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)

In an attempt to map the gene (or genes) controlling the synthesis fo the fourth component of complement (C4), we performed linkage studies in a family with hereditary C4 deficiency. The proband, a seven-year-old boy with lupus erythematosus, consistently lacked deteftable serum C4 by both functional and protein measurements. The complement defect was transmitted as an autosomal recessive disorder. Eight of 15 family members were considered to be heterozygotes, seven because of low C4 levels and one because of genetic data (obligate heterozygote). The gene (or genes) coding for C4 deficiency appeared to be linked to the major histocompatibility complex (A2,B12,DW2 on the maternal side and A2,BW15,LD108 on the paternal side) and to other markers known to be in close proximity to the histocompatibility complex on chromosome 6 (phosphoglucomutase-3, glyoxalase-1 and properdin factor B).
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PMID:Linkage between the gene (or genes) controlling synthesis of the fourth component of complement and the major histocompatibility complex. 13 91

Transcobalamin II (TC II) is a serum protein responsible for transporting vitamin B12 to the cells. A previous observation of a child with congenital TC II deficiency and agammaglobulinemia suggested that this protein plays an important role in the immune response. Accordingly, TC II levels ere determined in 32 patients with autoimmune disease (AID) (i.e. 26 with lupus erythematosus, 4 with dermatomyositis, and 2 with autoimmune hemolytic anemia) and in 40 patients with acquired immunodeficiency due to chemotherapy. It was found that elevated TC II levels corresponded to active phases of AID. Changes in TC II levels correlated better with the clinical course of AID than complement, antinuclear antibody or native DNA binding capacity. This suggests that TC II could be a valuable parameter in following up activity of AID.
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PMID:[Increase of unsaturated transcobalamine II in autoimmune diseases; effect of immunosuppressive therapy (proceedings)]. 69 99

Significant associations have been found between the HLA antigens or haplotypes and certain diseases and deficiencies. These associations have opened up new areas of clinical investigation. In man, associations have been shown between the presence of Hodgkin's Disease and a number of cross-reacting HLA types (BW5, BW15, BW18), between systemic Lupus erythematosus and HLA type BW15 in Caucasians and BW35 in blacks, between HLA B37 and ankylosing spondylitis in Caucasians, between HLA B8 and gluten-sensitive enteropathy and between HLA B13 and psoriasis, a disease having a strong hereditary element. In ophthalmology, Shin and Becker have shown that the prevalence of HLA B7 and B12 antigens was significantly higher in patients with primary open-angle glaucoma than in the non-glaucomatous population. The purpose of this communication is to report the presence of HLA B27 antigen in the mother and two siblings with keratoconus.
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PMID:HLA antigens and keratoconus. 91 Nov 19

As a result of a careful study of 150 patients with systemic lupus erythematosus (SLE) they could be distributed in 8 clinico-immunologic groups of the disease. Group I included patients with lupus nephritis manifesting by the nephrotic syndrome, group II patients with systemic vasculitis, group III patients with CNS injuries, group IV was made up of patients with discoid lupus, group V of patients with the prevailing damage to the respiratory organs, group VI of patients with hematologic disorders, group VII of patients with generalized visceral SLE, and group VIII included patients with generalized "peripheral" SLE. It was established on HLA typing that on the whole the patients with SLE manifested the increased frequency of HLAA11, B7, B35, DR2 and DR3 antigens. The patients' groups differed in primary carriership of certain antigens. Group I demonstrated a significant increase of the frequency of HLAA9, B13 and DR3, group II of HLADR2, group III of HLAB7, B12 and DR2, group IV of HLAB12, B13 and DR3, group V of HLAA1 and B8, group VII of HLADR1, and group VIII of HLAB35 and DR3. Group VI which was not numerous did not show any clinicogenetic association. The clinicoimmunologic polymorphism can be partially due to the genetic heterogeneity of certain patients' groups with SLE.
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PMID:[Subgroups of patients with systemic lupus erythematosus]. 278 84

