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)

Autoantibodies to the recombinant extracellular domain of epidermal growth factor receptor (exEGFR) were detected by ELISA in the serum of Fas-defective old MRL/MpJ/lpr and C3H/HeJ/gld mice, but not young mice from these strains, or nonautoimmune young and old BALB/c, MRL/MpJ/++, and C3H/HeJ/MMTV mice. Compared with control human subjects without autoimmune disease, the frequency of exEGFR-binding autoantibodies was increased in scleroderma (systemic sclerosis) patients and to a lesser extent in lupus patients. Phage autoantibodies (Fv fragments) isolated from a lupus library by selection on a linear epitope of EGFR (residues 294-310) displayed the ability to bind exEGFR. Treatment of EGFR-expressing A431 cells with autoantibodies purified by affinity chromatography on immobilized exEGFR resulted in specific staining of the cells. Short-lived but strong inhibition of cellular DNA synthesis was observed in the presence of the autoantibodies. We concluded that autoantibody responses to EGFR hold the potential of fulfilling a pathogenic role in autoimmune disease.
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PMID:Autoantibodies to the epidermal growth factor receptor in systemic sclerosis, lupus, and autoimmune mice. 1255 92

The purpose of this study was to determine if epidermal growth factor receptor (EGFR) gene polymorphism was a marker of susceptibility to or severity of Chinese patients with systemic lupus erythematosus (SLE) in Taiwan. The study included 119 Chinese patients with SLE. One hundred unrelated healthy individuals living in central Taiwan served as control subjects. Polymorphisms of the EGFR Bsr I gene were typed from genomic DNA. The genotypes, allelic frequencies and carriage rates were compared between SLE patients and control subjects. The relationship between allelic frequencies and clinical manifestations of SLE was evaluated. For the genotype of EGFR gene Bsr I polymorphism, there was statistically significant differences between the SLE and control groups (chi-squared test, P = 0.009, chi2 = 9.21). In addition, there was significant association between the two groups in allelic frequency of the T allele (P = 0.02, chi2 = 5.27). However, we did not detect any association between EGFR genotype and clinical or laboratory profiles in SLE patients. The results suggest that the EGFR gene Bsr I polymorphism is related to SLE.
Lupus 2004
PMID:Epidermal growth factor receptor (EGFR) gene Bsr I polymorphism is associated with systemic lupus erythematosus. 1554 May 9

Bz-423 is a new benzodiazepine that has cytotoxic and cytostatic effects against a number of cell types in culture, and recent studies have shown efficacy in experimental lupus models in rodents. The present study demonstrates that treating human skin in organ culture with Bz-423 suppresses retinoid-induced epidermal hyperplasia. Bz-423 suppresses hyperplasia in organ culture at concentrations that also inhibit keratinocyte proliferation in monolayer culture but that are not cytotoxic for keratinocytes and do not inhibit fibroblast growth. Under conditions in which keratinocyte proliferation is inhibited, there is no measurable effect on epidermal growth factor receptor activation, but there is reduced signaling at the level of extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase. Suppression of keratinocyte growth by Bz-423 is associated with generation of intracellular oxidants. However, antioxidant treatment reduces keratinocyte cytotoxicity that occurs at high concentrations of Bz-423, but it does not inhibit growth suppression. Together, these data suggest that Bz-423 has the potential to limit the untoward effects associated with topical retinoid treatment, and in addition, may have therapeutic effects against other forms of epidermal hyperplasia.
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PMID:A novel benzodiazepine selectively inhibits keratinocyte proliferation and reduces retinoid-induced epidermal hyperplasia in organ-cultured human skin. 1557 71

