P-glycoprotein in autoimmune rheumatic diseases.

P-glycoprotein (Pgp) is a transmembrane protein of 170 kD encoded by the multidrug resistance 1 (MDR-1) gene, localized on chromosome 7. More than 50 polymorphisms of the MDR-1 gene have been described; a subset of these has been shown to play a pathophysiological role in the development of inflammatory bowel disease, femoral head osteonecrosis induced by steroids, lung cancer and renal epithelial tumors. Polymorphisms that have a protective effect on the development of conditions such as Parkinson disease have also been identified. P-glycoprotein belongs to the adenosine triphosphate binding cassette transporter superfamily and its structure comprises a chain of approximately 1280 aminoacid residues with an N-C terminal structure, arranged as 2 homologous halves, each of which has 6 transmembrane segments, with a total of 12 segments with 2 cytoplasmic nucleotide binding domains. Many cytokines like interleukin 2 and tumor necrosis factor alpha increase Pgp expression and activity. Pgp functions as an efflux pump for a variety of toxins in order to protect particular organs and tissues as the central nervous system. Pgp transports a variety of substrates including glucocorticoids while other drugs such as tacrolimus and cyclosporine A act as modulators of this protein. The most widely used method to measure Pgp activity is flow cytometry using naturally fluorescent substrates such as anthracyclines or rhodamine 123. The study of drug resistance and its association to Pgp began with the study of resistance to chemotherapy in the treatment of cancer and antiretroviral therapy for human immunodeficiency virus; however, the role of Pgp in the treatment of systemic lupus erythematosus, rheumatoid arthritis and psoriatic arthritis has been a focus of study lately and has emerged as an important mechanism by which treatment failure occurs. The present review analyzes the role of Pgp in these autoimmune diseases.

Comparative analysis of subacute cutaneous lupus erythematosus and chronic cutaneous lupus erythematosus: clinical and immunological study of 270 patients.

Background Lupus erythematosus (LE) is a chronic, autoimmune disease resulting from an interaction of genetic, environmental and hormonal factors and characterized by a spectrum of clinical forms with variable evolution from a localized cutaneous form to a life-threatening systemic form. Objective To analyse and compare the prevalence and characteristics of the main clinical and immunological manifestations of subacute cutaneous LE (SCLE) and chronic CLE (CCLE). Methods A total of 270 patients with CLE (112 patients with SCLE and 158 patients with CCLE) were studied retrospectively. The clinical and serological characteristics of all the patients were collected in a chart review. Results The patients with SCLE had a higher prevalence of annular and papulosquamous lesions, Raynaud phenomenon, mucous membrane ulcers, malar rashes, photosensitivity, vasculitis and a lower frequency of discoid lesions and alopecia compared with patients with CCLE. Patients with SCLE had a higher prevalence of arthralgias (P < 0.001), xerophthalmia (P = 0.045), arthritis (P < 0.001), nephropathy (P = 0.003) and systemic LE (SLE) (P < 0.001) compared with patients with CCLE. Patients with SCLE also had a higher frequency of laboratory and serological abnormalities than patients with CCLE. Generalized discoid LE (DLE) was associated with a higher prevalence of photosensitivity (P < 0.001), panniculitis (P = 0.009) and SLE (P = 0.003) than localized DLE. In patients with SCLE and those with CCLE, photosensitivity, arthralgias, arthritis, nephropathy and xerophthalmia were associated with SLE. In patients with SCLE, significant correlations existed between clinical and immunological data. Conclusions In our series, differences in the expression of CCLE and SCLE were found with respect to the distribution and type of lesions, systemic features and immunological findings.

Cutaneous lupus erythematosus: clinical and immunological study of 308 patients stratified by gender.

BACKGROUND: Numerous studies involving systemic lupus erythematosus (SLE) have attempted to identify gender differences in patients with lupus erythematosus (LE). However, few reports on cutaneous lupus erythematous (CLE) have identified gender differences. AIM: To analyse and compare the prevalence and characteristics of the main clinical and immunological features of male and female patients with CLE. METHODS: The medical records of 103 (33.4%) male and 205 (66.6%) female patients with CLE who were treated as inpatients or outpatients between January 1985 and December 2000 were retrospectively studied. All patients were reviewed in detail stratified by a predefined protocol. RESULTS: Female patients had a higher prevalence of Raynaud's phenomenon (P < 0.01), chilblain lupus (P = 0.005), arthralgias (P = 0.001) and SLE (P < 0.01). Female patients were also more likely to have an increased erythrocyte sedimentation rate (P < 0.005), higher levels of antinuclear antibodies (P < 0.001) and decreased levels of C3 (P < 0.001), C4 (P < 0.01) and CH50 (P < 0.01). There was a higher prevalence of clinical and laboratory abnormalities in female patients who had both SLE and CLE than in male patients with both conditions. Conclusions. In our series, differences in the expression of CLE existed between male and female patients with respect to the type of lesions, systemic features, and immunological findings.