rituximab include routine monitoring of pre- and posttreatment IgG levels, immune reconstitution (eg, B-cell subsets), assessment of vaccination status and optimization before treatment, and individualized consideration for IgRT. Accordingly, we discuss immunizations. Eculizumab, most commonly used in the treatment of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome, poses increased risk of meningococcal infections. To decrease the risk of infection, a meningococcal vaccination series is recommended before initiating therapy, and prophylactic antibiotics are preferred during the course of treatment.

PMID: 33275746 [PubMed – as supplied by publisher]

Powered by WPeMatico

Persistent Activation of Innate Immunity in Patients with Primary Antibody Deficiencies.

J Immunol Res. 2020;2020:8317671

Authors: Tsinti G, Makris D, Germenis AE, Speletas M

Abstract
Primary antibody deficiencies (PAD) represent a heterogeneous group of disorders, with common variable immunodeficiency being the most common with clinical significance. The main phenotypic defect resides in the inability of B cells to produce antibodies, and the cornerstone of therapy is immunoglobulin replacement treatment in order to fight infections. However, the management of the other inflammatory manifestations is inadequate, reinforcing the hypothesis that a complex genetic background affecting additional cell populations, such as polymorphonuclear cells (PMN) and monocytes, influences the expression of the clinical phenotype of the disease. In this study, we investigated by flow cytometry in different conditions (resting state, and after isolation and incubation, with and without stimuli) the expression pattern of several markers on PMN and monocytes, indicative of their maturation, capacity for chemotaxis, adhesion, opsonization, migration, and phagocytosis in 25 PAD patients, 12 healthy blood donors, and 4 septic patients. In this context, we also analyzed patients before and after the initiation of replacement treatment, as well as an untreated patient in different clinical conditions. Interestingly, we observed that PAD patients exhibit a chronic activation status of the innate immunity compartment, along with several differences in the expression of activation, maturation, and adhesion markers, with respect to different clinical conditions. Moreover, immunoglobulin replacement treatment had a favorable effect on PMN, as it was expressed by a more mature and less activated phenotype on basal state cells, and an enhanced activation capacity after LPS exposure. Thus, we conclude that PAD patients display a persistent innate immune cell activation, which is probably associated with the chronic inflammatory stress, usually observed in these disorders.

PMID: 33274244 [PubMed – in process]

Powered by WPeMatico