The alanine/valine (A/V) gene polymorphism of 5, 10-methylenetetrahydrofolate reductase (MTHFR), one of the key enzymes catalyzing remethylation of homocysteine, has been reported and the VV genotype is associated with increased plasma homocysteine levels as a result of the reduced activity and increased thermolability of this enzyme. Although previous studies have suggested that the VV genotype is a risk factor for arterial occlusive disease, whether the VV genotype is a risk factor for venous thrombosis is still controversial. Here we screened 72 Japanese patients with deep venous thrombosis (DVT) and 85 controls for this mutation, and we measured plasma levels of homocysteine to determine whether the thermolabile variant with the VV genotype is a risk factor for DVT in a Japanese population. Of the 72 patients with DVT, 10 (13.9%) were found to be homozygous for the VV genotype, and in 6 (7.0%) of 85, control individuals and the difference was not significant (odds ratio=2.12, 95% CI=0.73-6.16, p=0.19). When we divided the DVT patients into subgroups, with and without predisposition of thrombophilia, including deficiencies of proteins C and S, plasminogen, and lupus anticoagulant, the prevalence of the VV genotype in DVT patients with predisposition was significantly higher than that of the normal controls (odds ratio=5.99, 95% CI=1. 56-22.96, p=0.01). However, the prevalence of the VV genotype in DVT patients without predisposition was not significantly different from that of the normal controls (odds ratio=1.20, 95% CI=0.32-4.47, p=0. 75). The plasma homocysteine levels in patients with DVT (11.6+/-5.2 nmol/ml) was not significantly different from that of the control subjects (11.6+/-3.7 nmol/ml). Individuals with the VV genotype showed higher plasma homocysteine levels (15.4+/-6.9 nmol/ml) than did individuals with the AV genotype (11.2+/-3.7 nmol/ml, p=0.009) or in individuals with the AA genotype (11.1+/-4.2 nmol/ml, p=0.004). Serum folate and vitamin B12 levels were not correlated with the plasma homocysteine levels. In conclusion, even though homozygosity for the VV genotype of the MTHFR gene was associated with higher plasma homocysteine levels, we found no association between plasma levels of homocysteine and DVT or between the genotype of the MTHFR gene and the DVT incidence. However, we found that the VV genotype of the MTHFR gene is a risk factor for DVT only when combined with the predisposition of thrombophilia.
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PMID:Common C677T polymorphism in the methylenetetrahydrofolate reductase gene increases the risk for deep vein thrombosis in patients with predisposition of thrombophilia. 1070 28

