Rheumatologists are experts in treating arthritis and autoimmune diseases. Rheumatologists are specially trained to diagnose and treat inflammatory diseases of the joints and soft tissues (tendons, ligaments, muscles, and bones), and care for patients with arthritis, gout, tendonitis and a variety of other joint and connective tissue disorders.
Inflammation of the joints, muscles and other soft tissues are caused by wear and tear, infection, or disorders of the immune system, called autoimmune diseases. These latter conditions include rheumatoid arthritis, lupus, polymyositis, polymyalgia rheumatica, and many forms of vasculitis. Recent advancements in understanding the causes of arthritis led to the introduction of new medications that revolutionized the treatment of many debilitating joint diseases.
Arthritis, Rheumatic Diseases, Autoimmune Diseases, Systemic Lupus Erythematosus, Transaldolase Deficiency
Rheumatology, Immunology, Physician-Scientist Training
Genes and Viruses Predisposing to Autoimmunity, Genetics, Apoptosis, Endogenous Retroviruses, Transaldolase
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Specific areas of research in the laboratory
Molecular biology of autoantigens:
I. Expression of Human Endogenous Retroviral Sequences (ERS). ERSs and other retrotransposable elements are a major factor in shaping, reorganization, and evolution of the eukaryotic genome. The notion, that aberrant structure, expression or recognition of ERS is involved in the pathogenesis of autoimmunity, could explain both the familial aggregation and detection of cross-reactive anti-retroviral autoantibodies in patients with autoimmune diseases. HRES-1, an endogenous retroviral element that has entered the human genome at the developmental stage of old world primates, has been cloned in this laboratory. The HRES-1 genomic locus has been mapped to a common fragile site on the long arm of human chromosome 1. It is transcriptionally active, and contains two open reading frames. In contrast to most nuclear aut oantigens which are ubiquitously present in every nucleated human cell, HRES-1/p28 is expressed in a tissue-specific manner (Proc. Natl. Acad. Sci. USA, 89:1939-1943, 1992). Antibodies to HRES-1/p28 are detectable in patients with systemic lupus erythematosus and overlap syndromes (Arth. Rheum. 38:1660-1671, 1995). Future studies on HRES-1 will 1) determine the role of genetic variations of the HRES-1 gene locus in autoimmune diseases, 2) delineate the molecular basis of its tissue-specific expression 4) assess HRES-1 autoantibody levels and expression in association with disease activity.
II. Molecular Biology of Transaldolase (TAL) and an Associated Retrotransposable Element (TARE)
A novel retrotransposable element was cloned based on a limited sequence homology to the endogenous retroviral sequence, HRES-1. This repetitive element was found to constitute exons 2 and 3 of the coding sequence of a 38 k D autoantigen which corresponds to the human transaldolase (TAL-H) enzyme. Detection of a retrotransposon, TARE (transaldolase-associated retrotransposable element), in the coding sequence of a human gene demon strates the importance of these repetitive elements in evolution of the eukaryotic genome. Ongoing studies are focused on mobility of TARE and its role in transcriptional regulation of the TAL-H gene. TAL is a key enzyme in the nonoxidative phase of the pen tose phosphate pathway (PPP) which fulfills two essential functions, formation of ribose 5-phosphate for synthesis of nucleotides, RNA, and DNA and generation of NADPH for biosynthetic reactions and to maintain glutathione at a reduced state, thus, to protect sufhydryl groups and cellular integrity from oxygen radicals. Importance of PPP in general, and of TAL in particular, have been demonstrated in numerous processes involving programmed cell death (PCD), e.g. host defence mechanisms against oxidative stress, inflammation, lymphocyte activation, phagocytosis, embryogenesis, myelination, and extreme sensitivity of oligodendrocytes to PCD. The role of TAL-H in PCD is curre ntly being evaluted by gene transfection studies. Molecular biology and autoantigenicity of TAL is particularly significant in patients with multiple sclerosis (MS). MS is caused by demyelination secondary to a selective loss of oligodendrocytes by immune-mediated PCD. Molecular mimicry between viral core proteins and the TARE-encoded segment of TAL-H may play a role in breaking immunological tolerance and leading to a selective destruction of oligodendrocytes in MS.
