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      Thrombocytopenia: A Diagnostic Dilemma and Incidental Detection of Systemic Lupus Erythematosus in a Middle-Aged Asian Male

      case-report
      1 , 2 , 3 , , 4 , 5 , 3 , 2 , 6
      ,
      Cureus
      Cureus
      systemic lupus erythematosus, thrombocytopenia, male lupus, complement levels, anti-double-stranded dna

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          Abstract

          Systemic lupus erythematosus is a multisystem disorder much more common in females than males due to the effect of the hormone estrogen. There are also specific differences in clinical presentation in men and women. We present a unique case of a 54-year-old middle-aged Asian male presenting with only generalized weakness without other systemic features and with only incidental finding of thrombocytopenia. Notable laboratory values were positive for antinuclear antibody (ANA) and anti-double-stranded DNA (dsDNA), low complement 3 level with normal complement 4 levels, along with severe thrombocytopenia and mild anemia. The patient was eventually diagnosed with systemic lupus erythematosus based on these parameters. Bone marrow biopsy revealed an increased number of megakaryocytes without hypocellular or hypercellular marrow and no dysplasia of cell lines. He was initiated on oral prednisone, and his symptoms recovered remarkably with normalization of lab values upon discharge. The case's importance lies in the fact that the diagnosis of lupus can be missed in male patients with nonspecific clinical features due to certain differences in presentation from females. This diagnosis should be included in the workup of any thrombocytopenia.

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          Most cited references18

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          What does the "four core genotypes" mouse model tell us about sex differences in the brain and other tissues?

          The "four core genotypes" (FCG) model comprises mice in which sex chromosome complement (XX vs. XY) is unrelated to the animal's gonadal sex. The four genotypes are XX gonadal males or females, and XY gonadal males or females. The model allows one to measure (1) the differences in phenotypes caused by sex chromosome complement (XX vs. XY), (2) the differential effects of ovarian and testicular secretions, and (3) the interactive effects of (1) and (2). Thus, the FCG model provides new information regarding the origins of sex differences in phenotype that has not been available from studies that manipulate gonadal hormone levels in normal XY males and XX females. Studies of the FCG model have uncovered XX vs. XY differences in behaviors (aggression, parenting, habit formation, nociception, social interactions), gene expression (septal vasopressin), and susceptibility to disease (neural tube closure and autoimmune disease) not mediated by gonadal hormones. Some sex chromosome effects are mediated by sex differences in dose of X genes or their parental imprint. Future studies will identify the genes involved and their mechanisms of action.
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            Epigenetic effects of polymorphic Y chromosomes modulate chromatin components, immune response, and sexual conflict.

            Genetic conflicts between sexes and generations provide a foundation for understanding the functional evolution of sex chromosomes and sexually dimorphic phenotypes. Y chromosomes of Drosophila contain multi-megabase stretches of satellite DNA repeats and a handful of protein-coding genes that are monomorphic within species. Nevertheless, polymorphic variation in heterochromatic Y chromosomes of Drosophila result in genome-wide gene expression variation. Here we show that such naturally occurring Y-linked regulatory variation (YRV) can be detected in somatic tissues and contributes to the epigenetic balance of heterochromatin/euchromatin at three distinct loci showing position-effect variegation (PEV). Moreover, polymorphic Y chromosomes differentially affect the expression of thousands of genes in XXY female genotypes in which Y-linked protein-coding genes are not transcribed. The data show a disproportionate influence of YRV on the variable expression of genes whose protein products localize to the nucleus, have nucleic-acid binding activity, and are involved in transcription, chromosome organization, and chromatin assembly. These include key components such as HP1, Trithorax-like (GAGA factor), Su(var)3-9, Brahma, MCM2, ORC2, and inner centromere protein. Furthermore, mitochondria-related genes, immune response genes, and transposable elements are also disproportionally affected by Y chromosome polymorphism. These functional clusterings may arise as a consequence of the involvement of Y-linked heterochromatin in the origin and resolution of genetic conflicts between males and females. Taken together, our results indicate that Y chromosome heterochromatin serves as a major source of epigenetic variation in natural populations that interacts with chromatin components to modulate the expression of biologically relevant phenotypic variation.
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              A role for sex chromosome complement in the female bias in autoimmune disease

              Most autoimmune diseases are more common in women than in men. This may be caused by differences in sex hormones, sex chromosomes, or both. In this study, we determined if there was a contribution of sex chromosomes to sex differences in susceptibility to two immunologically distinct disease models, experimental autoimmune encephalomyelitis (EAE) and pristane-induced lupus. Transgenic SJL mice were created to permit a comparison between XX and XY within a common gonadal type. Mice of the XX sex chromosome complement, as compared with XY, demonstrated greater susceptibility to both EAE and lupus. This is the first evidence that the XX sex chromosome complement, as compared with XY, confers greater susceptibility to autoimmune disease.
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                Author and article information

                Journal
                Cureus
                Cureus
                2168-8184
                Cureus
                Cureus (Palo Alto (CA) )
                2168-8184
                11 September 2020
                September 2020
                : 12
                : 9
                : e10375
                Affiliations
                [1 ] General Medicine, Jagannath Gupta Institute of Medical Sciences and Hospital, Kolkata, IND
                [2 ] Nephrology, University of Virginia, Charlottesville, USA
                [3 ] Nephrology, Liberty University College of Osteopathic Medicine, Lynchburg, USA
                [4 ] Internal Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, USA
                [5 ] Rheumatology, Adventist Medical Center, Hanford, USA
                [6 ] Nephrology/Internal Medicine, Lynchburg General Hospital, Lynchburg, USA
                Author notes
                Article
                10.7759/cureus.10375
                7550011
                feed8539-707c-4a50-b481-625a1f037d69
                Copyright © 2020, Maitra et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 25 August 2020
                : 11 September 2020
                Categories
                Internal Medicine
                Rheumatology
                Hematology

                systemic lupus erythematosus,thrombocytopenia,male lupus,complement levels,anti-double-stranded dna

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