Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Immunologic Research
Published in: Immunologic Research 1-3/2015

01-12-2015 | AUTOIMMUNITY/IMMUNOREGULATION/INFLAMMATION

Lupus brain fog: a biologic perspective on cognitive impairment, depression, and fatigue in systemic lupus erythematosus

Author: Meggan Mackay

Published in: Immunologic Research | Issue 1-3/2015

Login to get access

Abstract

Cognitive disturbances, mood disorders and fatigue are common in SLE patients with substantial adverse effects on function and quality of life. Attribution of these clinical findings to immune-mediated disturbances associated with SLE remains difficult and has compromised research efforts in these areas. Improved understanding of the role of the immune system in neurologic processes essential for cognition including synaptic plasticity, long term potentiation and adult neurogenesis suggests multiple potential mechanisms for altered central nervous system function associated with a chronic inflammatory illness such as SLE. This review will focus on the biology of cognition and neuroinflammation in normal circumstances and potential biologic mechanisms for cognitive impairment, depression and fatigue attributable to SLE.
Literature
1.
Bortoluzzi A, et al. Development and validation of a new algorithm for attribution of neuropsychiatric events in systemic lupus erythematosus. Rheumatology (Oxford). 2015;54(5):891–8.CrossRef
2.
Hanly JG, et al. Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: an international inception cohort study. Arthritis Rheum. 2007;56(1):265–73.PubMedCrossRef
3.
Peretti CS, et al. Cognitive impairment in systemic lupus erythematosus women with elevated autoantibodies and normal single photon emission computerized tomography. Psychother Psychosom. 2012;81(5):276–85.PubMedCrossRef
4.
Kozora E, et al. Immune function and brain abnormalities in patients with systemic lupus erythematosus without overt neuropsychiatric manifestations. Lupus. 2012;21(4):402–11.PubMedCrossRef
5.
Nowicka-Sauer K, et al. Neuropsychological assessment in systemic lupus erythematosus patients: clinical usefulness of first-choice diagnostic tests in detecting cognitive impairment and preliminary diagnosis of neuropsychiatric lupus. Clin Exp Rheumatol. 2011;29(2):299–306.PubMed
6.
Petri M, et al. Depression and cognitive impairment in newly diagnosed systemic lupus erythematosus. J Rheumatol. 2010;37(10):2032–8.PubMedCrossRef
7.
Ainiala H, et al. The prevalence of neuropsychiatric syndromes in systemic lupus erythematosus. Neurology. 2001;57(3):496–500.PubMedCrossRef
8.
Krupp LB, et al. A study of fatigue in systemic lupus erythematosus. J Rheumatol. 1990;17(11):1450–2.PubMed
9.
Palagini L, et al. Depression and systemic lupus erythematosus: a systematic review. Lupus. 2013;22(5):409–16.PubMedCrossRef
10.
Schmeding A, Schneider M. Fatigue, health-related quality of life and other patient-reported outcomes in systemic lupus erythematosus. Best Pract Res Clin Rheumatol. 2013;27(3):363–75.PubMedCrossRef
11.
Crowther AJ, Song J. Activity-dependent signaling mechanisms regulating adult hippocampal neural stem cells and their progeny. Neurosci Bull. 2014;30(4):542–56.PubMedCentralPubMedCrossRef
12.
13.
Yirmiya R, Goshen I. Immune modulation of learning, memory, neural plasticity and neurogenesis. Brain Behav Immun. 2011;25(2):181–213.PubMedCrossRef
14.
15.
16.
Shors TJ, Matzel LD. Long-term potentiation: what’s learning got to do with it? Behav Brain Sci. 1997;20(4):597–614.PubMed
17.
Kipnis J, et al. Dual effect of CD4+ CD25+ regulatory T cells in neurodegeneration: a dialogue with microglia. Proc Natl Acad Sci USA. 2004;101(Suppl 2):14663–9.PubMedCentralPubMedCrossRef
