Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Schizophrenia and certain forms of idiopathic mental retardation may result from covert immune complex disease of the basal lamina of the choroid plexus, a process already known to cause covert transport dysfunction in similar structures of, for example, skin, bowel, kidney, and endocrines. Plexial attack could lead to cerebrospinal fluid contamination and then, via an "open" ependyma, to neurotransmitter dysfunction in the periventricular limbic brain. The immune complex mechanism implies polygenic induction, direct or autoimmune, of immune sensitivity to exogenous agents and is thus compatible with the genetic picture in schizophrenia. Candidate agents include viral coat peptides and cereal grain glutens. The glutens are known to cause immune complex skin and bowell disease variants, and some empirical evidence links them to schizophrenia. Only newer immunofluorescence methods can detect the pathology, which is otherwise silent. Systemic lupus erythematosus provides a model since it is a genetic immune complex disease strongly associated with schizophreniform psychoses, exhibits choroid plexial immunofluorescence but no central nervous system pathology by ordinary methods, and may be triggered by viruses.
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PMID:Covert transport dysfunction in the choroid plexus as a possible cause of schizophrenia. 4 42

Purine nucleoside phosphorylase (PNP) deficiency is a rare inherited disease accounting for approximately 4% of patients with severe combined immunodeficiency. Thirty-three patients have been reported. PNP-deficient patients suffer from recurrent infections, usually beginning in the first year of life. Two thirds of patients have evidence of neurologic disorders. Findings range from spasticity to developmental delay, to mental retardation. One third of patients develop autoimmune disease. The most common manifestation of this is autoimmune hemolytic anemia. Idiopathic thrombocytopenic purpura and systemic lupus erythematosis have also been reported. Patients usually present with infections but approximately one fourth have come to medical care initially for neurological problems. In PNP deficiency, T- and B-cell immunity are affected. T-cell function may be profoundly deficient, may be normal at birth and then decrease with time, or may fluctuate repeatedly between low and normal. B-cell function can be normal but is deficient in approximately one third of patients. PNP protein is a trimer of approximately 90,000 daltons. It is found in most tissues of the body but is at highest levels in lymphoid tissues. This tissue distribution explains why the lymphoid system is predominantly affected in PNP deficiency. Many mechanisms have been proposed to explain the metabolic toxicity in PNP deficiency. The elevated dGTP found in PNP deficiency is thought to inhibit ribonucleotide reductase and, thus, impede cell division. Depressed GTP levels may correlate with neurologic dysfunction. The gene for PNP has been cloned; it is located on the long arm of chromosome 14. Studies of a mutant PNP gene isolated from one patient showed that a point mutation resulting in an amino acid substitution was responsible for PNP deficiency. PNP deficiency has a grave prognosis. No patient has reached the third decade of life. Twenty-nine of the 33 reported patients have died from their disease. Prenatal diagnosis is currently available. Many different therapies have been utilized for PNP deficiency including bone marrow transplantation, red cell transfusions, and supplementation of the diet with purines and pyrimidines. None of these therapies has been consistently successful. In light of the poor prognosis for PNP deficiency, bone marrow transplantation should be considered for all patients. In the future, improved forms of therapy such as gene therapy may become available.
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PMID:Purine nucleoside phosphorylase deficiency. 193 Oct 7

To study the incidence of circulating anti-CNS antibodies in childhood neurologic diseases, a population study was undertaken. Serum samples were obtained from a total of 348 children and stored at -80 degrees C until being studied. The samples were collected when routine blood tests were being performed. In all cases informed consent was obtained. This study was approved by hospital ethics review committees. One hundred and ninety-nine of the samples were from children with no known neurologic illnesses and served as the control group. One hundred and twenty-one of the samples were from children with epilepsy and the remaining 28 from a number of different neurologic conditions. The serum samples were screened against normal, adult, autopsy-derived cerebellar and frontal cortex tissue sections and Western blots. Serum immunoreactivity was revealed using HRP-conjugated anti-human IgG. Significant findings included: (1) patients with epilepsy had an increased incidence of anti-CNS reactivity as revealed on frontal cortex immunoblots (p less than 0.05) but not on cerebellar immunoblots; (2) there was an increase in the incidence of immunoblot reactivity with age in the controls and the neurology cases; (3) there was an increased incidence of immunoblot reactivity in those cases with a presumed inflammatory central or peripheral neurologic disease; (4) in six additional cases with opsoclonus-myoclonus there was cerebellar-specific immunoreactivity with identified antigenic molecular weights of 27 and 35, and 62 kDaltons; (5) in 31 additional cases of systemic lupus erythematosus there was significant immunoblot reactivity (p less than 0.001) when compared to a subset of age-matched controls. There was no difference in immunoreactivity between males and females. There was no significant increase in immunoreactivity in those children with cognitive disturbances including developmental delay and mental retardation.
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PMID:Anti-CNS antibodies in childhood neurologic diseases. 273 81