A 54-year-old man of Persian origin presented to our department with a 1-year history of ulcers on the right leg that had been unresponsive to numerous topical treatments, accompanied by lymphedema of the right leg. Medical history included hypergonadotropic hypogonadism, which had not been further investigated. He was treated for 20 years with testosterone IM once monthly, which he stopped a year before the current hospitalization for unclear reasons. The patient reported no congenital lymphedema. Physical examination revealed two deep skin ulcers (Figure 1) on the right leg measuring 10 cm in diameter with raised irregular inflammatory borders and a boggy, necrotic base discharging a purulent hemorrhagic exudate. Bilateral leg pitting edema and right lymphangitis with lymphadenitis were noted. He had low head hair implantment, sparse hair on the body and head, hyperpigmentation on both legs, onychodystrophia of the toenails (mainly the large toe and less prominent on the other toes), which was atrophic lichen-planus-like in appearance and needed no trimming (Figure 2), normal hand nails, oral thrush, and angular cheilitis. Other physical findings were gynecomastia, pectus excavatum, small and firm testicles, long extremities, asymmetrical goiter, systolic murmur 2/6 in left sternal border, and slow and inappropriate behavior. The patient's temperature on admission was 39 degrees C. Blood cultures were negative for bacterial growth. Results of laboratory investigations included hemoglobin (11.2 g/dL), hematocrit (26.8%), normal mean corpuscular volume and mean corpuscular hemoglobin volume, and red blood cell distribution width (16%). Blood smear showed spherocytes, slight hypochromia, anisocytosis, macrocytosis, and microcytosis. Blood chemistry values were taken for iron (4 micro g/dL [normal range 40-150 micro g/dL]), transferrin (193 mg/dL [normal range 220-400 mg/dL]), ferritin (1128 ng/mL [normal range 14-160 ng/mL]), transferrin saturation (1.5% [normal range 20%-55%]), serum folate (within normal limits), and vitamin B12 (within normal limits). Direct Coombs' test equaled positive 2 + IgG. All these values indicated anemia of chronic diseases combined with hemolytic anemia. Further blood work-up tested antinuclear antibody (positive <1:80 homogeneous pattern), rheumatoid factors (143 IU/mL [positive >8.5 IU/mL]), C-reactive protein (286 mg/L [normal range 0-5 mg/L]), anticardiolipin IgM antibody (9.0 monophosphoryl lipid U/mL [normal range 0-7.00 MPL U/mL]) and antithrombin III activity (135% [normal range 74%-114%]). Results of other blood tests were within normal limits or negative, including lupus anticoagulant, beta2 glycoprotein, anticardiolipin IgG Ab, anti-ss DNA Ab, C3, C4, anti-RO, anti-LA, anti-SC-70, anti-SM Ab, P-ANCA, C-ANCA, TSH, FT4, anti-T microsomal, antithyroglobulin, protein C activity, protein S free, cryoglobulins, serum immunoelectrophoresis, VDRL, hepatitis C antibodies, hepatitis B antigen, and human immunodeficiency virus. Endocrinological work-up examined luteinizing hormone (22.9 mIU/mL [normal range for adult men 0.8-6 mIU/mL]), follicle stimulating hormone (49.7 mIU/mL [normal range for adult men 1-11 mIU/mL]), testosterone (0.24 ng/mL [normal range for adult men 2.5-8.0 ng/mL]), bioavailable testosterone (0.02 ng/mL [normal range for adult men >0.6 ng/mL]), and percent bioavailable test (8.1% [normal value >20%]). These results indicate hypergonadotropic hypogonadism. Plasminogen activator inhibitor 1 was 6 U (normal value 5-20 U/mL). Karyotyping performed by G-banding technique revealed a 47 XXY karyotype, which is diagnostic of Klinefelter's syndrome. Doppler ultrasound of the leg ulcers disclosed partial thrombus in the distal right femoral vein. X-rays and bone scan displayed osteomyelitis along the right tibia. Histological examination of a 4-mm punch biopsy from the ulcer border revealed hyperkeratosis, acanthosis, hypergranulosis, and mixed inflammatory infiltrate containing eosinophils compatible with chronic ulcer. Multiple vessels were seen, compatible with a healing process. Direct immunofluorescence of the biopsy revealed granular IgM in the dermo-epidermal junction. Indirect immunofluorescence was negative. Thyroid function tests showed normal thyroid stimulating hormone and free throxine4. Multinodular goiter was seen on thyroid scan and ultrasound. Thyroid fine needle aspiration was compatible with multinodular goiter (normal follicular cells, free colloid, macrophages with pigment). IV treatment with amoxicillin-clavulanic acid 1 g t.i.d. was administered for 2 weeks, with a decrease in temperature and normalization of the leukocyte level. Oral antibiotic treatment with amoxicillin-clavulanic acid was continued for 10 more days, followed by 25 days of ciprofloxacin for the osteomyelitis. Local treatment included saline soakings followed by application of Promogran (Johnson & Johnson, New Brunswick, NJ) and Kaltostat (ConvaTec Ltd., a Bristol-Myers Squibb Company, New York, NY) with slight improvement. At the same time, the patient was treated with warfarin sodium due to deep vein thrombosis under international normalized ratio 2-3. The patient was treated with IM testosterone once monthly for 1 year, which resulted in a reduction in the diameter and depth of the leg ulcers (Figure 3). Blood tests were not performed for follow-up of the immune state.
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PMID:Klinefelter's syndrome presenting with leg ulcers. 1536 65

Cardiovascular disease is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Antiphospholipid syndrome (APS) is one of the most important causes of thrombosis in SLE. In addition, an association between hyperhomocysteinemia and increased cardiovascular risk has also been reported. Our aim is to analyse the association of thrombosis with plasma total homocysteine (ptHcy), antiphospholipid antibodies (aPL) and other vascular risk factors in SLE patients. Fasting plasma levels of ptHcy, vitamin B12, folate, total cholesterol and creatinine were measured in 117 SLE patients. Clinical and immunological data were obtained from our prospective computerized database. aPL-positivity was defined according to Sapporo criteria. There was no association between aPL and ptHcy. ptHcy was higher in patients with arterial (median 13.02 versus 10.16 micromol/L, P = 0.010) but not venous thrombosis. In the subgroup analysis, this association was only seen in aPL-negative patients. In logistic regression, aPL (OR 6.60, 95% CI 1.86-23.34) and ptHcy (OR 1.10, 95% CI 1.01-1.19) were independently associated with arterial thrombosis. However, when hypertension, smoking and plasma total cholesterol were added to the model, only aPL (OR 7.38, 95% CI 2.02-26.91) and hypertension (OR 7.70, 95% CI 2.33-25.39), but not ptHcy, remained independently related to arterial events. aPL was the only variable independently related to venous thrombosis (OR 7.68, 95% CI 1.60-36.86). ptHcy concentrations are higher in SLE patients with arterial thrombosis. No interaction between homocysteine and aPL was found. Raised ptHcy may be a marker of increased vascular risk in aPL-negative SLE patients. The role of homocysteine as a marker of vascular risk may depend on the presence of traditional risk factors, although a modest intrinsic effect cannot be entirely excluded.
Lupus 2004
PMID:Homocysteine, antiphospholipid antibodies and risk of thrombosis in patients with systemic lupus erythematosus. 1564 48

