Académique Documents
Professionnel Documents
Culture Documents
Erythematosus . Introduction
Article Contents
Peter H Schur, Brigham and Womens Hospital, Boston, Massachusetts, USA . Constitutional Symptoms
. Fatigue
. Prognosis
Weight changes
Lupus may be associated with weight loss and weight gain.
Weight loss often occurs before the diagnosis of SLE is
ELS subject area: Immunology made. Unintentional weight loss may be due to decreased
appetite, the side eects of medications, gastrointestinal
How to cite: disease or the use of diuretics. See also: Hypothalamic
Schur, Peter H (March 2009) Systemic Lupus Erythematosus. In:
Control of Food Intake and Body Weight
Encyclopedia of Life Sciences (ELS). John Wiley & Sons, Ltd: Chichester.
DOI: 10.1002/9780470015902.a0002147.pub2
Weight gain in SLE is usually due to one of the two
factors: salt and water retention associated with the
ENCYCLOPEDIA OF LIFE SCIENCES & 2009, John Wiley & Sons, Ltd. www.els.net 1
Systemic Lupus Erythematosus
2 ENCYCLOPEDIA OF LIFE SCIENCES & 2009, John Wiley & Sons, Ltd. www.els.net
Systemic Lupus Erythematosus
and renal biopsy is useful to dene the type and degree of tomography, bronchoalveolar lavage and/or biopsy. Acute
inammation and scarring. See also: Glomerulonephritis pneumonitis can be fatal if untreated, but often becomes
Mesangial (type II) nephritis occurs in 1020% of cases. chronic, leading to pulmonary insuciency.
Immune deposits are detected primarily in the mesangium; Pulmonary hypertension is uncommon, and often un-
there are some minor urine (e.g. red cells, white cells, pro- recognized until detected too late. Patients may have some
tein) and serological (e.g. raised antideoxyribonucleic acid dyspnoea and chest pain, often detected by chance on
(DNA) antibodies and low complement levels) abnormal- echocardiography. When moderate to severe, the progno-
ities. Hypertension is uncommon; progression to renal sis is very poor. See also: Pulmonary Hypertension
failure is virtually never seen. Rare complications include the shrinking lung syndrome
Focal proliferative (type III) nephritis occurs in 1020% and pulmonary haemorrhage.
of patients. Histologically there are focal areas of
glomerular proliferation. There are signicant urinary Cardiovascular
and serological abnormalities, but hypertension and pro-
gression to renal insuciency are uncommon. Pericarditis is relatively common, although usually clini-
Diuse proliferative (type IV) nephritis is the most com- cally insignicant. Verrucous endocarditis (LibmanSacks
mon form. There are signicant urinary and serological disease) is usually clinically silent but can produce valvular
abnormalities, as well as hypertension and azotaemia. insuciency and serve as a source of emboli. Both are
There is considerable inammation and/or scarring of the usually detected by echocardiography. See also: Cardio-
glomeruli, as determined by pathological ndings. Un- vascular Disease: Epidemiology
treated, this usually progresses to renal failure. There is an increasing frequency of coronary artery dis-
Membranous (type V) nephritis also aects approxi- ease, as patients live longer, are treated with high-dose
mately 1020% of patients, who show peripheral oedema steroids, become hypertensive and are hyperlipaemic.
and signicant proteinuria, without other urine or sero-
logical abnormalities. Blood pressure is usually normal; Central nervous system
azotaemia is absent. Pathologically the basement mem-
Neurological and psychiatric complications occur in most
brane is thickened. The prognosis for survival is good with
patients. They may result directly from SLE, or from com-
appropriate therapy.
plications of the disease (e.g. hypertension, uraemia) and its
treatment. The most common neurological complications
Gastrointestinal tract are cognitive defects, usually characterized by memory
problems. In addition, patients may have generalized or
The gastrointestinal tract is often involved, manifesting with
partial complex seizures, strokes (usually due to thrombo-
abdominal pain. However, this is more commonly from the
sis) and peripheral neuropathy. Headaches are very com-
side eects of medication than from active SLE. Examples of
mon. As a result of brain involvement, or because of a
the former include gastritis and even peptic ulceration sec-
psychological reaction to this chronic potentially fatal dis-
ondary to the use of nonsteroidal anti-inammatory drugs
ease, patients often develop anxiety and/or depression.
