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Tumors of the Nervous System
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Predisposing factors include: Immunosuppression, inherited or acquired.Congenital immunodeficiencies.Combined immunodeficiency syndrome.Immunodeficiency associated with systemic lupus erythematosus, rheumatoid arthritis, and organ transplant recipients.Long-term corticosteroid treatment.Immunosuppression related to HIV infection.HIV or other viruses (Epstein–Barr virus [EBV]), growth factors, aberrant oncogene or tumor suppressor gene expression, and factors that promote genetic instability or DNA damage or alter host or viral genome repair may all promote cell hyperproliferation and clonal expansion.Hyperactivation of B cells is believed to contribute to lymphoma development associated with HIV infection.
The Severe Combined Immunodeficiency (scid) Mutation, Chromosome 16
Published in John P. Sundberg, Handbook of Mouse Mutations with Skin and Hair Abnormalities, 2020
John P. Sundberg, Leonard D. Shultz
Severe combined immunodeficiency occurs in humans as an autosomal recessive trait3,4 or X-linked characteristic4 that is clinically very similar to the mouse scid mutation. Recently, Schwartz et al.19 described five human patients with impaired rearrangement processes at the JH region analogous to the defect in scid/scid mice. Human severe combined immune deficiency may also be associated with a deficiency of adenosine deaminase.2,3 As with scid/scidmice, if human patients are not protected from environmental pathogens, they will die as a result of bacterial, viral, and/or mycotic infections.20
Multiple carboxylase deficiency/biotinidase deficiency
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Immunodeficiency has been reported [14] and there have been abnormalities in the function of both T and B cells. In two patients with extensive chronic mucocutaneous candidiasis, responses to Candida antigen in vitro and in vivo were absent. In one, there was a deficiency of IgA and no antibody response to immunization with pneumococcal polysaccharide; in the other, the percentage of circulating T lymphocytes was abnormally low. In this family, two previous siblings had died at eight and 39 months of age of what appeared to be the same disease [14, 38]. An unrelated patient [39] was reported to have impaired lymphocyte-suppressing activity in vitro that improved on treatment with biotin and fatty acids. In this patient, there was deficiency of prostaglandin E, as well as defective monocyte production. Deficiency of biotin in guinea pigs has been associated with decreased numbers of T and B lymphocytes [40]. All of these immunologic problems disappear with biotin treatment. One patient was initially thought to have severe combined immunodeficiency and treated with bone marrow transplantation, but manifestations persisted until treatment with biotin was initiated [41].
Autoimmune disorders associated with common variable immunodeficiency: prediction, diagnosis, and treatment
Published in Expert Review of Clinical Immunology, 2022
Niloufar Yazdanpanah, Nima Rezaei
There are reports suggestive of a lower frequency of T cells in CVID patients with autoimmune complications [64]. Nevertheless, T cell impairment is not severe because the condition is classified as severe combined immunodeficiency with CD4+ T cell count lower than 200 or significantly impaired T cell proliferation and function. Chapel et al. reported low fraction of CD8+ T cells could be representative of the risk of developing autoimmunity [9]. Bateman et al. demonstrated that autoimmunity in CVID is associated with a reduced number of CD8+ T cells and an increased number of mature differentiated CD8+ T cells [73]. Although various reports are indicative of the reduced frequency of CD4+ T cells in CVID, cases associated with autoimmunity represented a significant reduction in CD4+ T cells, in particular CD4+ Tregs [82,94]. In addition, enhanced populations of T helper (Th)1, Th17, and T follicular helper (Tfh) cells have been reported in patients with CVID-associated autoimmunity [95,96]. Furthermore, CCR7+ T cells that are immune-regulatory cells are decreased in CVID patients with autoimmune conditions [97]. Taken together, current evidence points toward an extended dysregulation in different components of the immune system, which not only affect B cells, but also influence other immune cells, including different T cell phenotypes.
JAK3 inhibitors for the treatment of inflammatory and autoimmune diseases: a patent review (2016–present)
Published in Expert Opinion on Therapeutic Patents, 2022
Chengjuan Chen, Dianxiang Lu, Tao Sun, Tiantai Zhang
JAKs have seven distinct Janus homology domain 1–7(JH1-7) regions and contain approximately 1150 amino acid residues with about 120–130 kDa molecular weights [3]. JAK3 has a cysteine residue at position 909 (Cys909) in its amino acid sequence, which is replaced by a serine residue at the same position in the other three JAK isoforms [4]. In addition to JAK3, only 10 other kinases possess a Cys909 residue in the ATP-binding site, and most covalent inhibition strategies target Cys909 to design selective inhibitor [5]. In contrast to the ubiquitous expression of the other three JAK family members, JAK3 is predominantly expressed in hematopoietic tissue cells, such as NK cells, bone marrow cells, activated B lymphocytes, and T lymphocytes. The leukocyte-specific JAK3 was uniquely associated with a shared receptor subunit of the common gamma chain (γc) for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, which regulate the growth and maturation of NK cells, B cells, and T cells [6]. The loss-of-function mutations of JAK3 caused severe combined immunodeficiency syndrome (SCID) [7], which further supported the importance of JAK3 in the immune system. Based on the structural and functional characteristics of the four JAK family subtypes, as well as specific tissue distribution, JAK3 has emerged as an ideal target for the treatment of inflammatory or autoimmune diseases [8].
The molecular immunology of human susceptibility to fungal diseases: lessons from single gene defects of immunity
Published in Expert Review of Clinical Immunology, 2019
Over the next decade, the hypothesis of an immunological defect underlying CMC was pursued. Glanzmann and Riniker, in 1950, reported two cases in whom widespread disease with C. albicans was associated with progressive lymphocytopenia and terminal pancytopenia [30]. This congenital immunodeficiency, marked by agammaglobulinemia as well as lymphopenia, was subsequently reported by others, was termed ‘Swiss-type lymphopenic agammaglobulinemia’ [31,32], and was clearly distinct from Bruton’s agammaglobulinemia by the presence of lymphopenia (eventually associated with defective development in the thymus by Nezelof [33]) and to widespread candidiasis. Some presentations implied an autosomal recessive basis, while others were thought to be transmitted in X-linked recessive manner. Ultimately, this naturally occurring immunodeficiency syndrome was recognized as not representing a single disease entity, but rather was a heterogeneous group of disorders, that came to be known as ‘severe combined immunodeficiency’. In addition to the insights these disorders provided on human lymphoid immunity and development, they also provided the first evidence of a human mycosis due to an underlying, quantifiable immunologic defect. The personal nature of why some humans were more susceptible to fungal disease than others could now be assessed mechanistically.