18.
Ron-Harel N, et al. Age-dependent spatial memory loss can be partially restored by immune activation. Rejuvenation Res. 2008;11(5):903–13.PubMedCrossRef
19.
Baruch K, Schwartz M. CNS-specific T cells shape brain function via the choroid plexus. Brain Behav Immun. 2013;34:11–6.PubMedCrossRef
20.
21.
Wolf SA, et al. CD4-positive T lymphocytes provide a neuroimmunological link in the control of adult hippocampal neurogenesis. J Immunol. 2009;182(7):3979–84.PubMedCrossRef
22.
Lewitus GM, Cohen H, Schwartz M. Reducing post-traumatic anxiety by immunization. Brain Behav Immun. 2008;22(7):1108–14.PubMedCrossRef
23.
Lewitus GM, et al. Vaccination as a novel approach for treating depressive behavior. Biol Psychiatry. 2009;65(4):283–8.PubMedCrossRef
24.
Hauben E, et al. Vaccination with a Nogo-A-derived peptide after incomplete spinal-cord injury promotes recovery via a T-cell-mediated neuroprotective response: comparison with other myelin antigens. Proc Natl Acad Sci USA. 2001;98(26):15173–8.PubMedCentralPubMedCrossRef
25.
Schwartz M, Baruch K. Breaking peripheral immune tolerance to CNS antigens in neurodegenerative diseases: boosting autoimmunity to fight-off chronic neuroinflammation. J Autoimmun. 2014;54:8–14.PubMedCrossRef
26.
Ma X, Foster J, Sakic B. Distribution and prevalence of leukocyte phenotypes in brains of lupus-prone mice. J Neuroimmunol. 2006;179(1–2):26–36.PubMedCrossRef
27.
Marques F, Sousa JC. The choroid plexus is modulated by various peripheral stimuli: implications to diseases of the central nervous system. Front Cell Neurosci. 2015;9:136.PubMedCentralPubMedCrossRef
28.
29.
Szmydynger-Chodobska J, et al. Posttraumatic invasion of monocytes across the blood-cerebrospinal fluid barrier. J Cereb Blood Flow Metab. 2012;32(1):93–104.PubMedCentralPubMedCrossRef
30.
Schobitz B, De Kloet ER, Holsboer F. Gene expression and function of interleukin 1, interleukin 6 and tumor necrosis factor in the brain. Prog Neurobiol. 1994;44(4):397–432.PubMedCrossRef
31.
Vitkovic L, et al. Cytokine signals propagate through the brain. Mol Psychiatry. 2000;5(6):604–15.PubMedCrossRef
32.
Marsland AL, et al. Brain morphology links systemic inflammation to cognitive function in midlife adults. Brain Behav Immun. 2015;48:195–204.PubMedCrossRef
33.
Bucks RS, et al. Selective effects of upper respiratory tract infection on cognition, mood and emotion processing: a prospective study. Brain Behav Immun. 2008;22(3):399–407.PubMedCrossRef
34.
Krabbe KS, et al. Low-dose endotoxemia and human neuropsychological functions. Brain Behav Immun. 2005;19(5):453–60.PubMedCrossRef
35.
Reichenberg A, et al. Cytokine-associated emotional and cognitive disturbances in humans. Arch Gen Psychiatry. 2001;58(5):445–52.PubMedCrossRef
36.
Gibertini M. IL1 beta impairs relational but not procedural rodent learning in a water maze task. Adv Exp Med Biol. 1996;402:207–17.PubMedCrossRef
37.
Banks WA, Erickson MA. The blood-brain barrier and immune function and dysfunction. Neurobiol Dis. 2010;37(1):26–32.PubMedCrossRef
38.
39.
Ek M, et al. Inflammatory response: pathway across the blood-brain barrier. Nature. 2001;410(6827):430–1.PubMedCrossRef
40.
Hosoi T, Okuma Y, Nomura Y. Electrical stimulation of afferent vagus nerve induces IL-1beta expression in the brain and activates HPA axis. Am J Physiol Regul Integr Comp Physiol. 2000;279(1):R141–7.PubMed
41.
Perry VH. Stress primes microglia to the presence of systemic inflammation: implications for environmental influences on the brain. Brain Behav Immun. 2007;21(1):45–6.PubMedCrossRef
42.
Chen J, et al. Neuroinflammation and disruption in working memory in aged mice after acute stimulation of the peripheral innate immune system. Brain Behav Immun. 2008;22(3):301–11.PubMedCentralPubMedCrossRef