(NSAIDs) and/or corticosteroids. However, SLE (mesen-
Complications include seizures due to uraemia, strokes
teric artery) vasculitis can lead to pancreatitis, peritonitis
from hypertension and meningitis (infectious or secondary
and colitis. Liver involvement from lupus is unusual and
to medications). The diagnosis is often assisted by electro-
presentation with liver function abnormalities and a positive
encephalography, MRI of the brain and/or examination of
antinuclear antibody (ANA) test result is more consistent
spinal uid. See also: Headache
with chronic active hepatitis (lupoid hepatitis).
Haematological
Pulmonary
Patients with SLE frequently develop abnormalities in each
Chest pain on breathing occurs in approximately 50% of of the three blood cell lines:
patients with SLE. This is usually due to chest wall muscle
pain, without inammation. The pain is aggravated by . Leucopenia is common. While diagnostically useful, it is
touch and/or movement. However, there may be inam- usually not symptomatic (predisposing to infection) un-
mation of the pleura (pleuritis), which causes pain on less severe.
breathing. Pleuritis is said to occur in approximately 50% . Many patients have mild anaemia, usually as a result of
of patients with lupus. It is often associated with a pleural the anaemia of chronic disease. Haemolytic anaemia is
eusion, which is usually small and mildly inammatory. rare, but can be very severe. See also: Anaemia: Overview
Approximately 10% of patients with SLE develop a . Thrombocytopenia is also frequently seen, although
pneumonitis characterized by fever, even haemoptysis, bleeding usually occurs only with platelet counts below
pleurisy, dyspnoea and pulmonary inltrates on chest ra- 25 000 mm3.
diography. Infection must be excluded. Pathologically,
there is a severe alveolitis with both neutrophils and mono- Other ndings include hypocomplementaemia and an
nuclear cells. Diagnosis may be facilitated by computed increase in the erythrocyte sedimentation rate, g-globulin
ENCYCLOPEDIA OF LIFE SCIENCES & 2009, John Wiley & Sons, Ltd. www.els.net 3
Systemic Lupus Erythematosus
4 ENCYCLOPEDIA OF LIFE SCIENCES & 2009, John Wiley & Sons, Ltd. www.els.net
Systemic Lupus Erythematosus
Table 2 American Rheumatologic Association criteria for diagnosis of systemic lupus erythematosus
Criterion Denition
Malar rash Fixed erythema, at or raised, over the malar eminences; tending to spare the nasolabial
folds
Discoid rash Erythematous raised patches with adherent keratotic scaling and follicular plugging;
atrophic scarring may occur in older lesions
Photosensitivity Skin rash as a result of unusual reaction to sunlight; causation established by patient history
or physician observation
Oral ulcers Oral or nasopharyngeal ulceration, usually painless, observed by a physician
Arthritis Nonerosive arthritis involving two or more peripheral joints, characterized by tenderness,
swelling or eusion
Serositis Pleuritis with convincing history of pleuritic pain or rub heard by a physician, or evidence of
pleural eusion; or pericarditis documented by electrocardiogram, rub or evidence of
pericardial eusion
Renal disorder Persistent proteinuria greater than 0.5 g day21, or greater than 3 g day21 if quantitation not
performed; or cellular casts which may be red cell, haemoglobin, granular, tubular or mixed
Neurological disorder Seizures or psychosis in the absence of oending drugs or known metabolic derangements
(uraemia, ketoacidosis or electrolyte imbalance)
Haematological disorder Haemolytic anaemia with reticulocytosis; or leucopenia with less than 4000 cells per mm3
total on two or more occasions; or lymphopenia with less than 1500 cells per mm3 on two or
more occasions; or thrombocytopenia with less than 100 000 platelets per mm3 in the absence