Three-dimensional model of human transaldolase (TAL-H) displayed with the Molscript program (40 ). TAL-H forms an ß barrel, 14 helices represented by spirals) around 8 ß sheets (represented by wide flat arrows). The catalytic site with the Schiff base-forming Lys142 (K142) is on strand ß4. The first and last residues (M1, K337), K142, the polar/charged residues of peptide 24 (R239, N240, K245) and peptide 28 (K277, Q280, D283), and the starting residue (Q265) of an immunodominant loop between residues 265 and 290 are shown as landmarks. Circles show the orientation of nitrogen (blue circles), oxygen (red) and carbon atoms (gray circles) of topographically exposed and charged amino acids. From Esposito et al., M., Venkatesh, V., Otvos, L., Weng, Z., Vajda, S., Banki, K. and Perl, A. (1999) Human transaldolase and cross-reactive viral epitopes identified by autoantibodies of multiple sclerosis patients. J. Immunol. 163:4027-4032.
III. Impact of TAL on redox control of apoptosis
Apoptosis is a fundamental form of programmed cell death (PCD) which is indispensable for normal development and maintenance of homeostasis within multicellular organisms. Defects in apoptosis may underlie the etiology of n eurodegenerative diseases, cancer, autoimmune diseases, and the acquired immune deficiency syndrome (AIDS). In particular, apoptosis is blocked at various levels in cancer cells. By contrast, increas ed apoptosis underlies the etiology of T cell depletion in AIDS. Reactive oxygen intermediates (ROIs) have long been considered as toxic by-products of aerobic existence, but evidence is now accumulating that controlled levels of ROIs modulate cellular function and are necessary for signal-transduction pathways, including those mediating apoptosis. Transaldolase (TAL) is a key enzyme of the reversible nonoxidative branch of the pentose phosphate pathway (PPP) which is responsible for generation of NADPH to maintain glutathione at a reduced state (GSH) and, thus, to protect cellular integrity from ROIs. To evaluate the role of TAL in this process, Jurkat and H9 human T cells were permanently transf ected with TAL expression vectors oriented in the sense or antisense direction. Overexpression of TAL resulted in a decrease in G6PD and 6PGD activities and NADPH and GSH levels and rendered these cells highly susceptible to apoptosis induced by serum deprivation, hydrogen peroxide, nitric oxide, tumor necrosis factor (TNF), anti-Fas monoclonal antibody or infection by HIV-1. In addition, reduced levels of TAL resulted in increased G6PD and 6PGD activities and in creased GSH levels with inhibition of apoptosis in all systems. Our results provide definitive evidence that TAL has a role in regulating the balance between the two branches of PPP and its overall output as measured by GSH production and thus influences sensitivity to cell death signals. The effect of TAL expression on susceptibility to apoptosis through regulating the PPP and GSH production is consistent with an involvement of ROIs in each pathway tested. Currect efforts are directed towards TAL-mediated regulation of metabolism and specific cell death programs.
IV. Mitochonrial hyperpolarization (MHP) is an early and reversible event in T cell activation and apoptosis
Disruption of the mitochondrial transmembrane potential (MTP) has been proposed as the point of no return in apoptotic signaling. MTP is dependent upon the electron transport chain transferring electrons from NADH to molecular oxygen and proton transport mediated by the F0/F1 -ATPase complex. The energy stored in the electrochemical gradient is utilized by F0/F1 -ATPase to convert ADP to ATP during oxidative phosphorylation. We have discovered that elevation of MTP or MHP occurs in the early phase of Fas-induced apoptosis of Jurkat human leukemia T cells and normal human PBL. MHP precedes phosphatidyl serine (PS) externalization and disruption of MTP in Fas- and H2O2 -induced apoptosis. These observations were confirmed and extended to p53, TNF, and staurosporin-induced apoptosis by other laboratories. Elevation of MTP is independent from activation of caspases and represents an early event in apoptosis. With MHP and extrusion of H+ ions from the mitochondrial matrix, the cytochromes within the electron transport chain become more reduced which favors generation of ROI. ROIs can modify signaling initiated via the CD3/CD28 receptors. Moreover, T cell activation via CD3/CD28 receptors induces mitochondrial hyperpolarization and ROI production in normal PBL. Recent data from our laboratory suggest that T cell activation-induced MHP is mediated by Ca2+- and redox-dependent production of nitric oxide.