43.
Marsland AL, et al. Interleukin-6 covaries inversely with cognitive performance among middle-aged community volunteers. Psychosom Med. 2006;68(6):895–903.PubMedCrossRef
44.
Harrison NA, et al. Peripheral inflammation acutely impairs human spatial memory via actions on medial temporal lobe glucose metabolism. Biol Psychiatry. 2014;76(7):585–93.PubMedCentralPubMedCrossRef
45.
Davis LS, Hutcheson J, Mohan C. The role of cytokines in the pathogenesis and treatment of systemic lupus erythematosus. J Interferon Cytokine Res. 2011;31(10):781–9.PubMedCentralPubMedCrossRef
46.
Azevedo PC, Murphy G, Isenberg DA. Pathology of systemic lupus erythematosus: the challenges ahead. Methods Mol Biol. 2014;1134:1–16.PubMedCrossRef
47.
Kozora E, et al. Inflammatory and hormonal measures predict neuropsychological functioning in systemic lupus erythematosus and rheumatoid arthritis patients. J Int Neuropsychol Soc. 2001;7(6):745–54.PubMedCrossRef
48.
Shucard JL, et al. C-reactive protein and cognitive deficits in systemic lupus erythematosus. Cogn Behav Neurol. 2007;20(1):31–7.PubMedCrossRef
49.
Chiche L, et al. Modular transcriptional repertoire analyses of adults with systemic lupus erythematosus reveal distinct type I and type II interferon signatures. Arthritis Rheumatol. 2014;66(6):1583–95.PubMedCentralPubMedCrossRef
50.
Crow MK. Interferon pathway activation in systemic lupus erythematosus. Curr Rheumatol Rep. 2005;7(6):463–8.PubMedCrossRef
51.
52.
53.
Capuron L, Miller AH. Cytokines and psychopathology: lessons from interferon-alpha. Biol Psychiatry. 2004;56(11):819–24.PubMedCrossRef
54.
Nashan D, et al. Understanding and managing interferon-alpha-related fatigue in patients with melanoma. Melanoma Res. 2012;22(6):415–23.PubMedCrossRef
55.
Wichers MC, et al. Interferon-alpha-induced depressive symptoms are related to changes in the cytokine network but not to cortisol. J Psychosom Res. 2007;62(2):207–14.PubMedCrossRef
56.
Kamata M, et al. Effect of single intracerebroventricular injection of alpha-interferon on monoamine concentrations in the rat brain. Eur Neuropsychopharmacol. 2000;10(2):129–32.PubMedCrossRef
57.
Kitagami T, et al. Mechanism of systemically injected interferon-alpha impeding monoamine biosynthesis in rats: role of nitric oxide as a signal crossing the blood-brain barrier. Brain Res. 2003;978(1–2):104–14.PubMedCrossRef
58.
Raison CL, et al. Activation of central nervous system inflammatory pathways by interferon-alpha: relationship to monoamines and depression. Biol Psychiatry. 2009;65(4):296–303.PubMedCentralPubMedCrossRef
59.
Lichtblau N, et al. Cytokines as biomarkers in depressive disorder: current standing and prospects. Int Rev Psychiatry. 2013;25(5):592–603.PubMedCrossRef
60.
Schlaak JF, et al. Selective hyper-responsiveness of the interferon system in major depressive disorders and depression induced by interferon therapy. PLoS ONE. 2012;7(6):e38668.PubMedCentralPubMedCrossRef
61.
Juengling FD, et al. Prefrontal cortical hypometabolism during low-dose interferon alpha treatment. Psychopharmacology. 2000;152(4):383–9.PubMedCrossRef
62.
Capuron L, et al. Basal ganglia hypermetabolism and symptoms of fatigue during interferon-alpha therapy. Neuropsychopharmacology. 2007;32(11):2384–92.PubMedCrossRef
63.
Bachen EA, Chesney MA, Criswell LA. Prevalence of mood and anxiety disorders in women with systemic lupus erythematosus. Arthritis Rheum. 2009;61(6):822–9.PubMedCentralPubMedCrossRef
64.
Nery FG, et al. Prevalence of depressive and anxiety disorders in systemic lupus erythematosus and their association with anti-ribosomal P antibodies. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(3):695–700.PubMedCrossRef
