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)

Atopic dermatitis (AD) has a Th2 (T-helper 2) immune-reactivity pattern. However, the majority of systemic autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, and insulin dependent diabetes mellitus show a Th1 (T-helper 1) reactivity pattern. From this, one may hypothesize that AD and the Th1 autoimmune diseases could be inversely associated and AD may be more common in the minority of autoimmune diseases with a Th2 overactivity pattern such as systemic lupus erythematosus. A cross sectional study was designed. Our patients were enrolled from a general university hospital (all systemic autoimmune patients in every medical ward based on definite diagnoses in their medical records). Information on atopic dermatitis was obtained by questionnaires and physical examination by a dermatologist. A total of 63 patients were studied; 17.5 percent of cases had atopic dermatitis in the past or present. There were 31 patients 49.2 %) who carried a diagnosis known to be associated with Th1 reaction, and 21 patients (33.3 %) who had a disease associated with Th2-type reactivity. In 11 patients (17.5 %) the T-cell reaction type was not definitively classified. The relative frequency of AD was 9.7 percent (3 of 31 cases) in Th1-related autoimmune diseases, 28.6 percent (6 of 21 cases) in Th2-related autoimmune diseases and 18.2 percent (2 of 11 cases) in the unclassified category, a difference not statistically significant. Although the power of this study is not high enough to show a statistical significance, AD seems to be uncommon in patients with autoimmune diseases associated with Th1 overactivity.
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PMID:Atopic dermatitis and systemic autoimmune diseases: a descriptive cross sectional study. 1663 17

The aim of this study was to test whether the functional variant rs2076530 of the BTNL2 gene confers susceptibility to the autoimmune diseases type 1 diabetes (T1D), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Our study populations consisted of 326 patients with T1D and 351 healthy subjects, 808 patients with RA and 1137 healthy controls, and 372 patients with SLE and 280 healthy controls. Genotyping of the BTNL2 gene rs2076530 polymorphism was performed by real-time polymerase chain reaction technology, using the TaqMan 5'-allele discrimination assay. We observed statistically significant differences in the distribution of BTNL2rs2076530 alleles between patients with T1D, RA, and SLE and healthy controls (p=0.0035, 0.000003, and 0.00002, respectively), but in two divergent ways: the G allele was associated with T1D and RA, and the A allele was associated with SLE. However, the polymorphism exhibited strong linkage disequilibrium with HLA DQB1-DRB1 haplotypes previously identified as predisposing to the diseases. When the BTNL2 polymorphism was tested conditional on HLA DQB1-DRB1haplotypes, the BTNL2 effect was no longer significant in all three study populations. The BTNL2 rs2076530 polymorphism is associated with T1D, RA, and SLE because of its strong linkage disequalibrium with predisposing HLA DQB1-DRB1 haplotypes in Caucasian populations.
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PMID:Analysis of a functional BTNL2 polymorphism in type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus. 1669 Apr 10

We recently discovered that a single-nucleotide polymorphism (SNP) in the lymphoid tyrosine phosphatase (LYP), encoded by the PTPN22 gene on chromosome 1p13, correlates strongly with the incidence of type 1 diabetes (T1D) in two independent populations. This findings has now been verified by numerous studies and it has been expanded to rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus, Graves' disease, generalized vitiligo and other autoimmune disease. Here we review the genetics of the SNP and its association with autoimmunity, discuss the function of the phosphatase in signaling, the biochemistry of the disease-predisposing allele, and the possible mechanisms by which PTPN22 contributes to the development of human disease.
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PMID:Role of PTPN22 in type 1 diabetes and other autoimmune diseases. 1669 61

It is now well accepted that interferon (IFN)alpha plays a critical role in the pathogenesis and perpetuation of specific autoimmune diseases, including systemic lupus erythematosus (SLE), autoimmune thyroid disease and type 1 diabetes. IFNalpha-based treatments are widely used for the treatment of chronic viral infections, particularly chronic hepatitis C virus infection; however, several case reports have emerged describing autoimmune conditions that have developed during IFNalpha therapy. The data support the pathogenic potential of IFNalpha in autoimmunity, although it is clear that genetic and environmental factors are also key to the development of autoimmune conditions. Several points of interaction between IFNalpha and immune effector cells have been experimentally defined, the functional consequences of many of which remain poorly understood. This review describes the most recent data in support of an important role for IFNalpha in autoimmunity, particularly SLE, and the potential mechanisms by which IFNalpha contributes to immune dysfunction. Future approaches to IFNalpha modulation as a therapeutic strategy for use in the treatment of autoimmune diseases are also discussed.
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PMID:Interferon alpha and its contribution to autoimmunity. 1672 22

Three very recent reports provide convincing statistical evidence (P < 10(-8)), at a genome-wide level, of the association of common polymorphisms with three different common diseases: systemic lupus erythematosus (IRF5), prostate cancer and type 1 diabetes (IFIH1 region). This adds to the trickle--soon to be a flood--of disease association results that are highly unlikely to be false positives. There are other convincing examples in the last 12 months: age-related macular degeneration (CFH), type 1 diabetes (IL2RA, also known as CD25) and type 2 diabetes (TCF7L2). Given 20 years of a literature full of irreproducible results, what has changed?
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PMID:Statistical false positive or true disease pathway? 1732 72

