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)

Antimitochondrial M5 type antibodies (AMA M5) have been described in patients with antiphospholipid syndrome (APS), thrombocytopenia and autoimmune hemolytic anemia. The aim of this study was to describe the clinical and immunological characteristics of a series of patients with AMA M5. We analyzed 71 patients with AMA M5 seen consecutively at our centres during the last 8 years. The clinical and immunological characteristics of diseases expression were compared with 70 consecutive disease control patients without AMA M5. Compared with the control group, AMA M5 positive patients presented higher prevalence of false positive VDRL test (P < 0.001) and thrombocytopenia (P = 0.002) with lower levels of anti-beta2 glycoprotein I antibodies. In AMA M5 patients (56 female, 15 male) a heterogeneous group of disorders were found. Twenty-seven (38%) patients fulfilled the Sapporo criteria for the classification of the APS. Laboratory criteria were met in 55 (77.5%), and clinical criteria in 31 (43.7%) patients. Six patients initially presented with non-criteria features of APS during follow-up period developed APS. Younger patients with AMA M5 should be carefully observed for the development of APS, even in the absence of serological criteria, while elderly must be screened for monoclonal gammopathy and hematological disorders.
Lupus 2007
PMID:Clinical and serological follow-up of 71 patients with anti-mitochondrial type 5 antibodies. 1789 1

The aim of this study was to describe the presenting clinical manifestations and syndromes of Filipino patients on diagnosis of systemic lupus erythematosus (SLE). We performed a retrospective review of medical records of Filipino SLE patients included in the lupus database of the University of Santo Tomas (UST) in Manila, Philippines. All patients fulfilled the American College of Rheumatology criteria for SLE. The following data were recorded: (1) demographic profile, (2) clinical manifestations on SLE diagnosis, and (3) clinical syndromes prior to and during fulfillment of diagnostic criteria for SLE and disease interval from diagnosis of a clinical syndrome to SLE diagnosis. Clinical data of 1,070 patients entered into the UST lupus database as of October 2005 were analyzed. The average age at SLE diagnosis was 28.5 +/- 11.5 (range 5-71) years, with 1,025 female and 45 male subjects. The most common presenting manifestation was arthritis (68%), followed by malar rash (49%), renal involvement (47%), photosensitivity (33%), and oral ulcers (33%). The following clinical syndromes were recorded prior to or during SLE diagnosis: nephrotic syndrome (30%), undifferentiated connective tissue disease (UCTD) (22%), autoimmune hemolytic anemia (AIHA) (6%), and idiopathic thrombocytopenic purpura (ITP) (6%). Among these, AIHA preceded the diagnosis of SLE at the longest interval (20.3 +/- 30.6, range 1-194 months). In this large database of Filipino patients with SLE, the most common presenting manifestation was arthritis, with renal involvement occurring in almost 50%. Among the clinical syndromes, nephrotic syndrome was the most common, whereas AIHA recorded the longest interval preceding SLE diagnosis, at an average of 20.3 months. Our findings are similar to data from other countries and emphasize the broad range of manifestations of SLE. The findings also reinforce the need to establish and maintain SLE databases to enhance awareness, early diagnosis, and more efficient management of the disease.
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PMID:Clinical manifestations and clinical syndromes of Filipino patients with systemic lupus erythematosus. 1831 32

Conventional treatment of autoimmune hemolytic anemia (AIHA) comprises corticosteroids and splenectomy and/or other immunosuppressive drugs for refractory/relapsed patients. Monoclonal antibodies (MoAbs) rituximab and alemtuzumab have gained widespread acceptance in the management of B-cell malignancies. More recently, they have been used to treat a number of autoantibody-mediated diseases, such as both idiopathic and secondary AIHA, with encouraging results. Herein we report an overview of the medical literature on the use of MoAbs to treat AIHA. The therapeutic mechanism of action of rituximab in the treatment of autoimmune diseases such as rheumatoid arthritis and lupus is currently a subject of considerable investigation. We have proposed that cell-associated IgG immune complexes, generated by the binding of rituximab to CD20 on B cells, may serve as decoys that attract FcgammaR-expressing effector cells and downregulate effector cell pathogenic action, thus reducing inflammation and tissue destruction in these diseases. We briefly review evidence that suggests that this immune complex decoy hypothesis plays a role in the therapeutic action of rituximab in AIHA, and we propose new measurements that should allow for a more complete evaluation of the importance of this mechanism in AIHA.
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PMID:Monoclonal antibodies: new therapeutic agents for autoimmune hemolytic anemia? 1839 24