65.
Utset TO, et al. Depressive symptoms in patients with systemic lupus erythematosus: association with central nervous system lupus and Sjogren’s syndrome. J Rheumatol. 1994;21(11):2039–45.PubMed
66.
Santer DM, et al. Potent induction of IFN-alpha and chemokines by autoantibodies in the cerebrospinal fluid of patients with neuropsychiatric lupus. J Immunol. 2009;182(2):1192–201.PubMedCentralPubMedCrossRef
67.
Winfield JB, et al. Intrathecal IgG synthesis and blood-brain barrier impairment in patients with systemic lupus erythematosus and central nervous system dysfunction. Am J Med. 1983;74(5):837–44.PubMedCrossRef
68.
69.
Lee SW, et al. The efficacy of brain (18)F-fluorodeoxyglucose positron emission tomography in neuropsychiatric lupus patients with normal brain magnetic resonance imaging findings. Lupus. 2012;21(14):1531–7.PubMedCrossRef
70.
71.
Morris G, Maes M. Oxidative and nitrosative stress and immune-inflammatory pathways in patients with myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). Curr Neuropharmacol. 2014;12(2):168–85.PubMedCentralPubMedCrossRef
72.
Lucas K, Maes M. Role of the Toll Like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway. Mol Neurobiol. 2013;48(1):190–204.PubMedCrossRef
73.
74.
75.
Morris G, Maes M. Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics. BMC Med. 2013;11:205.PubMedCentralPubMedCrossRef
76.
77.
Arriens C, et al. Placebo-controlled randomized clinical trial of fish oil’s impact on fatigue, quality of life, and disease activity in systemic lupus erythematosus. Nutr J. 2015;14(1):82.PubMedCentralPubMedCrossRef
78.
Ben Menachem-Zidon O, et al. Astrocytes support hippocampal-dependent memory and long-term potentiation via interleukin-1 signaling. Brain Behav Immun. 2011;25(5):1008–16.PubMedCrossRef
79.
Wolf G, et al. Interleukin-1 signaling is required for induction and maintenance of postoperative incisional pain: genetic and pharmacological studies in mice. Brain Behav Immun. 2008;22(7):1072–7.PubMedCrossRef
80.
Yang YM, et al. Microglial TNF-alpha-dependent elevation of MHC class I expression on brain endothelium induced by amyloid-beta promotes T cell transendothelial migration. Neurochem Res. 2013;38(11):2295–304.PubMedCrossRef
81.
82.
Goshen I, et al. A dual role for interleukin-1 in hippocampal-dependent memory processes. Psychoneuroendocrinology. 2007;32(8–10):1106–15.PubMedCrossRef
83.
Labrousse VF, et al. Impaired interleukin-1beta and c-Fos expression in the hippocampus is associated with a spatial memory deficit in P2X(7) receptor-deficient mice. PLoS ONE. 2009;4(6):e6006.PubMedCentralPubMedCrossRef
84.
Yirmiya R, Winocur G, Goshen I. Brain interleukin-1 is involved in spatial memory and passive avoidance conditioning. Neurobiol Learn Mem. 2002;78(2):379–89.PubMedCrossRef
85.
86.
Avital A, et al. Impaired interleukin-1 signaling is associated with deficits in hippocampal memory processes and neural plasticity. Hippocampus. 2003;13(7):826–34.PubMedCrossRef
87.
Goshen I, et al. Brain interleukin-1 mediates chronic stress-induced depression in mice via adrenocortical activation and hippocampal neurogenesis suppression. Mol Psychiatry. 2008;13(7):717–28.PubMedCrossRef
88.
Beattie EC, et al. Control of synaptic strength by glial TNFalpha. Science. 2002;295(5563):2282–5.PubMedCrossRef
89.
Steinmetz CC, Turrigiano GG. Tumor necrosis factor-alpha signaling maintains the ability of cortical synapses to express synaptic scaling. J Neurosci. 2010;30(44):14685–90.PubMedCentralPubMedCrossRef
90.
Stellwagen D, Malenka RC. Synaptic scaling mediated by glial TNF-alpha. Nature. 2006;440(7087):1054–9.PubMedCrossRef
91.
Balschun D, et al. Interleukin-6: a cytokine to forget. Faseb J. 2004;18(14):1788–90.PubMed
