Epstein–Barr Virus and Treatment of Its Infection
Satya Prakash Gupta in Cancer-Causing Viruses and Their Inhibitors, 2014
X-linked lymphoproliferative syndrome (X-LPS) is characterized by three major phenotypes: (a) fatal IM, (b) B-cell lymphomas, and (c) dysgammaglobulinemia. Most of these lymphomas are Burkitt’s type (Skare et al. 1987). X-LPS is caused by hereditary mutations in the gene encoding the signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) on q25 position of X-chromosomes. The SLAM molecules are present on the surface of B- and T-lymphocytes; these initiate immune system related signal transduction pathways. SAP is present only on T-lymphocytes, and it acts as a negative regulator of SLAM molecules. Abnormality in SAP protein therefore produces extensive overreaction of T-lymphocytes during primary EBV infection that leads to fatal IM followed by virus-associated hematophagocytic syndrome (Latour et al. 2001). This syndrome destroys bone marrow and liver. Seventy percent of patients generally die within a few weeks; whereas 100% of patients die by the age of 40 due to hepatic necrosis and bone marrow failure. The only curative treatment for this syndrome is allogeneic bone marrow transplantation.
B Cells and Humoral Immunity
Constantin A. Bona, Francisco A. Bonilla in Textbook of Immunology, 2019
In these diseases, called dysgammaglobulinemias, absence or low levels of one or more Ig classes or subclasses results in variable immunodeficiency. The most common dysgammaglobulinemia is IgA deficiency. The estimated frequency is approximately 1:6–700 healthy blood donors. Thus, IgA deficiency (1–3% of the normal serum level) is most often asymptomatic. Usually both IgA isotypes (IgAl and IgA2) are absent, but selective deficiency of one IgA isotype has been observed. The serum level of other isotypes is most often normal, but a significant fraction of individuals will have associated deficiencies of IgG2 and IgG4 and/or IgE (associated IgG 1 or IgG3 deficiency is rare). (An) unidentified gene(s) located in the class III region of the major histocompatibility locus are important in some cases, although probably in conjunction with environmental factors (such as viral infections) and genes at other loci. Like common variable immunodeficiency, IgA deficiency may arise from any lesion affecting the selective induction of IgA production by B cells. There is only a single report of IgA deficiency as a result of a deletion involving Cα1. One case has been reported in which the patient was unable to synthesize secretory component and could not produce secretory IgA. This individual presented with chronic intestinal candidiasis.
Primary Immunodeficiencies
Gérard Chaouat in The Immunology of the Fetus, 2020
This syndrome, also called Type I dysgammaglobulinemia, can be inherited as an X-linked disease or according to an autosomal recessive inheritance. It is also described as an acquired syndrome, for instance following rubella fetopathy. The physiopathology of this B-cell ID is unknown. There is an apparent IgM switch defect, since patients’ B-lymphocytes do not produce other immunoglobulin isotypes than IgM. The question remains as to whether the disease is a primary B-cell defect or abnormal B-cell function secondary to a cell defect. Recently, Mayer et al. have shown that products from a T-cell line can induce patients’ B-cells to produce IgG and IgA, suggesting a primary T-cell defect.15 If confirmed, these data are of major importance, since they will definitively prove that the switch of IgM to other isotypes is T-cell dependent.
Very-Early Onset Chronic Active Colitis with Heterozygous Variants in LRBA1 and CARD11, a Case of “Immune TOR-Opathies”
Published in Fetal and Pediatric Pathology, 2023
Mai He, Amanda Wong, Kimberly Sutton, Mercia Jeanne Bezerra Gondim, Charles Samson
Decreased CTLA4 protein levels were observed within regulatory and conventional T cells isolated from LRBA-deficient patients compared those seen in analogous T cells from healthy controls. In the same study, abatacept, a CTLA-4-immunoglobulin fusion protein that mimics the biologic function of CTLA-4, ameliorated symptoms in a cohort of nine patients with novel biallelic loss-of-function mutations in LRBA [10]. A wide spectrum of clinical phenotypes has been reported for patients with homozygous or compound heterozygous mutations in LRBA. In a cohort of 22 patients with biallelic mutations in LRBA, a wide range of clinical manifestations was seen: immune dysregulation (seen in 95% of patients), organomegaly (86%), recurrent infections (71%), enteropathy (62%), and hypo/dysgammaglobulinemia (71) [14]. The vast majority of patients showed a reduction in regulatory T cells and multiple B-cell subsets (non-switched memory B cells, switched memory B cells, and plasmablasts). LRBA deficiency is associated with impaired mTOR/S6K Signaling in T Cells [6]. Targeted therapy for LRBA deficiency includes CTLA-Fc fusion protein (abatacept) and hydroxychloquine [15]. It was not surprising that a mTOR inhibitor (sirolimus) was a targeted therapy for LRBA deficiency [15],
Related Knowledge Centers
- Gamma Globulin
- Hypogammaglobulinemia
- Immunoglobulin M
- Immune Disorder
- Hyper Igm Syndrome
- Immunodeficiency