V. Activation and Cell Death Signaling in Systemic Lupus Erythematosus
We have discovered that lymphocytes from patients with SLE exhibit mitochondrial hyperpolarization, leading to abnormal activation and cell death signaling. Mitochodnrial hyperpolarization (MHP) leads increased production of reactive oxygen intermediates, cytoplasmic alkalinization, and ATP depletion which in turn predisposes to necrosis in response to activation and cell death signals. Understanding the molecular basis of MHP may lead to novel therapies in patients with SLE.
Perl, A., J.D. Rosenblatt, I.S.Y. Chen, J.P. DiVincenzo, R. Bever , B.J. Poiesz, and G.N. Abraham (1989) Detection and cloning of new HTLV-related sequences in man. Nucleic Acids Res.17, 6841-6854.
Banki, K., J.S. Maceda, E. Hurley, E. Ablonczy, D. Mattson, L. Szegedy, C. Hung and A. Perl (1992) HRES-1, a human endogenous retroviral sequence encodes a 28 kd protein: a possible autoantigen for HTLV gag-reactive autoantibodies. Proc. Natl. Acad. Sci. USA, 89, 1939-1943.
Krieg, A.M., Gourley, M.F. and Perl, A. (1992) Endogenous retroviruses: Potential etiologic: agents in autoimmunity. FASEB J. 6:2537-2544.
Perl, A. and Banki, K. (1993) Human endogenous retroviral elements and autoimmunity: data and concepts. Trends Microbiol. 1:153-156.
Banki, K., Halladay, D. and Perl, A. (1994) Cloning and Expression of the Human Gene for Transaldolase: a Novel Highly Repetitive Element Constitutes an Integral Part of the Coding Sequence. J. Biol. Chem. 269:2847-2851.
Banki, K., E. Colombo, F. Sia, D. Halladay, D. H. Mattson, A.H. Tatum, P. T. Massa, P. E. Phillips, Perl, A. (1994) Oligodendrocyte-specific expression and autoantigenicity of transaldolase in multiple sclerosis. J. Exp. Med. 180:1649-1663.
Perl, A., Colombo, E., Dai, H., Agarwal, R.K., Mark, K., Banki, K., Poiesz, B.J., Phillips, P.E., Hoch, S.O., Reveille, J.D. and Arnett, F.C. (1995). Antibody reactivity to the HRES-1 endogenous retroviral element identifies a subset of patients with systemic lupus erythematosus and overlap syndromes: Correlation with antinuclear antibodies and HLA class II alleles. Arth. Rheum. 38: 1660-1671.
Banki, K., Hutter, E., Colombo, E., Gonchoroff, N.J. and Perl, A. (1996) Glutathione levels and sensitivity to apoptosis are regulated by changes in transaldolase expression. J. Biol. Chem.. 271: 32994-33001.
Banki, K., Eddy, R.L., Shows, T.B., Halladay, D.L., Bullrich, F., Croce, C.M., Jurecic, V., Baldini, A. and Perl, A. (1997) The human transaldolase gene is located on chromosome 11 at p15.4 -p15.5. Genomics, 45: 233-238.
Colombo, E., Banki, K., Tatum, A.H., Daucher, J., Ferrante, P., Murray, R.S., Phillips, P.E. and Perl, A. (1997) Comparative analysis of antibody and cell-mediated autoimmunity to transaldolase and myelin basic protein in patients with multiple sclerosis. J. Clin. Invest. 99:1238-1250.
