Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is a paradoxical relationship between immunodeficiency diseases and autoimmunity. While not all individuals with immunodeficiency develop autoimmunity, nor are all individuals with autoimmunity immunodeficient, defects within certain components of the immune system carry a high risk for the development of autoimmune disease. Inherited deficiencies of the complement system have a high incidence of systemic lupus erythematosus (SLE), glomerulonephritis, and vasculitis. Carrier mothers of children with chronic granulomatous disease, an X-linked defect of phagocytosis, often develop discoid lupus. Several antibody deficiencies are associated with autoimmune disease. Autoimmune cytopenias are commonly observed in individuals with selective IgA deficiency and common variable immune deficiency. Polyarticular arthritis can be seen in children with X-linked agammaglobulinemia. Combined cellular and antibody deficiencies, such as Wiskott-Aldrich syndrome, carry an increased risk for juvenile rheumatoid arthritis and autoimmune hemolytic anemia. Several hypothetical mechanisms have been proposed to explain the associations between autoimmunity and immunodeficiency. Immunologic defects may result in a failure to exclude microbial antigens, resulting in chronic immunologic activation and autoimmune symptoms. There may be shared genetic factors, such as common HLA alleles, which predispose an individual to both autoimmunity and immunodeficiency. Defects within one component of the immune system may alter the way a pathogen induces an immune response and lead to an inflammatory response directed at self-antigens. An understanding of the immunologic defects that contribute to the development of autoimmunity will provide an insight into the pathogenesis of the autoimmune process.
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PMID:The association between immunodeficiency and the development of autoimmune disease. 893 26

Bruton's XLA and DiGeorge syndrome patients show that two basic immune systems are distinct from each other in humans - thymus-dependent cell-mediated immunodeficiencies vs. antibody-based immunodeficiencies. The appendix-sacculus lymphoid organ of rabbits, like the bursa of Fabricius, represents a central lymphoid organ. Chronic granulomatous disease of childhood (CGD) revealed that phagocytosis killing of catalase-positive microorganisms employ oxidative burst. Bone marrow transplantation (BMT) proved life saving in severe combined immunodeficiency (SCID). The first BMT cured XSCID and the second BMT cured a complicating aplastic anemia launching BMT as a treatment of many diseases. Now 75 fatal diseases have been cured by myeloablative BMT. BMT also cured experimental autoimmune diseases. BMT alone did not cure lupus with polyarthritis in MRL/lpr mice or polyarthritis in NZB/KN mice, but BMT plus bone (stromal cell) transplants cured these diseases. Autoimmune diseases and lethal glomerulonephritis were prevented or cured in BXSB mice by mixed allogeneic plus syngeneic BMT. X-linked Hyper IgM syndrome (XHIM) was also cured by BMT from a 2-year-old MHC-matched sibling donor. Nonmyeloablative BMT plus mesenchymal stem cells (stromal cells) was effective treatment for a form of collagen-vascular disease and also a lethal form of hypophosphatasia. Mannan-binding lectin, an opsonin that activates the complement system when mutated and at low levels in blood, opens a door to frequent infections throughout childhood and adult life. This new immunodeficiency is based on genetic mutations that involve a native defense system.
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PMID:Cellular immunology in a historical perspective. 1219 Sep 28

Since the original identification of Bruton's tyrosine kinase (BTK) as the gene defective in the primary immunodeficiency X-linked agammaglobulinemia (XLA) in 1993, our knowledge on the physiological function of BTK has expanded impressively. In this review, we focus on the role of BTK during B cell differentiation in vivo, both in the regulation of expansion and in the developmental progression of pre-B cells in the bone marrow and as a crucial signal transducer of signals downstream of the IgM or IgG B cell antigen receptor (BCR) in mature B cells governing proliferation, survival, and differentiation. In particular, we highlight BTK function in B cells in the context of host defense and autoimmunity. Small-molecule inhibitors of BTK have very recently shown impressive anti-tumor activity in clinical studies in patients with various B cell malignancies. Since promising effects of BTK inhibition were also seen in experimental animal models for lupus and rheumatoid arthritis, BTK may be a good target for controlling autoreactive B cells in patients with systemic autoimmune disease.
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PMID:BTK Signaling in B Cell Differentiation and Autoimmunity. 2634 Nov 10

The development of T-cell lymphomas, granulomatous reactions, and autoimmunity has been observed in immunodeficiency due to milder forms of recombination activating gene (RAG) deficiency. A few cases of cutaneous clonal papulonodular CD8 lymphocytic infiltrates and cutaneous CD8 granulomatous T-cell lymphoma have been described in association with common variable immunodeficiency, and with X-linked agammaglobulinemia. We describe a 15-year-old girl with several autoimmune disorders and recurrent infections that presented with several nodules on her cheek. Histopathological studies demonstrate histological, immunohistochemical, and molecular findings compatible with a primary cutaneous clonal CD8 T-cell lymphoproliferative disorder. Vacuolar interface changes were also seen in the involved skin, reminiscent of cutaneous lupus erythematosus. Molecular genetic analysis revealed a germline novel homozygous missense mutation in RAG1 (T1003>C). The parents were heterozygous carriers. The facial cutaneous lesions recurred despite local radiation therapy. Because of recurrent life-threatening systemic infections, allogeneic bone marrow transplantation was performed. The pathogenesis of this primary cutaneous clonal CD8 T-cell lymphoproliferative disorder may have been related to a chronic stimulation of autoreactive T cells in the involved skin paired with reduced RAG1 activity.
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PMID:Primary Cutaneous Clonal CD8+ T-Cell Lymphoproliferative Disorder Associated With Immunodeficiency due to RAG1 Mutation. 3131 95