Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 21-year-old male patient with non-Hodgkin's lymphoma (diffuse large T-cell type, clinical stage IV) received allogeneic bone marrow transplantation (BMT) from a partially HLA-mismatched unrelated donor in July 1998 and achieved complete remission. Thereafter, he suffered from chronic graft-versus-host disease (GVHD) and was continuously administered immunosuppressive drugs for a long time. Two years after the BMT, he complained of severe pain in the right knee, which was swollen, and was diagnosed as having pneumococcal purulent genual arthritis. He underwent arthroscopic synovectomy and was administered systemic and intra-articular antibiotics, leading to a gradual improvement. Streptococcal infections are often seen in patients in the late phase after allogeneic BMT because of immunodeficiency associated with chronic GVHD and hyposplenism. Most streptococcal infections are respiratory tract infections and septicemia, and there have been very few reports on cases of purulent genual arthritis. Administration of prophylactic antibiotics and control of chronic GVHD, which is a risk factor of pneumococcal infection, seem to be important to prevent purulent genual arthritis.
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PMID:Pneumococcal purulent genual arthritis after allogeneic bone marrow transplantation. 1202 38

People with asplenia are at risk for infections due to many causative agents, mainly Streptococcus pneumoniae. Among adults, splenectomy is the most frequent etiology of hyposplenism followed with chronic hematological and connective diseases. Physiopathology of the immunologic impairment due to hyposplenia is multifactorial. Physicians and even patients must be aware of overwhelming sepsis occurring on these conditions. The prognosis of these life-threatening infections is related to the precocity of the treatment onset. These infections, mainly due to S. pneumoniae (50-90% of cases) could be prevented with appropriate precautions. Patients presenting with asplenia must be largely vaccinated against these infectious agents: S. pneumoniae, Haemophilus influenzae b, and possibly Neisseiria meningitidis. Oral phenoxymethylpenicillin seems to be the simplest chemoprophylaxis (despite the global increase of pneumococcal strains with reduced susceptibility). Duration of treatment following splenectomy is discussed: The French medicine agency (AFSSAPS) recommends a 2-year treatment after surgery and for patients having functional hyposplenism (persistency of Howell-Jolly bodies) and/or associated immunodeficiency. Despite these prevention policies, the patient must be informed of the risk of very severe infection.
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PMID:[Prevention and infection in adults patients with hyposplenism]. 1562 52

Calcium (Ca²⁺ ) acts as a ubiquitous second messenger, and normal cell and tissue physiology strictly depends on the precise regulation of Ca²⁺ entry, storage, and release. Store-operated Ca²⁺ entry (SOCE) is a major mechanism controlling extracellular Ca²⁺ entry, and mainly relies on the accurate interplay between the Ca²⁺ sensor STIM1 and the Ca²⁺ channel ORAI1. Mutations in STIM1 or ORAI1 result in abnormal Ca²⁺ homeostasis and are associated with severe human disorders. Recessive loss-of-function mutations impair SOCE and cause combined immunodeficiency, while dominant gain-of-function mutations induce excessive extracellular Ca²⁺ entry and cause tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK). TAM and STRMK are spectra of the same multisystemic disease characterized by muscle weakness, miosis, thrombocytopenia, hyposplenism, ichthyosis, dyslexia, and short stature. To date, 42 TAM/STRMK families have been described, and here we report five additional families for which we provide clinical, histological, ultrastructural, and genetic data. In this study, we list and review all new and previously reported STIM1 and ORAI1 cases, discuss the pathomechanisms of the mutations based on the known functions and the protein structure of STIM1 and ORAI1, draw a genotype/phenotype correlation, and delineate an efficient screening strategy for the molecular diagnosis of TAM/STRMK.
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PMID:Tubular aggregate myopathy and Stormorken syndrome: Mutation spectrum and genotype/phenotype correlation. 3144 44

Store-operated Ca²⁺ entry (SOCE) is a ubiquitous and essential mechanism regulating Ca²⁺ homeostasis in all tissues, and controls a wide range of cellular functions including keratinocyte differentiation, osteoblastogenesis and osteoclastogenesis, T cell proliferation, platelet activation, and muscle contraction. The main SOCE actors are STIM1 and ORAI1. Depletion of the reticular Ca²⁺ stores induces oligomerization of the luminal Ca²⁺ sensor STIM1, and the oligomers activate the plasma membrane Ca²⁺ channel ORAI1 to trigger extracellular Ca²⁺ entry. Mutations in STIM1 and ORAI1 result in abnormal SOCE and lead to multi-systemic disorders. Recessive loss-of-function mutations are associated with CRAC (Ca²⁺ release-activated Ca²⁺) channelopathy, involving immunodeficiency and autoimmunity, muscular hypotonia, ectodermal dysplasia, and mydriasis. In contrast, dominant STIM1 and ORAI1 gain-of-function mutations give rise to tubular aggregate myopathy and Stormorken syndrome (TAM/STRMK), forming a clinical spectrum encompassing muscle weakness, thrombocytopenia, ichthyosis, hyposplenism, short stature, and miosis. Functional studies on patient-derived cells revealed that CRAC channelopathy mutations impair SOCE and extracellular Ca²⁺ influx, while TAM/STRMK mutations induce excessive Ca²⁺ entry through SOCE over-activation. In accordance with the opposite pathomechanisms underlying both disorders, CRAC channelopathy and TAM/STRMK patients show mirror phenotypes at the clinical and molecular levels, and the respective animal models recapitulate the skin, bones, immune system, platelet, and muscle anomalies. Here we review and compare the clinical presentations of CRAC channelopathy and TAM/STRMK patients and the histological and molecular findings obtained on human samples and murine models to highlight the mirror phenotypes in different tissues, and to point out potentially undiagnosed anomalies in patients, which may be relevant for disease management and prospective therapeutic approaches.
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PMID:STIM1/ORAI1 Loss-of-Function and Gain-of-Function Mutations Inversely Impact on SOCE and Calcium Homeostasis and Cause Multi-Systemic Mirror Diseases. 3325 Jul 86

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