Gualtieri and Hicks (1985) proposed that male vulnerability for neurodevelopmental disorders (NDs) was partially due to intrauterine immune attack of the fetus. One group of mothers with heightened immunoreactivity might be women with immune disorder. This was tested within an epidemiological sample of 17,283 mother/child pairs. Maternal immune disorders considered were ulcerative colitis or asthma. NDs in the child included: cerebral palsy, mental retardation, seizures, articulation disorder, reading, or arithmetic disability, verbal or performance aptitude deficits, and attention deficit disorder. Unlike prior studies, we controlled for demographic perinatal variables that might confound interpretation of the data. Results indicated that immune dysfunction in the mother, be it autoimmune (ulcerative colitis) or defensive (asthma) was not associated with an increased incidence of any NDs in the offspring, but mothers with ulcerative colitis did have a disproportionate number of offspring who were non-right handed. Few variables discriminated between the children of ulcerative colitis mothers who became right handed when compared to those who did not. We suggest that a) only certain maternal autoimmune disorders such as systemic lupus erythematosus (but not ulcerative colitis or asthma) elevate the risk of intrauterine immune attack and b) the elevated rate of non-right handed offspring among ulcerative colitis mothers was not an instance of immune attack but instead represents some kind of genetic association.
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PMID:A test of the immunoreactive theory for the origin of neurodevelopmental disorders in the offspring of women with immune disorder. 753 15

The case of a 40-year-old woman with Werner's syndrome associated with systemic lupus erythematosus (SLE) is reported. The patient exhibited short stature, slender extremities, thinned hair, high-pitched voice, cataracts, ulceration of the fingers, and mental retardation. Malar erythema, photosensitivity, and proteinuria had been noted since age 34. The serum contained high titers of antibodies to dsDNA, Sm, nRNP, and SS-A/Ro. The simultaneous presence of Werner's syndrome and SLE could be a coincidental occurrence of the two diseases, although it might be due to an abnormality in replication or degeneration of DNA leading to the development of both diseases.
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PMID:A case of Werner's syndrome associated with systemic lupus erythematosus. 778 63

A case of ulcerative lupus vulgaris, confirmed by polymerase chain reaction (PCR) is reported. The initial lesion of our case was a papule on the nose, which progressed during antituberculous treatment and caused cartilage destruction and ectropion. Immunological analysis revealed CD4 lymphocytopenia, and the possibility of idiopathic CD4 lymphocyte deficiency was considered. In addition, the patient had primary amenorrhoea, mental retardation and inversion of chromosome 14. CD4 lymphocytopenia and chromosomal abnormality are the possible causes of antituberculous treatment failure.
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PMID:Refractory ulcerative lupus vulgaris associated with CD4 lymphocytopenia, inversion of chromosome 14, primary amenorrhoea and mental retardation. 922 26

Human cytomegalovirus (CMV) infection can be life threatening in the immune compromised and is associated with congenital defects and / or mental retardation in the neonate. The demonstrated association between CMV infection and rheumatoid factor (RF) raised the possibility of an induction of an autoimmune response upon vaccination with a candidate CMV vaccine, glycoprotein gB (UL55). The antibody responses generated after injections of an adenovirus-gB construct (Ad-gB) were studied in autoimmune-prone (MRL/mpj) and normal (BALB.k, C3H, and BALB/c) mice. Enzyme-linked immunosorbent assay and immunoblot analyses were done to identify the autoantibodies produced following immunization. Immunization with Ad-gB induced a significant IgG anti-viral response in all strains tested (p < 0.0001) compared to phosphate-buffered saline or HeLa controls. Ad-gB induced a significant IgG autoantibody response (p > 0.005) to the U1-70 kDa spliceosome protein in both autoimmune and normal strains whereas immunization with recombinant human La/SS-B did not. Autoantibodies to U1-70 kDa are part of the anti-ribonucleoprotein response seen in systemic lupus erythematosus and mixed connective tissue disease. Low levels of IgG RF and anti-double-stranded DNA antibodies were also induced. This study raises concern that immunization with CMV gB in individuals genetically predisposed to autoimmunity could trigger the development or acceleration of an autoimmune disease.
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PMID:Recombinant cytomegalovirus glycoprotein gB (UL55) induces an autoantibody response to the U1-70 kDa small nuclear ribonucleoprotein. 1055 20

