Clinical Expression Of Systemic Lupus Erythematosus Research Articles

Prolactin has a pathogenic role in systemic lupus erythematosus

Prolactin, a 23-kDa peptide hormone, is produced by the anterior pituitary gland and extrapituitary sites including the immune cells. Prolactin (PRL) participates in innate and adaptive immune response. PRL stimulates the immune cells by binding to receptor (PRL-R). Binding of PRL to its receptor activates the Janus kinase-signal transducer (JAK-STAT). Activation of these cascades results in endpoints such as immunoestimulator and immunosupressor action. Prolactin belongs to the network of immune-neuroendocrine interaction. Hyperprolactinemia has been found in patients with systemic lupus erythematosus (SLE), and new evidence has confirmed a significant correlation between serum PRL levels and disease activity. PRL participates in activation of SLE during pregnancy and in pathogenesis of lupus nephritis, neuropsychiatric, serosal, hematologic, articular, and cutaneous involvement. Hyperprolactinemia was associated with increase IgG concentrations, anti-DNA antibodies, immune complex, glomerulonephritis, and accelerated mortality in murine lupus. Bromocriptine, a dopamine analog that suppresses PRL secretion, was associated with decreased lupus activity, prolonged lifespan, and restoration of immune competence in experimental model. In clinical trials, bromocriptine and derivative drugs showed beneficial therapeutic effect in treating human lupus, including pregnancy. Taken together, clinical and experimental results leave little doubt that PRL indeed contributes to the pathogenesis and clinical expression of SLE.

Genetic polymorphisms of glutathione S-transferases and cytochrome P450 enzymes as susceptibility factors to systemic lupus erythematosus in southern Brazilian patients.

Systemic lupus erythematosus (SLE) is an autoimmune chronic inflammatory disease that presents several clinical manifestations, affecting multiple organs and systems. Immunological, environmental, hormonal and genetic factors may contribute to disease. Genes and proteins involved in metabolism and detoxification of xenobiotics are often used as susceptibility markers to diseases with environmental risk factors. Cytochrome P450 (CYP) enzymes activate the xenobiotic making it more reactive, while the Glutathione S-transferases (GST) enzymes conjugate the reduced glutathione with electrophilic compounds, facilitating the toxic products excretion. CYP and GST polymorphisms can alter the expression and catalytic activity of enzymes. This study aimed to investigate the role of genetic variants of CYP and GST in susceptibility and clinical expression of SLE, through the analysis of GSTM1 null, GSTT1 null, GSTP1*Ile105Val, CYP1A1*2C and CYP2E1*5B polymorphisms. 371 SLE patients from Hospital de Clínicas de Porto Alegre and 522 healthy blood donors from southern Brazil were evaluated. GSTP1 and CYP variants were genotyped using PCR-RFLP and GSTT1 and GSTM1 variants were analyzed by multiplex PCR. Among European-derived individuals, a lower frequency of GSTP1*Val heterozygous genotypes was found in SLE patients when compared to controls (p = 0.005). In African-derived SLE patients, the CYP2E1*5B allelic frequency was higher in relation to controls (p = 0.054). We did not observe any clinical implication of the CYP and GST polymorphisms in patients with SLE. Our data suggest a protective role of the GSTP1*Ile/Val heterozygous genotype against the SLE in European-derived and a possible influence of the CYP2E1*5B allele in SLE susceptibility among African-derived individuals.

Influence of Hormonal Events on Disease Expression in Patients with the Combination of Systemic Lupus Erythematosus and Rheumatoid Arthritis

The concurrent presence of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) ("rhupus" or "rufus") has been described in the literature. However, it has not been clear to what extent and under what circumstances clinical disease expresssion can undergo transitions from one disease to the other. We postulated that major hormonal events might have an influence on disease expression in such patients and conducted a retrospective study of 1507 patients with RA and 893 with SLE. In this population, 13 patients were identified as having convincing clinical diagnoses of both RA and SLE. Although 6 of these 13 patients had symptoms and signs of RA and SLE concurrently during their entire illness, 7 patients had clearly identifiable transitions from SLE to RA, and in one of these patients the reverse occurred as well. Of the 7 transitions from SLE to RA, 5 were associated with menopause (3 of these patients were receiving hormone replacement therapy) and the other 2 occurred in the postpartum period. The one change from RA to SLE in this series occurred during pregnancy. Thus, pregnancy, the postpartum period, and menopause can modulate disease expression in patients with both SLE and RA. It is speculated that, in patients with an autoimmune predilection, a high-estrogen environment (premenopause, pregnancy) favors the clinical expression of SLE, whereas a low-estrogen environment favors more RA-like disease, possibly because of the immunomodulatory effects of sex-steroids. The clinical implication is that in the management of patients with autoimmune diseases such as SLE and RA, hormonal alterations could result in changes in disease expression that might necessitate changes in treatment.

Ethnic differences in the clinical expression of systemic lupus erythematosus: A comparative study between African-Americans and Latin Americans

Since ethnic differences in the disease expression of systemic lupus erythematosus (SLE) have been recognized, we compared the clinical and serological features in two different ethnic groups of patients with SLE. The study population consisted of 222 African-American and 300 Latin American (Colombian) SLE patients. Clinical, demographic, and laboratory data were obtained by chart review using a standard data collection form. African-American patients more commonly manifested discoid skin lesions, pulmonary fibrosis, and pleuritis, and less commonly manifested photosensitivity, livedo reticularis, and vascular thrombosis than did Latin Americans. In addition, there was a higher frequency of anti-Sm, anti-RNP, and anti-Ro positivity among African-American patients compared with Latin Americans. These results are additional evidence for the presence of ethnic differences in the clinical expression of SLE.

Immunoglobulin allotypes are not associated with HLA-antigens, autoantibodies and clinical symptoms in systemic lupus erythematosus

Immunoglobulin heavy chain (G1m, G2m, G3m, A2m) and kappa light chain (Km) allotype and phenotype frequencies of 323 central European Caucasian patients with systemic lupus erythematosus (SLE) were examined and correlated with various genetic, serologic and clinical markers of SLE. No significant associations were found between immunoglobulin allotypes or phenotypes and all 20 parameters tested (nephritis, vasculitis, arthralgias, photosensitivity, discoid lesions, central nervous system disease, Raynaud's phenomenon, sex, anti-Ro, anti-La, anti-nRNP, HLA-DR1-DR7, HLA phenotypes B8-DR3, B7-DR2). It could therefore be assumed that Gm, A2m and Km allotypes were not associated with HLA-antigens and had no influence on the serologic and clinical expression of SLE.

Systemic Lupus Erythematosus in the Elderly

Nine of 86 patients with systemic lupus erythematosus (SLE) were diagnosed after the age of sixty. They differ from younger patients with SLE in mode of onset, specific organ systems involved, severity of disease, and prognosis. The presentation in the elderly is insidious rather than acute. Most patients initially show a polymyalgia rheumatica syndrome or rheumatoid-like arthritis. The clinical course is benign, serositis is less common, the patients are more easily controlled on aspirin or low-dose steroids, and the progress of SLE in the elderly is relatively slow. Because age modifies the clinical expression of SLE the diagnosis in the elderly can be easily missed if not specifically searched for.