The incidental discovery of neutropenia during routine blood counting represents a common problem for clinicians. However, there are no reported data of systematic evaluations of adults with incidental neutropenia. As such, this was the aim of the present study. Ninety-seven adults with incidental neutropenia were submitted to a clinical and laboratory approach including medical evaluation, complete blood count (CBC), serial CBC, direct and indirect antiglobulin test, bone marrow smear and biopsy, assessment of folate, vitamin B12 and iron status, serum liver enzymes, serum proteins, serological exams for hepatitis B and C virus, cytomegalovirus, mononucleosis, human immunodeficiency virus and toxoplasmosis, detection of lupus erythematosus cells, antinuclear and anti-DNA antibodies and rheumatoid factor, dosage of free thyroxin and thyrotropin, chest roentgenogram and abdominal echography. Chronic idiopathic neutropenia of adults was identified in 34.0% of the individuals, neutropenia due to exposure to chemical agents was seen in 16.5%, infectious diseases in 9.3%, autoimmune diseases in 9.3%, haematological diseases in 9.3%, thyroid disorders in 8.2%, ethnic neutropenia in 7.2%, drug-related neutropenia in 2.1%, cyclic neutropenia in 2.1% and iron deficiency in 2.1%. Recovery or improvement of the neutrophil count was seen upon treatment or recuperation from infectious, autoimmune, haematological and thyroid diseases and iron supplementation. We conclude that the evaluation of individuals with incidental neutropenia using a structured approach may make the identification of clinically silent diseases possible, and provide an opportunity for early treatment, avoiding complications of the diseases and consequences of neutropenia.
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PMID:Causes of incidental neutropenia in adulthood. 1680 47

Association of pernicious anemia and systemic lupus erythematosus is rare, although both diseases are autoimmune origin. We describe the case of a 40-year old man with systemic lupus erythematosus (SLE) who developed pernicious anemia. The cobalamin deficiency was revealed by macrocytic pancytopenia. After 1 month of vitamin B12 treatment, hemoglobin and white blood cell count remain normal but thrombocytopenia persists and was considered as immunologic from SLE origin requiring corticosteroids.
Lupus 2007
PMID:Pernicious anemia in a young man with systemic lupus erythematosus. 1789 7

Brief virologic news included the discovery of the virophage, a unique parasite of the giant mimivirus and the association of HHV-8 infection with a peculiar form of African diabetes. Secondly, this news focused on risk factors for arterial or venous thrombosis and therapy for auto-immune disorders. Only oral estrogen therapy increases the risk of venous thromboembolism in postmenopausal women. Despite significant homocysteine lowering, vitamin supplementation with folic acid, vitamins B6 and B12 did not reduce total cardiovascular events among high-risk patients. Patients with venous thromboembolism have a substantially increased long-term risk of subsequent cardiovascular events while obesity, systemic arterial hypertension, and diabetes are common risk factors for arterial and venous thrombosis. The non fasting ApoB/ApoA1 ratio was superior to any of the cholesterol ratios for estimation of the risk of acute myocardial infection in all ethnic groups. Preventive anticoagulation of in-patients with risk of venous thromboembolism was inadequately prescribed in many hospitals of the world. Subcutaneous administration of methotrexate was more effective than the oral administration at the same dosage in patients suffering from active rheumatoid arthritis. Hydroxychloroquine directly reduces the binding of antiphospholipid antibody-beta2-glycoprotein I complexes to phospholipid bilayers. Anti-IL-5 and anti-IL-6 antibodies were effective for the treatment of respectively hypereosinophilic syndrome and rheumatoid arthritis. The efficacy of proteasome inhibitors and mesenchymal stems cells have been demonstrated in respectively two mouse strains with lupus-like disease and steroid-resistant severe acute graft-versus-host disease. These treatments may be useful for auto-immune disorders if their long term toxicity is acceptable. In conclusion, subcutaneous injections of physiological saline, used as placebo in two different trials, enhanced in vitro activation of immunocompetent cells in healthy individuals.
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PMID:[What's new in internal medicine?]. 1926 9


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