Three women with known breast cancer presented with very similar annular erythemas of their chest walls. All women were in remission from their breast cancer for at least 6 months. Their breast cancers had initially responded well to multi-modality treatment with no clinical or radiologic evidence of recurrence, until the development of the annular erythema. In the first case, the annular erythema was treated unsuccessfully as a dermatitis and then as tinea corporis. In the second case, subacute cutaneous lupus was considered but lupus antibodies were negative. In the third case, the annular erythema was promptly recognized and biopsied. Histology in all three cases revealed identical findings of invasive ductal carcinoma involving the lymphatics of the skin. Immunohistochemical staining of the carcinoma was positive for human epidermal growth factor receptor 2 but negative for oestrogen and progesterone receptors. Annular erythema can pose a wide differential but rarely has it been described as a sign of locally recurrent cancer. These cases highlight the importance of recognizing this entity in the oncologic patient, where prompt skin biopsies can confirm the diagnosis and allow early initiation of therapy.
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PMID:Annular erythema as a sign of recurrent breast cancer. 2054 22

Chemotherapy and its cutaneous side effects are an increasingly common source of iatrogenic injury to the skin, hair, and nails. Cutaneous changes are among the most common side effects from treatment with particular targeted chemotherapeutic agents, especially those that target the epidermal growth factor receptor and small molecule multikinase inhibitors. Less common, but growing in recognition, are the development of secondary cutaneous neoplasms and subacute cutaneous lupus erythematosus as a result of chemotherapy. There is considerable overlap of the multiple entities described as a side effect from conventional chemotherapeutic agents; therefore, the term "toxic erythema of chemotherapy" can be used as an easily understood name.
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PMID:Chemotherapy-induced iatrogenic injury of skin: new drugs and new concepts. 2201 81

Histologically, drug eruptions may present virtually all patterns of inflammation in the skin, including spongiotic, lichenoid and psoriasiform dermatitis as well as vasculitis or panniculitis. Drug reactions may mimic specific skin diseases such as lupus erythematosus, lichen planus or lymphoma. While a single drug may cause a wide range of reaction patterns, no reaction pattern is specific for a certain drug. Nevertheless, some reactions are quite characteristic for certain drugs as for example psoriasiform dermatitis for anti-TNF agents or folliculitis for epidermal growth factor receptor antagonists. Heightened awareness to the possible mimicry of other skin diseases as well as integration of clinical data is pivotal for the appropriate histological diagnosis of drug reactions in the skin. For practical reasons and in the aim of helping clinicians, the different drug reactions described in this chapter are classified according to the main histological reaction pattern present. Nevertheless, this classification may be somewhat artificial in some cases as drug reactions often reveal a coexistence of different reaction patterns.
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PMID:Histopathological patterns indicative of distinct adverse drug reactions. 2261 54

Photosensitivity, or skin sensitivity to ultraviolet radiation (UVR), is a feature of lupus erythematosus and other autoimmune and dermatologic conditions, but the mechanistic underpinnings are poorly understood. We identify a Langerhans cell (LC)-keratinocyte axis that limits UVR-induced keratinocyte apoptosis and skin injury via keratinocyte epidermal growth factor receptor (EGFR) stimulation. We show that the absence of LCs in Langerin-diphtheria toxin subunit A (DTA) mice leads to photosensitivity and that, in vitro, mouse and human LCs can directly protect keratinocytes from UVR-induced apoptosis. LCs express EGFR ligands and a disintegrin and metalloprotease 17 (ADAM17), the metalloprotease that activates EGFR ligands. Deletion of ADAM17 from LCs leads to photosensitivity, and UVR induces LC ADAM17 activation and generation of soluble active EGFR ligands, suggesting that LCs protect by providing activated EGFR ligands to keratinocytes. Photosensitive systemic lupus erythematosus (SLE) models and human SLE skin show reduced epidermal EGFR phosphorylation and LC defects, and a topical EGFR ligand reduces photosensitivity. Together, our data establish a direct tissue-protective function for LCs, reveal a mechanistic basis for photosensitivity, and suggest EGFR stimulation as a treatment for photosensitivity in lupus erythematosus and potentially other autoimmune and dermatologic conditions.
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PMID:A protective Langerhans cell-keratinocyte axis that is dysfunctional in photosensitivity. 3011 46