ABSTRACT
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ABSTRACT
About 90% of patients with systemic lupus erythematosus (SLE) are female. We hypothesize that the number of X chromosomes, not sex, is a determinate of risk of SLE. Number of X chromosomes was determined by single nucleotide typing and then confirmed by karyotype or fluorescent in situ hybridization in a large group of men with SLE. Presence of an sry gene was assessed by RT-PCR. We calculated 96% confidence intervals using the Adjusted Wald method, and used Bayes' theorem to estimate the prevalence of SLE among 47,XXY and 46,XX men. Among 316 men with SLE, 7 had 47,XXY and 1 had 46,XX. The rate of Klinefelter's syndrome (47,XXY) was statistically different from that found in control men and from the known prevalence in the population. The 46,XX man had an sry gene, which encodes the testes determining factor, on an X chromosome as a result of an abnormal crossover during meiosis. In the case of 46,XX, 1 of 316 was statistically different from the known population prevalence of 1 in 20,000 live male births. A previously reported 46,XX man with SLE had a different molecular mechanism in which there were no common gene copy number abnormalities with our patient. Thus, men with SLE are enriched for conditions with additional X chromosomes. Especially since 46,XX men are generally normal males, except for infertility, these data suggest the number of X chromosomes, not phenotypic sex, is responsible for the sex-bias of SLE.
Subject(s)
Aneuploidy , Lupus Erythematosus, Systemic/genetics , Sex Chromosome Aberrations , Chromosomes, Human, X , Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+)/genetics , Humans , Male , Polymorphism, Single Nucleotide , Receptors, Androgen/genetics , Sex Factors , Sex-Determining Region Y Protein/geneticsABSTRACT
AIM: To determine the rate of Klinefelter's syndrome among men with systemic lupus erythematosus (SLE), and to determine whether the manifestations of SLE in these men are different from that seen in 46,XY men. METHODS: A total of 276 men with SLE underwent a real-time PCR procedure to screen for more than one X chromosome. Those with results consistent with two X chromosomes were further characterized by karyotype and FISH. Clinical manifestations of SLE were determined by interview, questionnaire and medical chart review. Each man with Klinefelter's and SLE was matched to four 46,XY men with SLE. Rates of SLE manifestations were compared with chi-square analyses. RESULTS: We found seven of the 286 men with SLE had Klinefelter's syndrome. Four of these seven were nonmosaic 47,XXY, while two were mosaic 46,XY/47,XXY and one was 46,XX/47,XXY. The men with 47,XXY did not have severe manifestations of SLE including no proliferative renal disease, neurological disease, thrombocytopenia, autoimmune haemolytic anaemia, discoid skin disease or anti-RNP/Sm. CONCLUSION: 47,XXY is found in excess among men with SLE. Men commonly have SLE that is more severe than that found among women, but the 47,XXY men had less severe SLE than other men.
Subject(s)
Klinefelter Syndrome/epidemiology , Lupus Erythematosus, Systemic/epidemiology , Humans , Klinefelter Syndrome/complications , Klinefelter Syndrome/genetics , Lupus Erythematosus, Systemic/complications , Male , Mosaicism , Severity of Illness IndexABSTRACT
Despite its overall simplicity, protein blotting or Western blotting has been proven to be a powerful procedure for the immunodetection of proteins, especially those that are of low abundance, following electrophoresis. The usefulness of this procedure stems from its ability to provide simultaneous resolution of multiple immunogenic antigens within a sample for detection by specific antibodies. Protein blotting has evolved greatly since its inception and researchers have a variety of ways and means to carry out this transfer. This procedure is used in combination with other important antibody-based detection methods such as enzyme-linked immunosorbant assay and immunohistochemistry to provide confirmation of results both in research and diagnostic testing. Specificity of antibodies used for immunohistochemistry is of critical importance and therefore Western blot is a "must" to address antibodies' specificity.
Subject(s)
Antibodies/isolation & purification , Antibody Specificity , Blotting, Western/methods , Immunohistochemistry/methods , Proteins/isolation & purification , Animals , Antibodies/immunology , Blotting, Western/instrumentation , Electrophoresis, Polyacrylamide Gel/instrumentation , Electrophoresis, Polyacrylamide Gel/methods , Equipment Design , Humans , Immunohistochemistry/instrumentation , Proteins/immunologySubject(s)
Curcumin/metabolism , DNA/metabolism , Animals , Antineoplastic Agents/adverse effects , Antineoplastic Agents/metabolism , Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Curcumin/adverse effects , Curcumin/therapeutic use , Electrophoresis, Agar Gel , Humans , Intercalating Agents/adverse effects , Intercalating Agents/metabolism , Intercalating Agents/therapeutic use , Neoplasms/drug therapy , Neoplasms/pathologyABSTRACT
C1q is of interest in systemic lupus erythematosus (SLE) research due to deficiencies in its activity being associated with the disease. Current published protocols for measuring C1q vary greatly in their results and ease of reproducibility. Due to this, average C1q concentrations have been reported between 56 and 276 microg/mL in non-SLE serum. We present an improved method for quantifying C1q concentrations, which employs a sandwich ELISA. This method has improved precision, cost efficiency, up-scaling, reproducibility, and uses significantly lesser volumes of serum sample when compared to RID and other methods for quantifying C1q. We report an average concentration of 113 +/- 40 microg/mL for C1q in non-SLE serum. The assay designed here will be useful in the high-throughput measurement of serum C1q in SLE cases.
