Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Etanercept may play an important role in modulating the inflammatory activity and progression of human immunodeficiency virus (HIV)-associated psoriasis and psoriatic arthritis. We report the case of a 45-year-old homosexual man with a CD4 cell count of less than 0.05 x 10(9)/L and an HIV viral load of 4200 copies/mL (while receiving highly active antiretroviral therapy) who developed extensive psoriatic plaques, 4.5-kg weight loss, onychodystrophy, and psoriatic arthropathy with severe periarticular bone demineralization. The arthritis progressed despite the use of several disease-modifying medications, including corticosteroids, hydroxychloroquine, and minocycline. Because of uncontrolled, progressive, and disabling arthritis and resulting profound disability, he was treated with etanercept. Within 3 weeks, his psoriasis had improved dramatically and his joint inflammation had stabilized. For the next 4 months, immunologic and viral parameters remained stable, but his clinical course was complicated by frequent polymicrobial infections. Etanercept was thus discontinued despite continued improvements in his psoriasis, psoriatic arthritis, and functional status. While both cutaneous and joint manifestations of psoriasis improved dramatically, the experience with this patient dictates that caution and careful follow-up must be exercised when prescribing etanercept in the setting of HIV infection.
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PMID:Etanercept for the treatment of human immunodeficiency virus-associated psoriatic arthritis. 1104 Aug 59

Autoimmunity can develop from an often undetermined interplay of genetic and environmental factors. Rare forms of autoimmune conditions may also result from single gene mutations as for autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, an autosomal recessive disease associated with mutated forms of the autoimmune regulator gene. It was proposed that genetic variability in the autoimmune regulator locus, in particular heterozygous loss-of-function mutations, might favor the development of organ-specific autoimmunity by affecting the presentation of self-antigens in the thymus. Indeed, heterozygous mutations of the autoimmune regulator gene were reported in patients with organ-specific autoimmunity. Also, in primary immunodeficiencies, a breakdown in central/peripheral tolerance frequently produces association with autoimmunity. The causative link may involve a common genetic background and several gene defects have been identified as putative culprits. We report a unique patient, a 14 year old male from Lazio region, affected by common variable immunodeficiency associated with autoimmune manifestations (alopecia, onychodystrophy) and heterozygote for the S250C variant located in the SAND domain of the autoimmune regulator gene protein. To our knowledge this is the first report of the S250C variant in a patient bearing this unusual combination of autoimmunity and immunodeficiency. To obtain insights into the possible molecular effects of the S250C variant, we have carried out an in silico analysis of the SAND domain structure of the autoimmune regulator protein. In particular, homology modeling has allowed us to observe that the cysteine introduced by the S250C variant is surrounded by cationic residues, and by means of molecular dynamics simulations together with pKa calculations, we have shown that these residues remain stably proximal to cysteine-250 lowering its pKa and thus conferring high chemical reactivity to the mutated residue. We propose that the enhanced reactivity of cysteine-250, which is likely to impair the protein function but probably insufficient to produce alone a phenotype as a heterozygous S250C variant due to compensation mechanisms, might become manifest when combined with other genetic/environmental factors. These results can provide the rationale for the patient's unusual phenotype, shedding new light into the pathogenesis of the clinical association of autoimmunity and immunodeficiency.
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PMID:The possible implication of the S250C variant of the autoimmune regulator protein in a patient with autoimmunity and immunodeficiency: in silico analysis suggests a molecular pathogenic mechanism for the variant. 2506 7

Dermatophytosis in individuals with human immunodeficiency virus infection seems to manifest with atypical, multiple, or extensive lesions more frequently. In addition, there are reports of presentations with little inflammation, called anergics. Less common etiologic agents have been isolated in these individuals, such as Microsporum species. To describe clinical aspects and etiologic agents of dermatophytosis in individuals with human immunodeficiency virus (HIV) infection. Patients with clinical diagnosis of dermatophytosis underwent scarification for mycological diagnosis through direct microscopic examination and fungal isolation in culture on Sabouraud dextrose agar. Sixty individuals had a clinical hypothesis of dermatophytosis. In 20 (33.3%) of the 60 patients, dermatophytosis was confirmed through a mycological study. Tinea corporis, diagnosed in 14 patients, was the most frequent clinical form, followed by tinea unguium in 7, tinea cruris in 5, and tinea pedis in 1 patient. Most of the lesions of tinea corporis were anergic. Five patients with tinea unguium had involvement of multiple nails, with onychodystrophy as the predominant subtype. Multiple cutaneous lesions occurred in 3 patients and extensive cutaneous lesions in 4. Regarding the agent, Trichophyton rubrum was the most commonly isolated. The high occurrence of anergic skin lesions and involvement of multiple nails, especially as onychodystrophy, corroborates the hypothesis that atypical, disseminated, and more severe presentations are common in individuals with HIV infection. However, no Microsporum species was isolated even in atypical, extensive, or disseminated cases, in disagreement with previous reports. Therefore, the approach of squamous lesions in HIV-positive patients must include a mycological study, in view of the possibility of anergic dermatophytosis, to promote the introduction of a suitable therapeutic agent.
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PMID:Dermatophytosis in patients with human immunodeficiency virus infection: clinical aspects and etiologic agents. 2620 Jul 86