Autoantibody-mediated diseases like myasthenia gravis, autoimmune hemolytic anemia and systemic lupus erythematosus represent a therapeutic challenge. In particular, long-lived plasma cells producing autoantibodies resist current therapeutic and experimental approaches. Recently, we showed that the sensitivity of myeloma cells toward proteasome inhibitors directly correlates with their immunoglobulin synthesis rates. Therefore, we hypothesized that normal plasma cells are also hypersensitive to proteasome inhibition owing to their extremely high amount of protein biosynthesis. Here we show that the proteasome inhibitor bortezomib, which is approved for the treatment of multiple myeloma, eliminates both short- and long-lived plasma cells by activation of the terminal unfolded protein response. Treatment with bortezomib depleted plasma cells producing antibodies to double-stranded DNA, eliminated autoantibody production, ameliorated glomerulonephritis and prolonged survival of two mouse strains with lupus-like disease, NZB/W F1 and MRL/lpr mice. Hence, the elimination of autoreactive plasma cells by proteasome inhibitors might represent a new treatment strategy for antibody-mediated diseases.
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PMID:The proteasome inhibitor bortezomib depletes plasma cells and protects mice with lupus-like disease from nephritis. 1854 49

The diagnosis of autoimmune hemolytic anemia (AIHA) relies mainly on the direct antiglobulin test (DAT), that is, Coombs' direct test, which has a sensitivity of about 95%. The classification of different forms of AIHA depends on the characteristics of the autoantibody and is an essential part of the diagnostic procedure. AIHAs mediated by warm-reactive autoantibodies (wAIHA) account for approximately 70% of all types: they may be either idiopathic or secondary to another autoimmune disorder (such as systemic lupus, lymphoma or primary immune deficiencies) or drug-induced. In adults, AIHA may also precede by many years the onset of non-Hodgkin lymphoma (NHL) or myelodysplastic syndrome. The management of wAIHA, based mainly on empirical data and uncontrolled studies, relies principally on corticosteroids as a first-line therapy. In cases of steroid resistance ( approximately 5-10% of the cases) and in cases of steroid-dependency, the most frequent second-line options are splenectomy or immunosuppressive agents. More recently, rituximab has shown promising results in small uncontrolled and retrospective studies and it is now widely used in refractory wAIHA. Future prospective studies should assess its efficacy earlier in the course of disease as a steroid-sparing strategy. Evans syndrome is an autoimmune disorder defined by the simultaneous or sequential combination of AIHA and immune thrombocytopenia or immune neutropenia. It may reveal an underlying condition (e.g., lupus, common variable immunodeficiency, etc.). Its management is usually extrapolated from the standard of care for isolated wAIHA. Before the availability of rituximab, the overall prognosis was relatively poor for adults with both wAIHA and ES, with a mortality rate of 15 to 20%.
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PMID:[Characteristics of warm autoimmune hemolytic anemia and Evans syndrome in adults]. 1864 24

The aetiology of systemic lupus erythematosus (SLE) is thought to involve both genetic and environmental factors. In other complex diseases, analysis of large multi-case families has resulted in insights into biological mechanisms. We have sought to characterise the members of an extended Indigenous family, five of whom have been diagnosed with SLE. Pedigree members were evaluated using the Lupus Screening Questionnaire, clinical interviews and medical records. Participants contributed blood and urine samples for laboratory analysis. A Mendelian pattern of inheritance was not observed. The five affected members (all female) shared two American College of Rheumatology criteria (positive ANA and arthritis) but showed a wide variety of other SLE manifestations. Disease onset, severity and progression were discordant. Including the five individuals with SLE, 15 blood relatives and two non-consanguineous spouses had autoimmune manifestations. Autoimmune haemolytic anaemia (one case), idiopathic thrombocytopenic purpura (ITP) (one case) and hypothyroidism (two cases) were observed in non-SLE affected individuals. Anti-nuclear antibodies were present in 12 blood relatives and one non-consanguineous spouse. Infections (especially of the skin) were observed to be common in the kindred. The lack of clear Mendelian inheritance or phenotypic concordance makes a rare monogenic explanation for SLE unlikely in this family. The finding of familial autoimmunity associated with SLE further supports the hypothesis that a common genetic pathway can precipitate autoimmunity, with further genes and possible environmental factors interacting to produce the eventual phenotype. Future genetic linkage studies may reveal a rare 'autoimmune gene' variant in this kindred.
Lupus 2009 Feb
PMID:The clinical characterisation of systemic lupus erythematosus in a Far North Queensland Indigenous kindred. 1915 Nov 16