92.
Jankowsky JL, Derrick BE, Patterson PH. Cytokine responses to LTP induction in the rat hippocampus: a comparison of in vitro and in vivo techniques. Learn Mem. 2000;7(6):400–12.PubMedCentralPubMedCrossRef
93.
94.
Santello M, Volterra A. TNFalpha in synaptic function: switching gears. Trends Neurosci. 2012;35(10):638–47.PubMedCrossRef
95.
Vallieres L, et al. Reduced hippocampal neurogenesis in adult transgenic mice with chronic astrocytic production of interleukin-6. J Neurosci. 2002;22(2):486–92.PubMed
96.
Nelson TE, et al. Altered synaptic transmission in the hippocampus of transgenic mice with enhanced central nervous systems expression of interleukin-6. Brain Behav Immun. 2012;26(6):959–71.PubMedCentralPubMedCrossRef
97.
Paolicelli RC, Bisht K, Tremblay ME. Fractalkine regulation of microglial physiology and consequences on the brain and behavior. Front Cell Neurosci. 2014;8:129.PubMedCentralPubMedCrossRef
98.
Schwabe L, et al. Stress impairs spatial but not early stimulus-response learning. Behav Brain Res. 2010;213(1):50–5.PubMedCrossRef
99.
Schwabe L, Wolf OT, Oitzl MS. Memory formation under stress: quantity and quality. Neurosci Biobehav Rev. 2010;34(4):584–91.PubMedCrossRef
100.
Kempermann G, Song H, Gage FH. Neurogenesis in the adult hippocampus. Cold Spring Harb Perspect Biol. 2015;7:a018812.PubMedCrossRef
101.
102.
Koehl M, Abrous DN. A new chapter in the field of memory: adult hippocampal neurogenesis. Eur J Neurosci. 2011;33(6):1101–14.PubMedCrossRef
103.
Amrein I. Adult hippocampal neurogenesis in natural populations of mammals. Cold Spring Harb Perspect Biol. 2015;5:a021295.CrossRef
104.
Aimone JB, Deng W, Gage FH. Resolving new memories: a critical look at the dentate gyrus, adult neurogenesis, and pattern separation. Neuron. 2011;70(4):589–96.PubMedCentralPubMedCrossRef
105.
106.
Leuner B, et al. Learning enhances the survival of new neurons beyond the time when the hippocampus is required for memory. J Neurosci. 2004;24(34):7477–81.PubMedCentralPubMedCrossRef
107.
Cameron HA, McKay RD. Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus. J Comp Neurol. 2001;435(4):406–17.PubMedCrossRef
108.
Ziv Y, et al. Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nat Neurosci. 2006;9(2):268–75.PubMedCrossRef
109.
Opendak M, Gould E. Adult neurogenesis: a substrate for experience-dependent change. Trends Cogn Sci. 2015;19(3):151–61.PubMedCrossRef
110.
111.
Conrad CD. A critical review of chronic stress effects on spatial learning and memory. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(5):742–55.PubMedCrossRef
112.
Kreisel T, et al. Dynamic microglial alterations underlie stress-induced depressive-like behavior and suppressed neurogenesis. Mol Psychiatry. 2014;19(6):699–709.PubMedCrossRef
113.
114.
Whitney NP, et al. Inflammation mediates varying effects in neurogenesis: relevance to the pathogenesis of brain injury and neurodegenerative disorders. J Neurochem. 2009;108(6):1343–59.PubMedCentralPubMedCrossRef
115.
Inoue K, et al. Long-term mild, rather than intense, exercise enhances adult hippocampal neurogenesis and greatly changes the transcriptomic profile of the hippocampus. PLoS One. 2015;10(6):e0128720.PubMedCentralPubMedCrossRef
116.
117.
Suh H, et al. In vivo fate analysis reveals the multipotent and self-renewal capacities of Sox2+ neural stem cells in the adult hippocampus. Cell Stem Cell. 2007;1(5):515–28.PubMedCentralPubMedCrossRef
118.
119.
Smith PJ, et al. Aerobic exercise and neurocognitive performance: a meta-analytic review of randomized controlled trials. Psychosom Med. 2010;72(3):239–52.PubMedCentralPubMedCrossRef
120.