Banki, K., Hutter, E., Gonchoroff, N.J. and Perl, A. (1998) Molecular ordering in HIV-induced apoptosis: oxidative stress, activation of caspases and cell survival are regulated by transaldolase. J. Biol. Chem. 273:11944-11953.
Banki, K., Hutter, E., Gonchoroff, N.J. and Perl, A.(1999) Elevation of mitochondrial transmembrane potential and ROI levels are early even ts and independent from activation of caspases in Fas signaling. J. Immunol. 162:1466-1479.
Magistrelli, C., Samoilova, E., Agarwal, R.K., Banki, K., Ferrante, P., Vladutiu, A., Phillips, P.E. and Perl, A. (1999) Polymorphic genotypes of the HRES-1 human endogenous retrovirus locus are associated with systemic lupus erythematosus and autoreactivity. Immunogenetics, 49:829-834.
Esposito, M., Venkatesh, V., Otvos, L., Weng, Z., Vajda, S., Banki, K. and Perl, A. (1999) Human transaldolase and cross-reactive viral epitopes identified by autoantibodies of multiple sclerosis patients. J. Immunol. 163:4027-4032.
Perl, A. (1999) Mechanisms of viral pathogenesis in rheumatic diseases. Ann. Rheum. Dis. 58:454-461.
Perl, A., Colombo, E., Samoilova, E., Butler, M.C. and Banki. K. (2000) Human transaldolase-associated repetitive elements are transcribed by RNA polymerase III. J. Biol. Chem. 275:7261-7272.
Puskas, F., Gergely, P. Jr., Banki, K. and Perl. A (2000) Stimulation of the pentose phosphate pathway and glutathione levels by dehydroascorbate, the oxidized form of vitamin C. FASEB J. 14:1352-1361.
Perl, A. and Banki, K. (2000) Genetic and Metabolic Control of the Mitochondrial Transmembrane Potential and Reactive Oxygen Intermediate Production in HIV disease. Antioxid. Redox Signal. 2:551-573.
Perl, A. (2001) Endogenous Retroviruses in the Pathogenesis of Autoimmunity. Editorial. J. Rheumatol. 28:461-464.
Lachaise, F., Martin, G., Drougard, C., Perl, A, Vuillaume, M., Wegnez, M., Sarasin, A., Daya-Grosjean, L. (2001) Relationship between post-translational modification of transaldolase and catalase deficiency in UV-sensitive repair-deficient Xeroderma pigmentosum fibroblasts and SV40-transformed human cells. Free Rad. Biol. Med. 30:1365-1373.
Perl, A. (2001) Abnormal Apoptosis in Systemic Lupus. Lupus News, 21:16-17.
Gergely, P. Jr., Grossman, C. , Niland, B. , Puskas, F. , Neupane, H. , Allam, F. , Banki, K. , Phillips, P.E. and Perl, A. (2002) Mitochondrial hyperpolarization and ATP depletion in patients with systemic lupus erythematosus. Arth. Rheum. 46:175-190.
Puskas, F., Gergely, P., Niland, B., Banki, K. and Perl, A. (2002) Differential regulation of hydrogen peroxide and Fas-dependent apoptosis pathways by dehydroascorbate, the oxidized form of vitamin C. Antiox. Redox Signal. 4:357-369.
Perl, A, Gergely, P., Puskas, F. and Banki, K. (2002) Metabolic switches of T cell activation and apoptosis. Antiox. Redox Signal. 4:427-443.
Gergely, P. Jr., Niland, B., Gonchoroff, N., Pullmann, R. Jr., Phillips, P.E. and Perl, A. (2002) Persistent mitochondrial hyperpolarization, increased reactive oxygen intermediate production, and cytoplasm ic alkalinization characterize altered IL-10 signaling in patients with systemic lupus erythematosus. J. Immunol. 169:1092-1101.