This reports describes a 12-year-old Japanese female with Noonan syndrome who had antiphospholipid syndrome and moyamoya-like vascular changes. She presented choreic movements in her face and extremities. She manifested phenotypic features of Noonan syndrome with short stature, mental retardation, and a webbed neck. Magnetic resonance angiography revealed occlusion of bilateral internal carotid arteries and moyamoya-like vascular changes around the basal ganglion region. Pimozide completely resolved the patient's choreic movements. Tests for anticardiolipin antibody and lupus anticoagulant were positive. The patient has manifested no symptoms for 2 years with pimozide, aspirin, and growth hormone treatment, without further aggravation of moyamoya-like vascular changes. This article is the first report of Noonan syndrome with antiphospholipid syndrome and moyamoya-like vascular lesions.
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PMID:Noonan syndrome, moyamoya-like vascular changes, and antiphospholipid syndrome. 1551 21

Congenital insensitivity to pain with anhidrosis (CIPA) is an autosomal recessive disorder caused by mutations in the neurotrophic tyrosine receptor kinase 1 (NTRK1) gene which encodes the receptor for nerve growth factor (NGF). We report the clinical course in three sibs with CIPA and proven NTRK1 gene mutations with a follow-up over a 25-year period in one of them. They had the characteristic clinical features of an abnormally high pain threshold, and mental retardation; in addition their clinical course was marked by the occurrence of early onset renal disease with recurrent microhematuria and proteinuria and frequent observations of increased serum creatinine and blood urea levels. Light microscopy study of a renal biopsy performed in one of them at age of 20 months showed focal glomerulosclerosis, interstitial fibrosis and tubular atrophy. This patient and his younger brother died because of renal failure at the age of 25 years and 14 years, respectively. The sister still alive showed renal impairment and deep venous thrombosis associated with lupus anticoagulant activity, decrease of circulating autoreactive CD5 (+) B lymphocytes and increased urinary levels of IgG and kappa and lambda light chains, suggesting a possible defect in regulation of B-lymphocyte function. In the light of the NGF-related molecular defect, the extraneurological tissue involvement in CIPA might in part reflect dysregulation of immune mechanisms which possibly brings about a chronic inflammatory response. This, in turn, could result in renal disease which should be mentioned among the life-threatening complications associated with this disorder.
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PMID:Congenital insensitivity to pain with Anhidrosis (NTRK1 mutation) and early onset renal disease: clinical report on three sibs with a 25-year follow-up in one of them. 1613 53

Enchondromas are a feature of several constitutional disorders of bone, and the classification of different nosologic entities is still provisional. Among these disorders, spondyloenchondrodysplasia (SPENCD), as outlined by Schorr et al. [1976], is defined by the presence of radiolucent spondylar and metaphyseal lesions that represent persistence of islands of chondroid tissue within bone. Careful review of radiographic findings is needed to distinguish SPENCD from the many other disorders combining enchondromas with spinal lesions. Even when strict criteria are applied, it appears that SPENCD is clinically heterogeneous, as some SPENCD patients are neurologically intact while others present with spasticity, mental retardation, and cerebral calcifications in different combinations, and it has been suggested that SPENCD should be divided in two types. We herein report ten individuals from six families with SPENCD and illustrate the radiographic changes. Seven individuals had CNS manifestations including spasticity, developmental delay, and late-onset cerebral calcifications. We also noted that six individuals had clinical manifestations of autoimmunity (auto-immune thrombocytopenic purpura, auto-immune hemolytic anemia, auto-immune thyroiditis, and SLE) and one had been diagnosed with immune deficiency. Neurological and autoimmune manifestations were seen in different combinations within one single family. These observations suggest that SPENCD may be a single entity defined by specific radiographic features, but with remarkably pleiotropic manifestations that include CNS disease (spasticity, mental retardation, and calcifications), as well as immune dysregulation ranging from autoimmunity to immunodeficiency. The notion of recessive inheritance hitherto assumed is challenged by the observation of two apparently dominant pedigrees.
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PMID:Spondyloenchondrodysplasia with spasticity, cerebral calcifications, and immune dysregulation: clinical and radiographic delineation of a pleiotropic disorder. 1647 Jun


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