Mouret A, et al. Learning and survival of newly generated neurons: when time matters. J Neurosci. 2008;28(45):11511–6.PubMedCrossRef
121.
Drapeau E, et al. Learning-induced survival of new neurons depends on the cognitive status of aged rats. J Neurosci. 2007;27(22):6037–44.PubMedCrossRef
122.
Winocur G, et al. Inhibition of neurogenesis interferes with hippocampus-dependent memory function. Hippocampus. 2006;16(3):296–304.PubMedCrossRef
123.
Jessberger S, et al. Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats. Learn Mem. 2009;16(2):147–54.PubMedCentralPubMedCrossRef
124.
125.
126.
Lauvsnes MB, et al. Association of hippocampal atrophy with cerebrospinal fluid antibodies against the NR2 subtype of the N-methyl-d-aspartate receptor in patients with systemic lupus erythematosus and patients with primary Sjogren’s syndrome. Arthritis Rheumatol. 2014;66(12):3387–94.PubMedCrossRef
127.
Hanly JG, et al. A prospective analysis of cognitive function and anticardiolipin antibodies in systemic lupus erythematosus. Arthritis Rheum. 1999;42(4):728–34.PubMedCrossRef
128.
Menon S, et al. A longitudinal study of anticardiolipin antibody levels and cognitive functioning in systemic lupus erythematosus. Arthritis Rheum. 1999;42(4):735–41.PubMedCrossRef
129.
Waterloo K, et al. Neuropsychological function in systemic lupus erythematosus: a five-year longitudinal study. Rheumatology (Oxford). 2002;41(4):411–5.CrossRef
130.
Waterloo K, et al. Neuropsychological dysfunction in systemic lupus erythematosus is not associated with changes in cerebral blood flow. J Neurol. 2001;248(7):595–602.PubMedCrossRef
131.
Devinsky O, Petito CK, Alonso DR. Clinical and neuropathological findings in systemic lupus erythematosus: the role of vasculitis, heart emboli, and thrombotic thrombocytopenic purpura. Ann Neurol. 1988;23(4):380–4.PubMedCrossRef
132.
Ellis SG, Verity MA. Central nervous system involvement in systemic lupus erythematosus: a review of neuropathologic findings in 57 cases, 1955–1977. Semin Arthritis Rheum. 1979;8(3):212–21.PubMedCrossRef
133.
Hanly JG, Walsh NM, Sangalang V. Brain pathology in systemic lupus erythematosus. J Rheumatol. 1992;19(5):732–41.PubMed
134.
Scolding NJ, Joseph FG. The neuropathology and pathogenesis of systemic lupus erythematosus. Neuropathol Appl Neurobiol. 2002;28(3):173–89.PubMedCrossRef
135.
Yajima N, et al. Elevated levels of soluble fractalkine in active systemic lupus erythematosus: potential involvement in neuropsychiatric manifestations. Arthritis Rheum. 2005;52(6):1670–5.PubMedCrossRef
136.
Hirohata S, Miyamoto T. Elevated levels of interleukin-6 in cerebrospinal fluid from patients with systemic lupus erythematosus and central nervous system involvement. Arthritis Rheum. 1990;33(5):644–9.PubMedCrossRef
137.
Trysberg E, Carlsten H, Tarkowski A. Intrathecal cytokines in systemic lupus erythematosus with central nervous system involvement. Lupus. 2000;9(7):498–503.PubMedCrossRef
138.
Alcocer-Varela J, Aleman-Hoey D, Alarcon-Segovia D. Interleukin-1 and interleukin-6 activities are increased in the cerebrospinal fluid of patients with CNS lupus erythematosus and correlate with local late T-cell activation markers. Lupus. 1992;1(2):111–7.PubMedCrossRef
139.
Katsumata Y, et al. Diagnostic reliability of cerebral spinal fluid tests for acute confusional state (delirium) in patients with systemic lupus erythematosus: interleukin 6 (IL-6), IL-8, interferon-alpha, IgG index, and Q-albumin. J Rheumatol. 2007;34(10):2010–7.PubMed
140.
George-Chandy A, Trysberg E, Eriksson K. Raised intrathecal levels of APRIL and BAFF in patients with systemic lupus erythematosus: relationship to neuropsychiatric symptoms. Arthritis Res Ther. 2008;10(4):R97.PubMedCentralPubMedCrossRef
141.