Evans syndrome (ES) is a rare disease characterized by the simultaneous or sequential development of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) and/or immune neutropenia. To better describe the characteristics and outcome of ES in adults, a survey was initiated in 2005. The data from 68 patients (60% of them women) fulfilling strict inclusion criteria for ES are reported. The mean age at time of ITP and/or AIHA onset was 52 plus or minus 33 years, both cytopenias occurred simultaneously in 37 cases (54.5%). ES was considered as "primary" in 34 patients (50%) but was associated with an underlying disorder in half of the cases, including mainly systemic lupus, lymphoproliferative disorders, and common variable immunodeficiency. All patients were given corticosteroids, but 50 of them (73%) required at least one "second-line" treatment, including splenectomy(n = 19) and rituximab (n = 11). At time of analysis, after a mean follow-up of 4.8 years, only 22 patients (32%) were in remission off treatment; 16 (24%) had died. In elderly patients, the risk of cardiovascular manifestations related to AIHA seems to be higher than the ITP-related risk of severe bleeding. In conclusion, ES is a potentially life-threatening condition that may be associated with other underlying autoimmune or lymphoproliferative disorders.
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PMID:The spectrum of Evans syndrome in adults: new insight into the disease based on the analysis of 68 cases. 1963 26

Raltegravir is a recently, Food and Drug Administration-approved, small-molecule drug that inhibits retroviral integrase, thereby preventing HIV DNA from inserting itself into the human genome. We report here that the activity profile of raltegravir on the replication of murine leukemia virus is similar to that for HIV, and that the drug specifically affects autoimmune disease in mice, in which endogenous retroelements are suspected to play a role. While NZW and BALB/c mice, which do not succumb to autoimmune disease, are not affected by raltegravir, lupus-prone (NZBxNZW) F(1) mice die of glomerulonephritis more than a month earlier than untreated mice. Raltegravir-treated NZB mice, which share the H-2 haplotype with BALB/c mice, but which are predisposed to autoimmune hemolytic anemia, develop auto-antibodies to their red blood cells >3 months earlier than untreated mice of the same strain. Because nonautoimmune mice are not affected by raltegravir, we consider off-target effects unlikely and attribute the exacerbation of autoimmunity to the inhibition of retroviral integrase.
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PMID:Early onset of autoimmune disease by the retroviral integrase inhibitor raltegravir. 1992 37

Hematological disturbances are common in systemic lupus erythematous (SLE). Specifically, autoimmune hemolytic anemia (AHA) may manifest in SLE patients at the time of diagnosis or within the first year of the disease. AHA is often associated with thrombocytopenia, lupus nephritis, and central nervous system activity. In this study we investigated these associations in Brazilian patients with SLE. Forty-four consecutive SLE patients who had a history of AHA were age, gender, and disease duration matched with 318 SLE patients without AHA who formed the control group. All patients fulfilled the revised American College of Rheumatology criteria for SLE and were followed-up within our Service. Clinical and laboratorial manifestations were similar in both groups, except for the predominance of leukopenia, thrombocytopenia, and anti-dsDNA on univariate analysis in the AHA group. The multivariate logistic regression model revealed risk only for thrombocytopenia in the AHA group compared to the control group (odds ratio, 2.70; 95% confidence interval, 1.32-5.50). Our results corroborate previous data that AHA in SLE increases the risk of thrombocytopenia in individuals with SLE. This association suggests a common mechanism in AHA and SLE pathophysiologies.
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PMID:Autoimmune hemolytic anemia in systemic lupus erythematosus: association with thrombocytopenia. 2047 39

Autoimmune hemolytic anemia (AIHA) is a well known paraneoplastic phenomenon in lymphoproliferative disorders but there are also a number of case reports of such an association with solid tumors. We have analysed 52 cases of this association reported in the literature. We found that AIHA may occur prior to, concurrent with cancer or well after end of treatment, either as a sign of recurrence or in complete remission of the cancer. 70% of the patients had warm antibody and 30% cold antibody AIHA. Some patients had additional antibodies such as platelet antibodies (Evans syndrome), lupus anticoagulants or antibodies to C1 esterase inhibitor. AIHA occurred in almost all types of cancers, but it was relatively more common in renal cell cancer and Kaposi sarcoma compared to other cancers. In early stage cancers, in particular in renal cell cancers, curative resection of the cancers led to complete, often sustained remission of AIHA within a short time in a number of patients. Resection of the tumor had also beneficial effects in some metastatic cancers. Patients who had a response to resection of the tumor were often refractory to steroid treatment before surgery, while some responses to steroids were observed in patients with metastatic cancer. The study of cancer patients with autoimmune diseases may provide important insights into the biology of tumors.
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PMID:Autoimmune hemolytic anemia as a paraneoplastic phenomenon in solid tumors: A critical analysis of 52 cases reported in the literature. 2050 16


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