Nagy, Gy, Koncz, A. and Perl A (2003) T cell activation-induced mitochondrial hyperpolarization is mediated by Ca2+- and redox-dependent production of nitric oxide. J. Immunol. 171: 5188-5197.
Grossman, C.E., Qian, Y., Banki, K. and Perl, A. (2004) ZNF143 mediates basal and tissue-specific expression of human transaldolase. J. Biol. Chem. 279: 12190-12205.
Perl,A.; Gergely,P.,Jr.; Banki,K. (2004) Mitochondrial dysfunction in T cells of patients with systemic lupus erythematosus. Int. Rev. Immunol. 23:293-313.
Grossman, C. E., Niland, B., Stancato, C, Verhoeven, N.M., van der Knaap, M.S., Jakobs, C., Brown, L.M., Vajda, S., Banki, K. and Perl, A. (2004) Deletion of serine 171 causes inactivation, proteasome-mediated degradation and complete deficiency of human transaldolase. Biochem. J. 382:725-231.
Nagy, Gy, Barcza. M., Gonchoroff, N., Phillips, P.E. and Perl, A. (2004) Nitric oxide-dependent mitochondrial biogenesis generates Ca2+ signaling profile of lupus T cells. J. Immunol. 173:3676-3683.
Nagy, Gy, Koncz, A, Phillips, P.E. and Perl, A. (2005) Mitochondrial signal transduction abnormalities in systemic lupus erythematosus. Curr. Immunol. Rev. 1: 61-67.
Gergely. P. Jr,Pullmann, R., Stancato, C., Otvos, L. Jr, Koncz, A., Blazsek, A., Poor, Gy,Brown, K.E., Phillips, P.E. and Andras Perl. (2005) Increased prevalence of transfusion-transmitted virus and cross-reactivity with immunodominant epitopes of the HRES-1/p28 endogenous retroviral autoantigen in patients with systemic lupus erythematosus. Clin. Immunol. 116: 124-134.
Nagy, Gy, Koncz, A, and Perl, A. (2005) T- and B-cell abnormalities in systemic lupus erythematosus. Crit. Rev. Immunol. 25: 123-140.
Nagy, Gy, Koncz, A, and Perl, A. (2005) Signal transduction abnormalities in systemic lupus erythematosus (In Hungarian). Orv. Hetil. 146:1625-1630.
Niland, B., Banki, K., Biddison, W.E.and Perl, A. (2005)CD8+ T cell-mediated HLA-A*0201-restricted cytotoxicity to transaldolase peptide 168-176 in patients with multiple sclerosis. J. Immunol. 175: 8365-8378.
Nagy G.and Perl, A. (2006) The role of nitric oxide in abnormal T cell signal transduction in systemic lupus erythematosus. Clin. Immunol. 118: 145-151.
Vas, Gy., Conkrite, K., Amidon, W., Qian, Y., Banki, K., and Perl, A. (2006) Study of transaldolase deficiency in urine samples by LC-MS/MS. J. Mass. Spec. 41: 463-469.
Fernandez, D., Bonilla, E., Mirza, N, Niland, B. and Perl, A. (2006) Rapamycin reduces disease activity and normalizes T-cell activation-induced calcium fluxing in patients with systemic lupus erythematosus. Arth. Rheum. 54: 2983-2988.
Perl, A., Qian, Y, Chohan, K.R., Shirley, C.R., Amidon, W., Banerjee, S., Middleton, F.A., Conkrite, K.L., Barcza, M., Gonchoroff, N., Suarez, S.S., and Banki, K. (2006) Transaldolase is essential for maintenance of the mitochondrial transmembrane potential and fertility of spermatozoa.Proc. Natl. Acad. Sci. USA, 103: 14813-14818.
Nagy, G., Ward, J., Mosser, D.D., Koncz, A., Gergely, P.Jr., Stancato, S., Qian, Y, Fernandez, D., Niland, B., Grossman, C.E., Telarico, T, Banki, K, Perl, A. (2006) Regulation of CD4 expression via recycling by HRES‑1/RAB4 controls susceptibility to HIV infection. J. Biol. Chem. 281: 34574-34591
Fernandez, D., Bonilla, Phillips, P.E. and Perl, A. (2006)Signaling abnormalities in systemic lupus erythematosus as potential drug targets. Endocrin, Metabolic & Immune Disorders - Drug Targets. 6: 305-311.