Fragoso-Loyo H, et al. Interleukin-6 and chemokines in the neuropsychiatric manifestations of systemic lupus erythematosus. Arthritis Rheum. 2007;56(4):1242–50.PubMedCrossRef
142.
Trysberg E, et al. Neuronal and astrocytic damage in systemic lupus erythematosus patients with central nervous system involvement. Arthritis Rheum. 2003;48(10):2881–7.PubMedCrossRef
143.
Trysberg E, et al. Intrathecal levels of matrix metalloproteinases in systemic lupus erythematosus with central nervous system engagement. Arthritis Res Ther. 2004;6(6):R551–6.PubMedCentralPubMedCrossRef
144.
Hsu TC, et al. Beneficial effects of treatment with cystamine on brain in NZB/W F1 mice. Eur J Pharmacol. 2008;591(1–3):307–14.PubMedCrossRef
145.
Tomita M, Holman BJ, Santoro TJ. Aberrant cytokine gene expression in the hippocampus in murine systemic lupus erythematosus. Neurosci Lett. 2001;302(2–3):129–32.PubMedCrossRef
146.
McLean BN, Miller D, Thompson EJ. Oligoclonal banding of IgG in CSF, blood-brain barrier function, and MRI findings in patients with sarcoidosis, systemic lupus erythematosus, and Behcet’s disease involving the nervous system. J Neurol Neurosurg Psychiatry. 1995;58(5):548–54.PubMedCentralPubMedCrossRef
147.
Nishimura K, et al. Blood-brain barrier damage as a risk factor for corticosteroid-induced psychiatric disorders in systemic lupus erythematosus. Psychoneuroendocrinology. 2008;33(3):395–403.PubMedCrossRef
148.
Bertsias GK, Boumpas DT. Pathogenesis, diagnosis and management of neuropsychiatric SLE manifestations. Nat Rev Rheumatol. 2010;6(6):358–67.PubMedCrossRef
149.
150.
151.
Hirohata S, et al. Blood-brain barrier damages and intrathecal synthesis of anti-N-methyl-d-aspartate receptor NR2 antibodies in diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus. Arthritis Res Ther. 2014;16(2):R77.PubMedCentralPubMedCrossRef
152.
Sled JG, et al. Time course and nature of brain atrophy in the MRL mouse model of central nervous system lupus. Arthritis Rheum. 2009;60(6):1764–74.PubMedCrossRef
153.
Abbott NJ, Mendonca LL, Dolman DE. The blood-brain barrier in systemic lupus erythematosus. Lupus. 2003;12(12):908–15.PubMedCrossRef
154.
O’Carroll SJ, et al. Pro-inflammatory TNFalpha and IL-1beta differentially regulate the inflammatory phenotype of brain microvascular endothelial cells. J Neuroinflammation. 2015;12:131.PubMedCentralPubMedCrossRef
155.
156.
Rekvig OP, et al. Autoantibodies in lupus: culprits or passive bystanders? Autoimmun Rev. 2012;11(8):596–603.PubMedCrossRef
157.
Jeltsch-David H, Muller S. Neuropsychiatric systemic lupus erythematosus: pathogenesis and biomarkers. Nat Rev Neurol. 2014;10(10):579–96.PubMedCrossRef
158.
Hu C, et al. Autoantibody profiling on human proteome microarray for biomarker discovery in cerebrospinal fluid and sera of neuropsychiatric lupus. PLoS One. 2015;10(5):e0126643.PubMedCentralPubMedCrossRef
159.
160.
Faust TW, et al. Neurotoxic lupus autoantibodies alter brain function through two distinct mechanisms. Proc Natl Acad Sci USA. 2010;107(43):18569–74.PubMedCentralPubMedCrossRef
161.
162.
163.
Chang EH, et al. Selective impairment of spatial cognition caused by autoantibodies to the N-Methyl-d-Aspartate receptor. EBioMedicine. 2015;2(7):755–64.PubMedCentralPubMedCrossRef
164.
Omdal R, et al. Neuropsychiatric disturbances in SLE are associated with antibodies against NMDA receptors. Eur J Neurol. 2005;12(5):392–8.PubMedCrossRef
165.
Arinuma Y, Yanagida T, Hirohata S. Association of cerebrospinal fluid anti-NR2 glutamate receptor antibodies with diffuse neuropsychiatric systemic lupus erythematosus. Arthritis Rheum. 2008;58(4):1130–5.PubMedCrossRef
166.
