Patients with Chromosome 11q-abberations are Characterized by a Combined Primary Immunodeficiency Involving Both B- and T-lymphocytes

2021 ◽  
Author(s):  
Elisabeth Janneke Huisman ◽  
A. Rick Brooimans ◽  
Samone Mayer ◽  
Marieke Joosten ◽  
Louis de Bont ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
B Lymphocyte ◽  
Fungal Infections ◽  
Prophylactic Antibiotic ◽  
Tube Placement ◽  
Primary Immune Deficiency ◽  
Lymphocyte Function ◽  
Chromosome 11 ◽  
Infectious Burden ◽  
Tract Infections

Abstract Disorders of the long arm of chromosome 11 (11q) are rare and involve various chromosomal regions. Patients with 11q-disorders, including Jacobsen syndrome, often present with a susceptibility for bacterial, prolonged viral and fungal infections partially explained by hypogammaglobulinemia. Additional T-lymphocyte or granular neutrophil dysfunction may also be present. In order to evaluate infectious burden and immunological function in patients with 11q-disorders, we prospectively studied a cohort of 14 patients with various 11q aberrations. Clinically, 12 patients exhibited prolonged and repetitive respiratory tract infections, frequently requiring (prophylactic) antibiotic treatment (n=7), ear-tube placement (n=9) or use of inhalers (n=5). Complicated varicella infections (n=5), chronic eczema (n=6), warts and chronic fungal infections (n=4) were reported. Six patients were on immunoglobulin replacement therapy. We observed a high prevalence of low B-lymphocyte counts (n=8), decreased T-lymphocyte counts (n=5) and abnormal T-lymphocyte function (n=12). Granulocyte function was abnormal in 29% without an aberrant clinical phenotype. Immunodeficiency was found in patients with terminal and interstitial 11q-deletions and in one patient with 11q trisomy. Genetically, FLI1 and ETS1 are seen as causative for the immunodeficiency, but these genes were deleted nor duplicated in 5 of our 14 patients. Alternative candidate genes on 11q such as ATM, CD3-cluster, CBL and THYN1 may have a role in immune dysregulation in our patients. In conclusion, we present evidence that a combined primary immune deficiency may be present in patients with 11q-disorders leading to clinically relevant infections. Therefore, broad immunological screening and necessary treatment is of importance in this patient group.

scholarly journals Control of T lymphocyte fate decisions by PI3K signaling

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1171
Author(s):  
Benjamin Murter ◽  
Lawrence P. Kane
Keyword(s):  
Signaling Pathways ◽  
T Lymphocyte ◽  
Intracellular Signaling ◽  
B Lymphocyte ◽  
Lymphocyte Function ◽  
Antigen Receptors ◽  
Lipid Kinase ◽  
Cellular Processes ◽  
Intracellular Signaling Pathways ◽  
B Lymphocyte Development

Virtually all aspects of T and B lymphocyte development, homeostasis, activation, and effector function are impacted by the interaction of their clonally distributed antigen receptors with antigens encountered in their respective environments. Antigen receptors mediate their effects by modulating intracellular signaling pathways that ultimately impinge on the cytoskeleton, bioenergetic pathways, transcription, and translation. Although these signaling pathways are rather well described at this point, especially those steps that are most receptor-proximal, how such pathways contribute to more quantitative aspects of lymphocyte function is still being elucidated. One of the signaling pathways that appears to be involved in this “tuning” process is controlled by the lipid kinase PI3K. Here we review recent key findings regarding both the triggering/enhancement of PI3K signals (via BCAP and ICOS) as well as their regulation (via PIK3IP1 and PHLPP) and how these signals integrate and determine cellular processes. Lymphocytes display tremendous functional plasticity, adjusting their metabolism and gene expression programs to specific conditions depending on their tissue of residence and the nature of the infectious threat to which they are responding. We give an overview of recent findings that have contributed to this model, with a focus on T cells, including what has been learned from patients with gain-of-function mutations in PI3K as well as lessons from cancer immunotherapy approaches.

scholarly journals Good’s syndrome, a rare form of acquired immunodeficiency associated with thymomas