of oending drugs
Immunological disorder Positive for antiphospholipid antibody; or presence of anti-DNA antibody (antibody to
native DNA) present in abnormal titre; or presence of anti-Sm antibody (antibody to Sm
nuclear antigen); or false positive serological test for syphilis, known to be positive for at
least 6 months and conrmed by Treponema pallidum immobilization or uorescent
treponemal antibody absorption test
Antinuclear antibody An abnormal titre of antinuclear antibody by immunouorescence, or an equivalent assay,
at any point in time and in the absence of drugs known to be associated with drug-induced
lupus syndrome
Other autoantibodies are associated with specic clinical and thrombophlebitis) and in placental infarcts (causing
manifestations: miscarriage). Antiphospholipid antibodies are detected by
three tests: Lupus anticoagulant, anticardiolipin and anti-
. antibodies to single-stranded DNA and nucleosomes,
bodies to b2-glycoprotein I.
found frequently in SLE, rheumatoid arthritis and other
rheumatic diseases
. antibodies to ribonucleoprotein (RNP) in SLE, MCTD,
RA, Raynauds and scleroderma Epidemiology
. antibodies to Ro (SS-A) and La (SS-B) in SLE and
Sjogren syndrome The reported prevalence of SLE in the population is 40150
. anti-dsDNA with lupus nephritis cases per 100 000. There is an increased frequency of SLE
. anti-Ro with photosensitivity, neonatal lupus, C2 de- among women that has been thought to be due to an oes-
ciency and subacute cutaneous lupus trogen hormonal eect (see the section on Hormonal fac-
. anti-ribosomal P protein with lupus psychosis, cerebritis tors). This oestrogenic eect has been thought to explain
and/or depression. the female-to-male ratio of SLE in dierent age groups: in
children, in whom sex hormonal eects are presumably
minimal, the female-to-male ratio is approximately 3:1; in
Antiphospholipid antibodies adults the ratio ranges from 10 to 15:1; in older individuals
Patients with SLE may form antibodies to phospholipids the ratio is approximately 8:1. Sixty-ve per cent of patients
including a phospholipidb2-glycoprotein I complex. with SLE have disease onset between the ages of 16 and 55
b2-glycoprotein I normally has an anticoagulant eect that years. However, other possibilities for female predisposi-
is diminished by this antibody formation. This may explain tion have been suggested including X-inactivation, X- or
why antiphospholipid antibodies are implicated in the aeti- Y-chromosome genetic modulation and other factors
ology of arterial and venous thrombosis (causing strokes (Lockshin, 2006). See also: Sex Hormones in Vertebrates
ENCYCLOPEDIA OF LIFE SCIENCES & 2009, John Wiley & Sons, Ltd. www.els.net 5
Systemic Lupus Erythematosus
6 ENCYCLOPEDIA OF LIFE SCIENCES & 2009, John Wiley & Sons, Ltd. www.els.net
Systemic Lupus Erythematosus
programmed cell death (Graham and Utz, 2005). Apopto- UV light may stimulate keratinocytes to express more
tic cells are also poorly cleared in SLE, although anti- small nuclear ribonucleoproteins (snRNPs) on their cell
phospholipid antibodies enhance opsonization and surface, and to secrete more IL-1, IL-3, IL-6, gran-
clearance. The act of phagocytosis results in stimulation ulocytemacrophage colony-stimulating factor (GM-
of the immune response to autoantigens derived from the CSF) and tumour necrosis factor a (TNFa), thereby
apoptotic cells. See also: Apoptosis: Molecular Mechan- stimulating B cells to make more antibody. In addition
isms; Phagocytosis to the local eects in skin, UV light may also increase
These multiple defects cause a cascade of events that the degree of systemic autoimmunity by interfering with
begins with abnormal cellular breakdown and ends with antigen processing by and activation of macrophages.