Gergely, P., Perl, A. and Poor, Gy. (2006) Possible pathogenic nature of the recently discovered TT virus. Does it play a role in autoimmune rheumatic diseases? Autoimmun. Rev. 6:5-9.
LaRocca, D., Lehmann, D.F., Perl, A., Ozawa, T., Holohan, P. D. (2006) The combination of nuclear and mitochondrial mutations as a risk factor for idiosyncratic toxicity. Brit. J. Clin. Pharm. 63:249-251.
Silberstein, M., Landon, M.R., Wang, Y.E., Perl, A. and Vajda, S. (2006) Computational methods for functional site identification suggest a substrate access channel in transaldolase. Genome Inform. 17: 13-22.
Koros, A., Hanczko,R., Jambor, Qian, Y., Perl, A. and Molnar-Perl, I. (2007) Analysis of amino acids and biogenic amines in biological tissues as their o-phthalaldehyde/ethanethiol/fluorenylmethyl chloroformate derivatives by high-performance liquid chromatography: A deproteinization study. J. Chromatogr. A 1149: 46-55.
Nagy, G., Koncz, A., Fernandez, D. and Perl A. (2007). Nitric oxide, mitochondrial hyperpolarization, and T-cell activation. Free Radic. Biol. Med. 42: 1625-1631.
Perl, A. (2007) The pathogenesis of transaldolase deficiency. IUBMB Life 59: 365-373.
Bonilla, E., Francis, L., Allam, F., Ogrinc, M., Neupane, H., Phillips, P.E., and Perl, A. (2007) Immunofluorescence microscopy is superior to fluorescent beads for detection of antinuclear antibody reactivity in systemic lupus erythematosus patients. Clin. Immunol. 124:18-21.
Hanczko, R., Jambor, A., Perl, A., and I Molnar-Perl (2007) Advances in the o-phthalaldehyde derivatizations:Comeback to the o-phthalaldehyde-ethanethiol reagent. J. Chromatogr. A 1163: 25-42.
Pullmann, R. Jr., Bonilla, E., Phillips, P.E., Middleton, F.A. and Perl, A. (2008) Haplotypes of the HRES-1 endogenous retrovirus are associated with development and disease manifestations of systemic lupus erythematosus. Arth. Rheum. 58: 532-540.
Francis L, Bonilla E, Soforo E, Neupane H, Nakhla H, Fuller C, and Perl A. (2008) Fatal toxic myopathy attributed to propofol, methylprednisolone, and cyclosporine after prior exposure to colchicine and simvastatin. Clin. Rheumatol. 27:129-31.
Perl, A., Nagy, G., Koncz, A., Gergely, P., Fernandez, D., Doherty, E., Telarico, T., Bonilla, E. and Phillips, P.E. (2008) Molecular mimicry and immunomodulation by the HRES-1 endogenous retrovirus in SLE. Autoimmunity, 41:287-297.
Qian, Y., Banerjee, S., Grossman, C.E., Amidon, A., Nagy, Gy., Barcza, M., Niland, B., Karp, D.R., Banki, K., and Perl, A. (2008) Transaldolase deficiency influences the pentose phosphate pathway, mitochondrial homeostasis, and apoptosis signal processing. Biochem. J. 415:123-134.
Vyshkina, T., Sylvester, A., Sadiq, S., Bonilla, E., Canter, J., Perl, A. and Kalman, B.(2008) Association of Common Mitochondrial DNA Variants with Multiple Sclerosis and Systemic Lupus Erythematosus. Clin. Immunol. 129:31-35.
Vyshkina, T., Sylvester, A., Sadiq, S., Bonilla, E., Perl, A. and Kalman, B.(2008) CCL genes in multiple sclerosis and systemic lupus erythematosus. J. Neuroimmunol. 200:145-152.