2019 ◽  
Vol 9 (2) ◽  
Author(s):  
Antonio Tamburello ◽  
Laura Castelnovo ◽  
Paola Faggioli ◽  
Daniela Bompane ◽  
Bruno Brando ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
B Lymphocyte ◽  
Fungal Infections ◽  
Early Recognition ◽  
Pneumocystis Jiroveci ◽  
Treatment Protocols ◽  
Gradual Improvement ◽  
Good’S Syndrome ◽  
Cold Sores ◽  
Tract Infections

Good’s syndrome (GS) or thymomaassociated immunodeficiency is a rare clinical entity that should be ruled out in patients with thymoma who develop severe, recurrent bacterial infections and opportunistic viral and fungal infections. There are no treatment protocols established, hence, early recognition is imperative to avoid complications. We report the case of a 42-year-old female, known for a previous thymectomy for giant thymoma who has suffered for a long time from recurrent pulmonary and urinary tract infections and cold sores. In March 2016 she referred to our unit complaining of fever, cough, chest pain, and cold sores due to Herpes simplex virus (HSV), confirmed serologically as HSV-1. Chest X-ray showed left pneumonia due to Streptococcus pneumoniae. She started antibiotics (amoxicillin/clavulanic acid associated with azithromycin) with gradual improvement. Given her history she was studied for an underlying immunodeficiency: IgG, IgA, and IgM were significantly low or absent, as well as all IgG subclasses; blood and bone marrow aspirate leucocyte immunophenotyping showed complete absence of B lymphocytes and reduced CD4+ T cells. In light of: i) thymoma; ii) B lymphocyte deficit; iii) hypogammaglobulinemia; iv) recurrent infections, GS was diagnosed and pre-emptive immunoglobulin treatment, associated with HSV and Pneumocystis jiroveci prophylaxis (Acyclovir for HSV and Sulfamethoxazole- Trimethoprim for P. jiroveci) were started. Since then the patient has no longer presented any infectious episodes.

scholarly journals T lymphocyte-dependent B lymphocyte proliferative response to antigen. I Genetic restriction of the stimulation of B lymphocyte proliferation.

1981 ◽  
Vol 153 (4) ◽  
pp. 871-882 ◽  
Author(s):  
H Y Tse ◽  
J J Mond ◽  
W E Paul
Keyword(s):  
T Lymphocytes ◽  
B Lymphocytes ◽  
T Lymphocyte ◽  
Lymphocyte Proliferation ◽  
B Lymphocyte ◽  
Antigen Specificity ◽  
Apparent Lack ◽  
The Face ◽  
Stimulation Of

For the purpose of examining more closely the interaction between T and B lymphocytes, we have developed an in vitro T lymphocyte-dependent B lymphocyte proliferation assay. Proliferation of B lymphocytes in response to antigen was found to depend on the presence of primed T lymphocytes; the B lymphocytes could be derived from nonprimed animals. It appears that these B cells were nonspecifically recruited to proliferate. This nonspecific recruitment, however, was found to be Ir-gene restricted in that B lymphocytes from B10.S mice, which are genetic nonresponders to the polymer Glu60-Ala30-Tyr10 (GAT), could not be stimulated by GAT-primed (responder X nonresponder) F1 T cells. The apparent lack of antigen specificity in the face of Ir gene-restricted T-B interaction may have important implications in our understanding of the recognition unit(s) on T lymphocytes.

scholarly journals CD4+ T Lymphocytes from Calves Immunized withAnaplasma marginale Major Surface Protein 1 (MSP1), a Heteromeric Complex of MSP1a and MSP1b, Preferentially Recognize the MSP1a Carboxyl Terminus That Is Conserved among Strains

2001 ◽  
Vol 69 (11) ◽  
pp. 6853-6862 ◽  
Author(s):  
Wendy C. Brown ◽  
Guy H. Palmer ◽  
Harris A. Lewin ◽  
Travis C. McGuire
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Protective Immunity ◽  
B Lymphocyte ◽  
Surface Protein ◽  
Specific Response ◽  
Major Surface Protein ◽  
Ifn Γ ◽  
Major Surface ◽  
Lymphocyte Responses