the production of autoantibodies. As cells break down ab- UV light decreases T-cell DNA methylation, which may
normally, certain antigens (especially nuclear and cryptic lead to overexpression of lymphocyte function-associated
self-peptides) are processed, perhaps abnormally, into pep- antigen (LFA) 1. These T cells may then become auto-
tides by antigen-presenting cells (APCs) such as macro- reactive, resulting in autoantibody formation. See also:
phages, B lymphocytes and dendritic cells. Alternatively, Antigen Processing
microorganisms may be broken down within APCs into
mimicry peptides that have sucient structural similarity
with immunodominant self-peptides. See also: Antigen-
presenting Cells; Molecular Mimicry Pathogenesis of Clinical
With either mechanism, a peptidemajor histocom-
patibility complex (MHC) forms and stimulates the ac- Manifestations
tivation and clonal expansion of CD4+ autoreactive T
cells. These cells, via release of cytokines (e.g. IL-4, IL-6 Although the exact aetiology of SLE remains obscure, it
and IL-10) (Kyttaris et al., 2005), cause autoreactive B is clear that many of the clinical manifestations of SLE
cells to become activated to proliferate and dierentiate are mediated directly or indirectly by antibody formation
into antibody-producing cells that make an excess of and the creation of immune complexes. As an example,
antibodies to many nuclear antigens. Thus, a specic immune complex deposition in the kidney is responsible
immune prole develops that is characterized by the de- for much of the tissue damage of lupus nephritis. These
velopment of raised levels of ANA, especially to DNA, complexes form either in the circulation, where they
Sm, RNP, Ro, La, nucleosomes and other nuclear an- are poorly cleared, or in situ, as free antibody binds to
tigens. See also: Major Histocompatibility Complex: free antigen that has already deposited in the glomerulus
Interaction with Peptides or is an intrinsic glomerular antigen. Once deposited,
ANAs are made to antigens from active sites on mole- immune complexes activate the complement system,
cules involved in essential cellular functions (such as RNA thereby generating chemotactic factors that attract leu-
splicing). With continued pressure over time from self- cocytes and mononuclear cells. These cells phagocytose
antigens, the immune response switches, via somatic immune complexes and release mediators (such as
(hyper)mutation, from low-anity highly cross-reactive cytokines and activators of the clotting system) that per-
immunoglobulin (Ig) M antibodies to high-anity IgG petuate the glomerular inammation. With continuing
antibodies, and then nally to antibodies directed towards immune complex deposition, chronic inammation may
more limited epitopes on self-antigens. Unique idiotypes of ensue, ultimately leading to brinoid necrosis, scarring
antibodies may then stimulate autoreactive T cells to ex- and reduced renal function. See also: AntigenAntibody
pand, thereby helping unique clones of B cells to expand. Complexes; Immune Complex Disease
The nal result is the production of more specic ANAs Immune complexes have also been detected (by
with unique idiotypes. See also: Antibody Responses: immunouorescence and/or electron microscopy) at the
Development; B Lymphocytes; Somatic Hypermutation in dermalepidermal junction in skin lesions, the choroid
Antibody Evolution plexus, the pericardium and the pleural cavity.
The rate at which immune complexes are cleared by Fc
receptors on monocytesmacrophages in the liver and
spleen from the circulation may be genetically impaired in
Environmental factors patients with SLE. See also: Fc Receptors
The environment may have a role in the aetiology of SLE
via its eects on the immune system.