The capacity to locate polymorphisms on a virtually complete map of the human genome coupled with the ability to accurately evaluate large numbers (by historical standards) of genetic markers has led to gene identification in complex diseases, such as systemic lupus erythematosus (SLE or lupus). While this is a phenotype with enormous clinical variation, the twin studies and the observed familial aggregation, along with the genetic effects now known, suggest a strong genetic component. Unlike type 1 diabetes, lupus genetics is not dominated by the powerful effect of a single locus. Instead, there are at least six known genetic association effects in lupus of smaller magnitude (odds ratio <2), and at least 17 robust linkages (established and arguably confirmed independently) defining potentially responsible genes that largely remain to be discovered. The more convincing genetic associations include the human leukocyte antigen region (with multiple genes), C1q, PTPN22, PDCD1, Fc receptor-like 3, FcgammaRIIA, FcgammaRIIIA, interferon regulatory factor 5, and others. How they contribute to disease risk remains yet to be clarified, beyond the obvious speculation derived from what has previously been learned about these genes. Certainly, they are expected to contribute to lupus risk independently and in combination with each other, with genes not yet identified, and with the environment. A substantial number of genes (>10) are expected to be identified to contribute to lupus or in its many subsets defined by clinical and laboratory features.
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PMID:Unraveling the genetics of systemic lupus erythematosus. 1702 21

Regulatory T-cells CD4+CD25+Foxp3, possessing suppressory activity, play the key role in the development of autoimmune diseases, maintenance of peripheral tolerance in transplantation immunity, and the prevention of a pathological immune response to intestinal microflora or microbial infection. A decrease in the total number of circulating CD4+CD25+ regulatory T-cells and their suppressive activity have been found in patients suffering from various autoimmune diseases, such as type 1 diabetes, multiple sclerosis, autoimmune hepatitis, psoriatic arthritis, juvenile idiopathic arthritis, and systemic lupus erythematosus (SLE). The authors of this study investigated the phenotypic characteristics of peripheral blood lymphocytes in 31 SLE patients and the effect of treatment on the content of CD4+CD25+ T-cells before and after pulse therapy with methylprednisolone and cyclophosphan. The total number of regulatory T-cells in the group of untreated patients was almost twice lower vs. the group of healthy donors. As a result of the therapy, the proportion of regulatory T-cells increased significantly, although it did not reach the values in the control group. The data from this research confirm the development of a defect of CD4+CD25+ T-cells at the active phase of SLE, and a possibility to partially correct this defect with an effective therapy.
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PMID:[The role of regulatory T-cells in autoimmune rheumatic diseases]. 1711 29

Invariant NKT cells play a critical role in controlling the strength and character of adaptive immune responses. We have previously reported deficiencies in the numbers and function of NKT cells in the NOD mouse strain, which is a well-validated model of type 1 diabetes and systemic lupus erythematosus. Genetic control of thymic NKT cell numbers was mapped to two linkage regions: Nkt1 on distal chromosome 1 and Nkt2 on chromosome 2. In this study, we report the production and characterization of a NOD.Nkrp1(b).Nkt1(b) congenic mouse strain, apply microarray expression analyses to limit candidate genes within the 95% confidence region, identify Slamf1 (encoding signaling lymphocyte activation molecule) and Slamf6 (encoding Ly108) as potential candidates, and demonstrate retarded signaling lymphocyte activation molecule expression during T cell development of NOD mice, resulting in reduced expression at the CD4(+)CD8(+) stage, which is consistent with decreased NKT cell production and deranged tolerance induction in NOD mice.
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PMID:Slamf1, the NKT cell control gene Nkt1. 1723 11

The PTPN22 gene, encoding the lymphoid-specific protein tyrosine phosphatase, a negative regulator in the T-cell activation and development, has been associated with the susceptibility to several autoimmune diseases, including type 1 diabetes. Based on combined case-control and family-based association studies, we replicated the finding of an association of the PTPN22 C1858T (R620W) functional variant with type 1 diabetes, which was independent from the susceptibility status at the insulin gene and at HLA-DR (DR3/4 compared with others). The risk contributed by the 1858T allele was increased in patients with a family history of other autoimmune diseases, further supporting a general role for this variant on autoimmunity. In addition, we found evidence for an association of 1858T allele with the presence of GAD autoantibodies (GADA), which was restricted to patients with long disease duration (>10 years, P < 0.001). This may help define a subgroup of patients with long-term persistence of GADA. The risk conferred by 1858T allele on GAD positivity was additive, and our meta-analysis also supported an additive rather than dominant effect of this variant on type 1 diabetes, similar to previous reports on rheumatoid arthritis and systemic lupus erythematosus.
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PMID:PTPN22 R620W functional variant in type 1 diabetes and autoimmunity related traits. 1725 1

My lab investigates genetic control of autoimmune disease and autoimmune phenotypes using a series of nonobese diabetic (NOD) congenic mice. NOD congenic mice have regions from B6/B10 introgressed onto the NOD genetic background, which reduces the severity/incidence of autoimmune diabetes. We have demonstrated, however, that while diabetes is reduced, other autoimmune phenotypes and diseases arise in NOD congenic mice. Mapping the genomic regions responsible for these phenotypes has produced novel insights into genetic control of autoimmunity. This review will illustrate some of the genetically controlled phenotypes we have investigated, which shed light upon autoimmune features relevant to human type 1 diabetes, systemic lupus erythematosus, and primary biliary cirrhosis.
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PMID:Dissecting genetic control of autoimmunity in NOD congenic mice. 1733 79


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