Purpose: The interleukin-7 receptor (IL-7R) is primarily expressed on lymphoid cells and plays a crucial role in the development, proliferation, and survival of T cells. Autosomal recessive mutations that disrupt IL-7Rα chain expression give rise to a severe combined immunodeficiency (SCID), which is characterized by lymphopenia and a TBNK phenotype. The objective here was to diagnose two siblings displaying the TBNK SCID phenotype as initial clinical genetic testing did not detect any variants in known SCID genes.
View Article and Find Full Text PDFAsthma and obesity are two of the most common chronic conditions in children and adolescents. There is increasing evidence that sphingolipid metabolism is altered in childhood asthma and is linked to airway hyperreactivity. Dysregulated sphingolipid metabolism is also reported in obesity.
View Article and Find Full Text PDFBackground: Allergic disorders are the consequence of IgE sensitization to allergens. Population studies have shown that certain human leukocyte antigen (HLA) alleles are associated with increased or decreased risk of developing allergy.
Objective: We aimed to characterize the relationship between HLA class II allelic diversity and IgE sensitization in an understudied Arab population.
Background: Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease characterized by defective signaling, which results in chronic, nonmalignant lymphoproliferation and autoimmunity accompanied by increased numbers of "double-negative" T-cells (DNTs) (T-cell receptor αβ+ CD4-CD8-) and an increased risk of developing malignancies later in life.
Case Presentation: We herein report a case of a newborn boy with a novel germline homozygous variant identified in the gene, exon 9, c.775del, which was considered pathogenic.
Allergy Rhinol (Providence)
December 2022
Background: Chronic spontaneous urticaria (CSU) can be extremely debilitating to the patient and challenging for the treating clinician. The National Institute of Health and Clinical Excellence (NICE) in the United Kingdom (UK) recommendation of omalizumab for patients who fail to respond to high-dose anti-histamines has improved treatment options and quality of life. However, there is still lack of clear guidelines for treatment of patients resistant to standard and anti-IgE therapies.
View Article and Find Full Text PDFBackground: Toll-like receptors (TLRs) mediate functions for host defense and inflammatory responses. TLR4 recognizes LPS, a component of gram-negative bacteria as well as host-derived endogenous ligands such as S100A8 and S100A9 proteins.
Objective: We sought to report phenotype and cellular function of individuals with complete TLR4 deficiency.
Purpose: Human serine/threonine kinase 4 (STK4) deficiency is a rare, autosomal recessive genetic disorder leading to combined immunodeficiency; however, the extent to which immune signaling and host defense are impaired is unclear. We assessed the functional consequences of a novel, homozygous nonsense STK4 mutation (NM_006282.2:c.
View Article and Find Full Text PDFTranscriptome profiling approaches have been widely used to investigate the mechanisms underlying psoriasis pathogenesis. Most researchers have measured changes in transcript abundance in skin biopsies; relatively few have examined transcriptome changes in the blood. Although less relevant to the study of psoriasis pathogenesis, blood transcriptome profiles can be readily compared across various diseases.
View Article and Find Full Text PDFInt J Gen Med
October 2020
Approximately 70% of all healthcare decisions affecting diagnosis and treatment involve the use of tests performed within pathology laboratories. The utilisation of diagnostic laboratory services continues to increase, with growth both in volume of tests requested, as well as in the breadth of test repertoire. Every year in the United Kingdom, approximately 1 billion tests are run in hospital laboratories, equivalent to 14 tests per person.
View Article and Find Full Text PDFThe majority of medical students and many physicians find basic science immunology confusing and the teaching of immunology to be uninteresting. Physicians undergoing training in a range of disciplines treat patients with immunological disease, including allergy/immunology and rheumatology. It is essential for senior medical students and physicians to understand the pathology of immune diseases and the pharmacology of immune interventions.
View Article and Find Full Text PDFThis is a series of 4 cases (3 therapeutic failure and 1 early relapse) in adult patients treated with allergen immunotherapy (AIT) for allergic rhinitis (AR) in our immunotherapy clinic, which treats 110 new patients per year. AIT includes both subcutaneous and sublingual routes. The current national/international AIT recommendations and the literature have been searched to identify guidance for the optimal management of therapeutic failure of AIT in AR.
View Article and Find Full Text PDFBMC Infect Dis
March 2020
Background: Infections with multidrug-resistant organisms (MDRO) pose a serious threat to patients with dysregulated immunity such as in hemophagocytic lymphohistiocytosis (HLH), but such infections have rarely been comprehensively characterized. Here, we present a fatal case of HLH secondary to cytomegalovirus (CMV) infection complicated by both anti-viral drug resistance and sepsis from multiple MDROs including pandrug-resistant superbug bacteria.
Case Presentation: A previously healthy, six-year-old boy presented with a 45-day history of fever prior to a diagnosis of hemophagocytic lymphohistiocytosis and hemorrhagic colitis, both associated with CMV.
B-cell targeted therapies (BCTT) are now widely used in autoimmune rheumatic diseases, including SLE, antineutrophil cytoplasmic antibody-associated vasculitis and rheumatoid arthritis. Early studies suggested that rituximab did not influence serum immunoglobulins. However, subsequently, with increased patient numbers, longer follow-up duration and many patients having received multiple BCTT courses, multiple subsequent studies have identified hypogammaglobulinaemia as a potential side effect.
View Article and Find Full Text PDFBackground: Consensus guidelines are not available for the use of immunoglobulin replacement therapy (IGRT) in patients developing iatrogenic secondary antibody deficiency following B-cell targeted therapy (BCTT) in autoimmune rheumatic disease.
Objectives: To evaluate the role of IGRT to manage hypogammaglobulinemia following BCTT in autoimmune rheumatic disease (AIRD).
Methods: Using an agreed search string we performed a systematic literature search on Medline with Pubmed as vendor.
Objectives: The association of B cell targeted therapies with development of hypogammaglobulinaemia and infection is increasingly recognized. Our aim was to develop consensus recommendations for immunoglobulin replacement therapy for management of hypogammaglobulinaemia following B cell targeted therapies in autoimmune rheumatic diseases.
Methods: A modified Delphi exercise involved a 17-member Taskforce committee, consisting of immunologists, rheumatologists, nephrologists, haematologists, a gastroenterologist, an immunology specialist nurse and a patient representative.
Clin Med (Lond)
December 2016
Drug allergy is defined as an adverse drug reaction with an established immunological mechanism. The National Institute for Health and Care Excellence published clinical guidelines on drug allergy in 2014 and quality standards in 2015. The intention of this article is to highlight indications for referral to specialists for management of drug allergy.
View Article and Find Full Text PDFSystemic lupus erythematosus (SLE) is a systemic autoimmune disease characterised by abnormal autoantibody production and clearance. This immunological background has been suggested to play a role in the susceptibility of SLE patients to infection. Moreover, drugs (most of them immunosuppressive or immunomodulating agents) used in the treatment of moderate and severe lupus give rise to a tendency for infections, including opportunistic ones.
View Article and Find Full Text PDFNephrol Dial Transplant
October 2011
Cytokines play an important role in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis. This is currently a very active area of research. Of particular interest is the use of cytokines as biomarkers of disease activity in SLE and lupus nephritis.
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