Viruses, for example, may stimulate specic cells in this
immune network. Patients with SLE have higher titres of Treatment
antibodies to EpsteinBarr virus and make antibodies to
retroviruses, including protein regions homologous with Eective treatment requires ongoing patientdoctor com-
HLA antigens. Antibodies to these molecular mimicry munication to interpret laboratory tests correctly, alleviate
molecules may contribute to the development of autoim- symptoms, prevent and treat relapses, and lessen side
munity. See also: EpsteinBarr Virus; Molecular Mimicry eects related to drug therapy.
ENCYCLOPEDIA OF LIFE SCIENCES & 2009, John Wiley & Sons, Ltd. www.els.net 7
Systemic Lupus Erythematosus
8 ENCYCLOPEDIA OF LIFE SCIENCES & 2009, John Wiley & Sons, Ltd. www.els.net
Systemic Lupus Erythematosus
exacerbations and should therefore be avoided. In contrast, medications that deplete B lymphocytes (e.g. rituximab,
medications that cause drug-induced lupus, such as pro- epratuzumab) and one that activates the B-cell factors
cainamide and hydralazine, do not cause exacerbations of APRIL (B cell proliferation inducing ligand) and B cell
idiopathic SLE. This observation is a presumed reection of activating factor (BAFF)/B lymphocyte stimulator (BLyS)
the pathogenetic dierences between the two disorders. (atacicept) (Tieng and Peeva, 2008). Furthermore, many
more agents that aect tolerance, B cells, chemokines,
cytokines, inammation and innate immunity (including
Pregnancy and contraception
TLRs) are being studied in animal (e.g. mouse) models of
Pregnancy should be avoided during active disease (espe- SLE (Davidson and Aranow, 2006). By contrast, anti-TNF
cially with signicant organ impairment) due to the high risk biologics, which are so eective in the treatment of rheu-
of miscarriage. Women with SLE should be counselled not matoid arthritis, have been avoided in the treatment of
to become pregnant until the disease has been quiescent for SLE, because they frequently cause a drug-induced lupus
at least 6 months. See also: Pregnancy: Maternal Disorders syndrome.
Oral contraceptives containing high-dose oestrogens can
cause exacerbations of SLE. However, this complication
rarely occurs with the current use of low-dose oestrogen- or
progesterone-containing compounds. Patients with mi-
Prognosis
graine headaches, Raynaud syndrome, a history of phle-
SLE can run a varied clinical course, ranging from a relatively
bitis or antiphospholipid antibodies probably should not
benign illness to a rapidly progressive disease with fulminant
take oral estrogen-containing contraceptives.
organ failure and death. Most patients have a relapsing and
Pregnant patients with active lupus are generally man-
remitting course, which is usually managed with the use of
aged with corticosteroids. Other drugs used during
high-dose steroids during the treatment of severe ares.
pregnancy include NSAIDs and hydroxychloroquine
(probably safe). Cyclophosphamide, mycophenolate and
Patient survival
methotrexate are contraindicated; however, azathioprine
can be used cautiously. The survival rate of patients with SLE has increased dra-
matically over the past several decades, from approximately
Treatment of specific organ involvement 40% at 5 years in the 1950s to approximately 90% at 15 years
at the present time. The likelihood of survival can be ranked
A number of medications are commonly used in the treat- on the basis of organ involvement (skin and musculoskeletal
ment of SLE, including NSAIDs, antimalarials (primarily are highest; CNS and renal are lowest) and on the number of
hydroxychloroquine), corticosteroids (primarily prednis- American College of Rheumatology criteria for SLE present
one) and immunosuppressive agents (primarily cyclo- (the higher the number, the worse the prognosis).
phosphamide, mycophenolate and azathioprine). What The improvement in patient survival is probably a result
follows is a general overview of which drugs are preferred in of multiple factors. These include increased disease recog-
selected clinical settings. nition with more sensitive diagnostic tests, earlier diagnosis
NSAIDs are generally eective for musculoskeletal or treatment, the inclusion of milder cases, and increasingly
complaints and mild serositis. Antimalarials are most use- judicious therapy and prompt treatment of complications.