Fragoso-Loyo H, et al. Serum and cerebrospinal fluid autoantibodies in patients with neuropsychiatric lupus erythematosus. Implications for diagnosis and pathogenesis. PLoS One. 2008;3(10):e3347.PubMedCentralPubMedCrossRef
167.
Yoshio T, et al. Association of IgG anti-NR2 glutamate receptor antibodies in cerebrospinal fluid with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum. 2006;54(2):675–8.PubMedCrossRef
168.
Massardo L, et al. Anti-N-methyl-d-aspartate receptor and anti-ribosomal-P autoantibodies contribute to cognitive dysfunction in systemic lupus erythematosus. Lupus. 2015;24(6):558–68.PubMedCrossRef
169.
Mackay M, et al. Brain metabolism and autoantibody titres predict functional impairment in systemic lupus erythematosus. Lupus Sci Med. 2015;2(1):e000074.PubMedCentralPubMedCrossRef
170.
Elkon KB, Parnassa AP, Foster CL. Lupus autoantibodies target ribosomal P proteins. J Exp Med. 1985;162(2):459–71.PubMedCrossRef
171.
Briani C, et al. Neurolupus is associated with anti-ribosomal P protein antibodies: an inception cohort study. J Autoimmun. 2009;32(2):79–84.PubMedCrossRef
172.
Hirohata S, et al. Association of cerebrospinal fluid anti-ribosomal p protein antibodies with diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus. Arthritis Res Ther. 2007;9(3):R44.PubMedCentralPubMedCrossRef
173.
Karassa FB, et al. Accuracy of anti-ribosomal P protein antibody testing for the diagnosis of neuropsychiatric systemic lupus erythematosus: an international meta-analysis. Arthritis Rheum. 2006;54(1):312–24.PubMedCrossRef
174.
Hanly JG, et al. Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus. Ann Rheum Dis. 2011;70(10):1726–32.PubMedPubMedCentralCrossRef
175.
Reichlin M. Autoantibodies to the ribosomal P proteins in systemic lupus erythematosus. Clin Exp Med. 2006;6(2):49–52.PubMedCrossRef
176.
Matus S, et al. Antiribosomal-P autoantibodies from psychiatric lupus target a novel neuronal surface protein causing calcium influx and apoptosis. J Exp Med. 2007;204(13):3221–34.PubMedCentralPubMedCrossRef
177.
Segovia-Miranda F, et al. Pathogenicity of lupus anti-ribosomal P antibodies: role of cross-reacting neuronal surface P antigen in glutamatergic transmission and plasticity in a mouse model. Arthritis Rheumatol. 2015;67(6):1598–610.PubMedCrossRef
178.
Bravo-Zehnder M, et al. Anti-ribosomal P protein autoantibodies from patients with neuropsychiatric lupus impair memory in mice. Arthritis Rheumatol. 2015;67(1):204–14.PubMedCrossRef
179.
Katzav A, et al. Anti-P ribosomal antibodies induce defect in smell capability in a model of CNS -SLE (depression). J Autoimmun. 2008;31(4):393–8.PubMedCrossRef
Metadata
Title
Lupus brain fog: a biologic perspective on cognitive impairment, depression, and fatigue in systemic lupus erythematosus
Author
Meggan Mackay
Publication date
01-12-2015
Publisher
Springer US
Published in
Immunologic Research / Issue 1-3/2015
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-015-8716-3

Other articles of this Issue 1-3/2015

Immunologic Research 1-3/2015 Go to the issue

AUTOIMMUNITY/IMMUNOREGULATION/INFLAMMATION

The Genotype and Phenotype (GaP) registry: a living biobank for the analysis of quantitative traits

AUTOIMMUNITY/IMMUNOREGULATION/INFLAMMATION

Age-dependent alterations in the inflammatory response to pulmonary challenge

AUTOIMMUNITY/IMMUNOREGULATION/INFLAMMATION

The erythroblastic island as an emerging paradigm in the anemia of inflammation

AUTOIMMUNITY/IMMUNOREGULATION/INFLAMMATION

Chronic intermittent hypoxia exposure-induced atherosclerosis: a brief review

AUTOIMMUNITY

A pilot study to determine the optimal timing of the Physician Global Assessment (PGA) in patients with systemic lupus erythematosus

AUTOIMMUNITY

Advancing drug delivery systems for the treatment of multiple sclerosis