ABSTRACT Native major surface protein 1 (MSP1) of the ehrlichial pathogenAnaplasma marginale induces protective immunity in calves challenged with homologous and heterologous strains. MSP1 is a heteromeric complex of a single MSP1a protein covalently associated with MSP1b polypeptides, of which at least two (designated MSP1F1 and MSP1F3) in the Florida strain are expressed. Immunization with recombinant MSP1a and MSP1b alone or in combination fails to provide protection. The protective immunity in calves immunized with native MSP1 is associated with the development of opsonizing and neutralizing antibodies, but CD4+ T-lymphocyte responses have not been evaluated. CD4+ T lymphocytes participate in protective immunity to ehrlichial pathogens through production of gamma interferon (IFN-γ), which promotes switching to high-affinity immunoglobulin G (IgG) and activation of phagocytic cells to produce nitric oxide. Thus, an effective vaccine for A. marginaleand related organisms should contain both T- and B-lymphocyte epitopes that induce a strong memory response that can be recalled upon challenge with homologous and heterologous strains. This study was designed to determine the relative contributions of MSP1a and MSP1b proteins, which contain both variant and conserved amino acid sequences, in stimulating memory CD4+ T-lymphocyte responses in calves immunized with native MSP1. Peripheral blood mononuclear cells and CD4+ T-cell lines from MSP1-immunized calves proliferated vigorously in response to the immunizing strain (Florida) and heterologous strains of A. marginale. The conserved MSP1-specific response was preferentially directed to the carboxyl-terminal region of MSP1a, which stimulated high levels of IFN-γ production by CD4+ T cells. In contrast, there was either weak or no recognition of MSP1b proteins. Paradoxically, all calves developed high titers of IgG antibodies to both MSP1a and MSP1b polypeptides. These findings suggest that in calves immunized with MSP1 heteromeric complex, MSP1a-specific T lymphocytes may provide help to MSP1b-specific B lymphocytes. The data provide a basis for determining whether selected MSP1a CD4+ T-lymphocyte epitopes and selected MSP1a and MSP1b B-lymphocyte epitopes presented on the same molecule can stimulate a protective immune response.

Abstract 425: Lycopene Modulates T Lymphocyte Function by Modulating Th1 Responses and Treg Lymphocyte Population

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Lynsey M Mills ◽  
Heather Wilson ◽  
Frank Thies
Keyword(s):  
T Lymphocyte ◽  
T Regulatory Cells ◽  
Mononuclear Cells ◽  
T Cell Subsets ◽  
Lymphocyte Function ◽  
T Helper ◽  
T Helper 1 ◽  
Peripheral Blood Mononuclear ◽  
Lymphocyte Activity ◽  
Ifn Γ

Increased lycopene intake might have cardiovascular benefits, potentially through anti-inflammatory mechanisms. We recently showed that lycopene can influence lymphocyte activity by modulating processes involved in early cellular activation. T lymphocytes comprise different subsets, T cytotoxic, T helper 1 (Th1), T helper 2 (Th2) and T regulatory cells (Treg). We aimed to determine whether lycopene could specifically modulate T-cell subsets function and activity. Peripheral blood mononuclear cells from 11 healthy adults were cultured for 18hr to 60h in the presence of lycopene-enriched liposomes (0-1.18μg lycopene/ml) with or without mitogens. The secretion of cytokines representative of Th1,Th2 and Treg activities were measured by ELISA (IL-2, IL-1β, IL-10, IFN-γ and TGF-β) or cytometric bead array (IL-4, IL-10, IL17 and IFN-γ). The population profile of Tc (CD3+/CD8+), Th (CD3+/CD4+), Treg (CD4+/CD25+), and the Treg subsets nTreg (CD4+/CD25+/FoxP3+) and iTreg (CD4+/CD25+/IL-10+) was determined by flow cytometry. After 18h incubation, IL-2 concentration in the medium was significantly reduced (-29%, p=0.001) in the presence of lycopene (1.18μg/mL). Similar effects were observed after 36h and 60h culture for IFN-γ (-23%, p=0.015), Il-10 (-30%, p=0.023), IL-17 (-30%, p=0.019) but not IL-4 or TGF-β. The proportion of Treg cell was also significantly increased by 36% (p=0.001) in the presence of lycopene (1.18μg/mL) compared with non-treated activated cells. Furthermore, the proportions of iTreg cells were significantly increased by after incubation with lycopene while the proportion of nTreg cells decreased (-20.5 %, p=0.049). We conclude that increased lycopene intake may be beneficial against atherogenesis by modulating T lymphocyte function, particularly in relation toTh1 and Treg.