ful for skin manifestations and for musculoskeletal com- The major cause of death in the rst few years of illness is
plaints that do not adequately respond to NSAIDs. active disease (e.g. CNS, renal or cardiovascular disease),
See also: History of Antimalarial Agents whereas late deaths are caused either by the illness or by
Systemic corticosteroids used alone or in combination treatment complications (including infection and coronary
with immunosuppressive agents are reserved for patients disease).
with signicant organ involvement, particularly renal, Serious infection is most often due to immunosuppres-
CNS disease and haematological manifestations. See also: sive therapy. Patients at particular risk are those treated
Immunosuppressive Drugs with both corticosteroids and immunosuppressives, espe-
Treatment with prednisone as soon as a signicant rise in cially if the white blood cell count is less than 3000 mL21
anti-dsDNA occurred prevented relapses in most cases in a and/or high-dose steroids are given.
study of 156 patients (Bootsma et al., 1995). The present Premature coronary artery disease is being increasingly
author follows such patients closely but does not treat titres recognized as a cause of late mortality; this has been at-
in the absence of clinical evidence of active disease. See also: tributed primarily to accelerated atherosclerosis associated
Autoimmune Disease: Treatment with corticosteroid use (Karp et al., 2008). See also:
Cardiovascular Disease: Epidemiology
The relation of SLE to cancer is unclear because con-
New Biologic Therapies icting data have been reported. Multiple studies have
found either no change, an increase, or a decrease in the
A number of newer immunosuppressive agents are being cancer rate, a decrease in cancer rate but an increase in non-
investigated in formal therapeutic trials. These include Hodgkin lymphoma (Bernatsky et al., 2006). The largest
ENCYCLOPEDIA OF LIFE SCIENCES & 2009, John Wiley & Sons, Ltd. www.els.net 9
Systemic Lupus Erythematosus
study of 1585 Danish patients with SLE found a 5-fold 10-year period. A comparison of early and late manifestations
increase in the risk of non-Hodgkin lymphoma, as well as in a cohort of 1,000 patients. Medicine (Baltimore) 82: 299.
an increase in lung, liver and vaginalvulval cancer. Davidson A and Aranow C (2006) Pathogenesis and treatment of
See also: Non-Hodgkin Lymphomas systemic lupus erythematosus nephritis. Current Opinion in
Rheumatology 18: 468475.
Poor prognosis for survival in SLE includes: Drenkard C, Villa AR, Garcia-Padilla C et al. (1996) Remission of
systemic lupus erythematosus. Medicine 75: 8898.
. renal disease (especially diuse proliferative glomerulo- Feng X, Wu H, Grossman JM et al. (2006) Association of in-
nephritis); creased interferon-inducible gene expression with disease ac-
. hypertension; tivity and lupus nephritis in patients with systemic lupus
. male sex; erythematosus. Arthritis and Rheumatism 54: 2951.
. young age; Graham KL and Utz PJ (2005) Sources of autoantigens in sys-
. older age at presentation; temic lupus erythematosus. Current Opinion in Rheumatology
. black race, which may primarily reect low socio- 17: 513.
economic status; Grimaldi CM (2006) Sex and systemic lupus erythematosus: the
. poor socioeconomic status; role of the sex hormones estrogen and prolactin on the regu-
. presence of antiphospholipid antibodies and lation of autoreactive B cells. Current Opinion in Rheumatology
. high overall disease activity. 18: 456461.
Hahn BH, Ebling F, Singh RR et al. (2005) Cellular and molecular
mechanisms of regulation of autoantibody production in lupus.
Annals of the New York Academy of Sciences 1051: 433.
Morbidity Heller CA and Schur PH (1985) Serological and clinical remission
in SLE. Journal of Rheumatology 12: 916918.