Perl, A. (2009) Overview of Signal Processing by the Immune System in SLE. Autoimmun. Rev. 8:177-178.
Fernandez D.R. and Perl, A. (2009) Metabolic control of T-cell activation and death in SLE. Autoimmun. Rev. 8:184-189.
Fernandez, D.R. Telarico, T., Bonilla, E., Li, Q., Banerjee, S., Middleton, F.A., Phillips, P.E., Crow, M.K., Oess, S., Muller-Esterl, W., and Perl, A. (2009) Activation of mTOR controls the loss of TCRζ in lupus T cells through HRES-1/Rab4-regulated lysosomal degradation. J. Immunol. 182: 2063-2073.
Hanczko, R., Fernandez, D.R., Doherty, E., Qian, Y., Vas, G., Niland, B., Telarico, T., Garba, A., Banerjee, S., Middleton, F.A., Barrett, D., Barcza, M., Banki, K., Landas, S.K. and Perl, A. (2009) Prevention of hepatocarcinogenesis and increased susceptibility to acetaminophen-induced liver failure in transaldolase-deficient mice by N-acetylcysteine. J. Clin. Invest. 119:1546-1557.
Francis, L. and Perl. A. (2009) Pharmacotherapy of SLE. Expert. Opin. Pharmacother. 10: 1481-1494.
Perl, A., Fernandez, D., Telarico, T., Francis, L. and Phillips, P.E. (2009) T- and B-cell signaling biomarkers and treatment targets in lupus. Curr. Opin. Rheumatol. 21: 454-464.
Perl, A. (2009) Editorial: Emerging New Pathways of Pathogenesis and Targets for Treatment in Systemic Lupus Erythematosus and Sjogren's Syndrome. Curr. Opin. Rheumatol. 21: 443-447.
Bedoya, F., Medveczky, M.M., Lund, T.C., Perl, A., Horvath, J., Jett, S.D. and Medveczky, P.G. (2009) Identification of Mitochondrial Genome Concatamers in AIDS-associated lymphomas and lymphoid cell lines. Leuk. Res. 33:1499-1504.
Tily, HI and Perl, A. (2009) Lymphedema: a paradoxical effect of tumor necrosis factor inhibitors - case report and review of literature. BMJ Case Reports [doi:10.1136/bcr.07.2008.0520]
Blank, M., Shoenfeld, Y. and Perl, A. (2009) Cross-talk of the environment with the host genome and the immune system through endogenous retroviruses in systemic lupus erythematosus. Lupus, 18: 1136-1143.
Soforo, E., Baumgartner, M., Francis, L., Allam, F., Phillips, P.E., and Perl, A. (2010) Induction of systemic lupus erythematosus with TNF blockers. J. Rheumatol. 37:204-205.
Francis, L. and Perl. A. (2010) Infection in systemic lupus erythematosus: friend or foe? Int. J. Clin. Rheumatol. 5:59-74.
Perl, A. (2010) Editorial: Pathogenic Mechanisms in Systemic Lupus Erythematosus. Autoimmunity, 43:1-6.
Perl, A. (2010) Systems biology of lupus: mapping the impact of genomic and environmental factors on gene expression signatures, cellular signaling, metabolic pathways, hormonal and cytokine imbalance and selecting targets for treatment. Autoimmunity 43: 32-47.
Tily, H., Banki, K., Hoffman, G.S. and Perl. A. (2010) Detection of lupus anti-coagulant and successful anti-coagulation in familial Sneddon syndrome. Ann. Rheum. Dis. 69: 775-776.
Niland, B, Miklossy, G, Banki, K, Biddison, W.E., Casciola-Rosen, L., Rosen, A., Martinvalet, D., Lieberman, J., and Perl, A. (2010) Cleavage of transaldolase by granzyme B causes the loss of enzymatic activity with retention of antigenicity for multiple sclerosis patients. J. Immunol., 184:4025-32.