scholarly journals Pharmacovigilance of Sodium-Glucose Cotransporter-2 Inhibitors for Genital Fungal Infections and Urinary Tract Infections: A Review of the Food and Drug Administration Adverse Event Reporting System Database

2018 ◽  
Vol 34 (4) ◽  
pp. 144-148
Author(s):  
Hannah Mohammad ◽  
Nancy Borja-Hart
Keyword(s):  
Urinary Tract ◽  
Tract Infection ◽  
Adverse Events ◽  
Fungal Infections ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Sglt2 Inhibitors ◽  
Postmarketing Surveillance ◽  
Sodium Glucose Cotransporter ◽  
Tract Infections

Background: Postmarketing surveillance had previously identified the need for revisions in the labeling of the sodium-glucose cotransporter-2 (SGLT2) inhibitors drug class related to the risk of diabetic ketoacidosis. Other adverse events have been reported. Objective: To examine postmarketing surveillance data of the SGLT2 inhibitors, using the Food and Drug Administration Adverse Event Reporting System (FAERS) database, specifically to assess prevalence of urinary tract infections (UTIs) and genital fungal infections. Methods: FAERS case reports submitted between March 2013 and November 2015 were reviewed for 6 SGLT2 inhibitors (mono and combo therapies). The Medical Dictionary for Regulatory Activities (MedDRA) was used to define preferred terms (genital fungal infections: vulvovaginal mycotic infection, vulvovaginal candidiasis, urinary tract infection fungal, and genital candidiasis; UTI: urinary tract infection, genitourinary tract infection, kidney infection, cystitis, and pyelonephritis). Word frequencies were queried using the qualitative data analysis software NVivo 11 (QSR International), and results were then individually reviewed. Results: A total of 12 581 cases were received, but 466 were excluded (total n = 12 115). A total of 348 cases related to genital fungal infections were reported (2.9% of reports submitted): dapagliflozin = 53, empagliflozin/linagliptin = 6, canagliflozin = 267, canagliflozin/metformin = 3, empagliflozin = 17, and dapagliflozin/metformin HCl ER = 2. A total of 727 cases related to UTIs were reported (6% of reports submitted): dapagliflozin = 168, empagliflozin/linagliptin = 5, canagliflozin/metformin = 8, canagliflozin = 503, empagliflozin = 38, and dapagliflozin/metformin HCl ER = 5. Conclusions: A causal relationship between SGLT2 inhibitors and the adverse events reported cannot be established due to the nature of postmarketing surveillance. However, health care providers should counsel patients about these potential adverse events.

Perioperative Cefovecin to Reduce the Incidence of Urinary Tract Infection in Dogs Undergoing Hemilaminectomy

2016 ◽  
Vol 52 (5) ◽  
pp. 297-304 ◽  
Author(s):  
Joseph D. Palamara ◽  
Jennifer J. Bonczynski ◽  
Jason M. Berg ◽  
Philip J. Bergman
Keyword(s):  
Urinary Tract ◽  
Urine Culture ◽  
Prophylactic Antibiotic ◽  
Neurologic Deficit ◽  
Antibiotic Administration ◽  
Type I ◽  
Additional Risk ◽  
Neurologic Recovery ◽  
Tract Infections ◽  
Disc Extrusion

ABSTRACT The prevalence of urinary tract infections (UTIs) in dogs with Type I intervertebral disc extrusion has been reported as high as 38% within 6 wk of surgery. Proper treatment of a UTI is important with myelopathy because it is a risk factor for persistent infection and reinfection in dogs. The study authors' investigated the incidence of UTIs in dogs having received either cefovecin or cefazolin as a preoperative prophylactic antibiotic for thoracolumbar hemilaminectomy. Thirty-nine dogs were retrospectively identified and assigned to groups based on preoperative antibiotic administration and postoperative urinary tract management. Urinalysis and urine culture performed preoperatively, at 2 wk, and at 6 wk, were reviewed to determine the incidence of UTIs. Urinary tract management, grade of neurologic deficit, time to ambulation, and time to voluntary urination were identified to evaluate for additional risk factors. No significant prevalence of UTI incidence was appreciated between the cefovecin and cefazolin groups. Patients with higher grades of neurologic deficit and that took longer to regain ambulation and voluntary urination were at significantly greater risk for UTIs throughout the postoperative period. This study reemphasizes the importance of continued surveillance for UTIs in patients with prolonged neurologic recovery.

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