Despite the reduction in long-term mortality, patients with Hochberg MC (1997) Updating the American College of Rheu-
SLE are still at risk for signicant morbidity due to both matology Revised criteria for the classication of systemic lupus
active disease and the side eects of drugs such as cortico- erythematosus. Arthritis and Rheumatism 40: 1725.
steroids and immunosuppressive agents. Steroid-induced Kamen DA and Aranow CB (2008) Vitamin D in Systemic Lupus
avascular necrosis of the hips and knees has become a par- Erythematosus. Current Opinion in Rheumatology 20: 532537.
ticularly important problem as patients live longer with the Karp I, Abrahamowicz M, Fortin PR et al. (2008) Recent cor-
illness. ticosteroid use and recent disease activity: independent deter-
minants of coronary heart disease risk factors in systemic lupus
erythematosus? Arthritis and Rheumatism 59: 169.
Remission
King JK and Hahn BH (2007) Systemic lupus erythematosus:
Although a major focus has been on improving mortality modern straegies for management a moving target. Best
and morbidity rates in SLE, it is becoming increasingly Practice & Research Clinical Rheumatology 21: 971987.
recognized that many patients have a clinical remission Kyttaris VC, Juang YT and Tsokos GC (2005) Immune cells and
requiring no treatment. In a recent study of 667 patients, cytokines in systemic lupus erythematosus: an update. Current
approximately 25% had treatment-free remission lasting Opinion in Rheumatology 17: 518.
for at least 1 year (Drenkard et al., 1996). Remission oc- Lahita RG (1990) Sex hormones and the immune system. Part 1.
Human data. Baillie`res Clinical Rheumatology 4: 112.
curred in 50% of those with disease of more than 18 years
Lockshin MD (2006) Sex dierences in autoimmune disease.
duration, and in 75% of those with disease of over 30 years
Lupus 15: 753.
duration. Remission was also seen in some patients who
Migita K, Miyashita T, Maeda Y et al. (2007) Toll-like receptor
had severe renal disease. In another report, 6% of 300 pa- expression in lupus peripheral blood mononuclear cells. Journal
tients went into long-lasting clinical and serological remis- of Rheumatology 34: 493.
sion (i.e. a negative ANA test result) (Heller and Schur, Papadimitraki ED, Choulaki C, Koutala E et al. (2006) Expan-
1985). sion of toll-like receptor 9-expressing B cells in active systemic
lupus erythematosus: implications for the induction and main-
tenance of the autoimmune process. Arthritis and Rheumatism
References 54: 3601.
Pugh-Bernard AE and Cambier JC (2006) B cell receptor signal-
Allam R and Anders H-J (2008) The role of innate immunity in ling in human systemic lupus erythematosus. Current Opinion in
autoimmune tissue injury. Current Opinion in Rheumatology 20: Rheumatology 18: 451455.
538544. Ronnblom L and Pascual V (2008) The innate immune system in
Bernatsky S, Boivin JF, Joseph L et al. (2006) Mortality in sys- SLE: type I interferons and dendritic cells. Lupus 17: 394399.
temic lupus erythematosus. Arthritis and Rheumatism 54: 2550. Schur PH (1995) Genetics of systemic lupus erythematosus. Lupus
Bootsma H, Spronk P, Derksen R et al. (1995) Prevention of 4: 425437.
relapses in SLE. Lancet 345: 15951599. Sestak AL, Nath SK, Sawalha AH and Harley JB (2007) Current
Cervera R, Khamashta MA, Font J et al. (2003) Morbidity status of lupus genetics. Arthritis Research & Therapy 9: 210
and mortality in systemic lupus erythematosus during a 219.
10 ENCYCLOPEDIA OF LIFE SCIENCES & 2009, John Wiley & Sons, Ltd. www.els.net
Systemic Lupus Erythematosus
ENCYCLOPEDIA OF LIFE SCIENCES & 2009, John Wiley & Sons, Ltd. www.els.net 11