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Differential expression of BAFF and its receptors in discoid lupus erythematosus patients
Institution:1. University of Texas Southwestern Medical Center, Department of Dermatology, Dallas, TX, USA;2. ProPath, Dallas, TX, USA;1. Department of Dermatology, The Jikei University School of Medicine, Japan;2. Laboratory for Respiratory Diseases, Center for Genomic Medicine, RIKEN, Japan;3. Department of Dermatology, Tokyo Women''s Medical University, Japan;4. Department of Dermatology, Faculty of Medicine, University of Tokyo, Japan;5. Department of Dermatology, Teikyo University School of Medicine, Japan;6. Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Japan;7. Miyatake Asthma Clinic, Japan;8. Takao Hospital, Japan;9. Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan;10. Department of Dermatology, Keio University School of Medicine, Japan;11. Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Japan;1. Medicine, Division of Rheumatology, NYU Langone Health, 301 East 17th St, Suite 1410, New York, NY 10003;2. Pathology, NYU Langone Health, New York, NY;1. Drexel University College of Medicine, Philadelphia, Pennsylvania;2. Harvard Medical School and Clinical Laboratory for Epidemiology and Applied Research in Skin (CLEARS), Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts;3. Harvard Medical School, Brigham and Women''s Hospital Dermatology, Boston, Massachusetts;1. Department of Medical Oncology, City of Hope, Duarte, CA;2. Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO;3. Division of Medical Oncology, University of Washington, Seattle Cancer Care Alliance, Seattle, WA;4. Guardant Health, Redwood City, CA;1. Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan;2. Research Institute, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan;3. Graduate School of Informatics, Kyoto University, Kyoto, Japan
Abstract:BackgroundB-cell activating factor of the TNF family (BAFF) promotes the maturation and survival of B cells. Because BAFF levels are elevated in systemic lupus erythematosus (SLE) patients, BAFF has been the target of emerging therapies for SLE, such as belimumab. Levels of BAFF and its receptors in discoid lupus erythematosus (DLE) patients are unknown.ObjectiveTo compare skin and blood mRNA and protein levels of BAFF and its receptors BAFF-R, TACI, and BCMA in DLE subjects with (DLE+/SLE+ (N = 28)) and without SLE (DLE+/SLE− (N = 35)), psoriasis subjects (N = 11), and normal subjects (N = 42).MethodsWe used quantitative real-time PCR to measure blood and skin BAFF, BAFF-R, TACI, and BCMA mRNA, sandwich ELISAs to measure sera BAFF, and immunohistochemistry to evaluate BAFF and BAFF-R skin protein expression.ResultsBAFF mRNA and protein levels were highest in DLE+/SLE+blood, followed by DLE+/SLE−, psoriasis, and normal blood. BAFF protein also correlated with anti-nuclear antibodies, and autoantibodies against double-stranded DNA, single-stranded DNA, and ribonucleoprotein, and Systemic Lupus Erythematosus Disease Activity Index scores in DLE patients. While showing no difference between DLE+/SLE+ and DLE+/SLE− skin, BAFF and its receptors mRNA were up-regulated in DLE skin vs. normal and psoriasis skin. DLE skin had higher percentages of BAFF-R+ inflammatory cells, likely T cells and macrophages, than psoriasis and normal skin.ConclusionsBAFF may be a serologic marker of systemic disease in DLE patients. BAFF and its receptors are elevated in DLE skin, suggesting that targeted therapies against these proteins could treat refractory DLE patients.
Keywords:Discoid lupus erythematosus  Systemic lupus erythematosus  BAFF  BAFF-R  T cell  Macrophage
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