SLE Flashcards
Who are at the most risk for SLE
Women (9:1 ratio to men) (especially in REPRODUCTIVE years)
African, Native and Hispanic American
Examples of Autoimmune diseases
Hashimotos (thyroid) Multiple Sclerosis (CNS) Pernicious Anemia (stomach) Addisons (adrenal) DM Type 1 (pancreas) Pemphigus Vulgaris (skin) Pleuritis* Pericarditis* Glomerulonephritis* Raynaud Phenomenon* Arthritis*
*Systemic
Examples of Immune Dysregulation involved with SLE
B-cells: defective selection and autoantibody production
T-cells: Inc. Th17 and dec. Tregs
Dendritic cells: lots of Interferon and activate autoreactive T/B cells
(Natural/Pathogenic) autoantibodies involve IgM effectively clear cellular debris in healthy individuals
Natural
(Natural/Pathogenic) autoantibodies involve IgG to form immune complexes and directly target cells through cross-reactivity with other antigens
Pathogenic
HALLMARK autoantibodies for SLE; SENSITIVE, not specific, because it is seen in many autoimmune disorders and some healthy patients; Autoantibodies against various components of the cell nucleus; best seen with Immunofluorescence
Anti-nuclear Antibodies
ANA are (sensitive/specific) for SLE
Sensitive (nearly all of SLE patients have it, but so do many other autoimmune diseases)
Autoimmune diseases that are associated with Anti-Nuclear Antibodies
SLE (99%) Scleroderma (95%) Hashimotos (50%) IPF (50%) Normal Patients (4%)
Best detection method for Anti-Nuclear Antibodies
Immunofluorescence
Anti-DNA and Smith antibodies are highly (sensitive/specific) for SLE
Specific
SPECIFIC autoantibody for SLE; is highly associated with NEPHRITIS
Anti-ds DNA
Autoantibody for SLE; highly associated with Sicca and Neonatal Lupus
Anti-SSA (Ro)
Autoantibody for SLE; highly associated with Arthritis, Myositis and Lung Disease
Anti-RNP
Methods for detecting Anti-ds DNA antibodies
Crithidia assay (kinetoplast with dsDNA) (specific) Farr Assay (sensitive)
Signs/Symptoms of SLE
Malar rash (cheeks and nose) Discoid rash (red, disk-shaped patch) Photosensitivity Oral Ulcers Arthritis Kidney, Neuro or Blood Disorder
(need >4 or biopsy with positive ANA/Anti-DNA)
Diagnostic Criteria for SLE
> 4 signs/symptoms
OR
Biopsy-proven nephritis with positive ANA/Anti-DNA
Widespread muscular pain; seen in >30% of SLE patients; focuses on major joints (knees, elbows, neck, etc.)
Fibromyalgia
CNS manifestations of SLE
AMS Anxiety/Psychosis Depression CVA Seizures Polyneuropathy Guillian Barre Myasthenia Gravis
MAJOR risk of early SLE disease, especially in young onset SLE; may be due to thrombosis, dissection, atherosclerosis and fibromuscular dysplasia; 90% are ischemic
CVA
90% of SLE induces CVAs are (Ischemic/Hemorrhagic)
Ischemic
GI manifestations of SLE
Dysphagia/Odynophagia
GERD (assoc. with Raynauds)
Mesenteric Vasculitis/Ischemia
Hematologic manifestations of SLE
Anemia (Chronic disease, iron def., autoimmune)
Leukopenia (antibody mediated)
ITP
Examples of Thrombocytopenias in SLE
ITP (most common)
Antiphospholipid Antibody Syndrome
TTP
Cause of Thrombocytopenia in SLE; acquired disorder with autoantibodies against phospholipids; detected by presence of “lupus anticoagulant”; paradoxically causes THROMBOSES, abnormal blood flow and pregnancy loss; treat with anticoagulation
Antiphospholipid Antibody Syndrome
Treatment for Antiphospholipid Antibody Syndrome
Anticoagulation
Examples of SLE antibodies associated with Antiphospholipid Antibody Syndrome (3 total)
Anti-cardiolipin
Anti-B2-glycoprotein
Lupus anticoagulant
Pulmonary manifestations of SLE
Restrictive/Interstitial disease
Pleuritis + Effusion
Pulmonary Embolism
Pulmonary HTN and Hemorrhage
Lupus Pneumonitis can look just like Infectious Pneumonia due to fever, cough, alveolar damage and edema (True or False)
True (requires lavage and biopsy to confirm)
Most life-threatening Pulmonary manifestation of SLE
Pulmonary Hemorrhage (hemoptysis in only 50% of patients)
Cardiac manifestations of SLE
Pericarditis
Myocarditis
Libman Sacks (verrucous/marantic) Endocarditis
Fancy names for SLE induced Endocarditis
Libman Sacks
Verrucous
Marantic
Sterile/Non-bacterial
Leading causes of Mortality in SLE
Heart disease
Infection
Malignancy
Treatments for SLE
Sun avoidance
Hydroxychloroquine (antimalarial)
Corticosteroids
Why is the antimalarial Hydroxychloroquine used for SLE
Antagonist activity against TLRs 3, 7, 8 and 9 dec. the activation of the innate immune system (dendritic cells)
Examples of Immunosuppressives used in SLE
Cyclophosphamide Azathioprine Mycophenolate Methotrexate Leflunomide Cyclosporine Belimumab Rituximab Abatacept
(Nephrotic/Nephritic) syndrome is characterized by proteinuria, edema and hyperlipidemia
Nephrotic
(Nephrotic/Nephritic) syndrome is characterized by hematuria, HTN and oliguria
Nephritic
When should you obtain a kidney biopsy in SLE
Inc. serum creatinine (no other cause)
Proteinuria >1g/day
Renal manifestations of SLE
Nephritis
Thombotic Microangiopathy
Tubulo-Interstitial Nephritis (Type 1 RTA)
ANCA overlap with Lupus
Treatments for SLE (besides immunosuppression)
ACEi/ARBs (Renal)
Statins (CAD)
Aspirin and/or Warfarin (APS)
PPI or H2 Blockers (GERD)
Nephrotic/Nephritic syndromes associated with SLE
Membranous
Proliferative Lupus Nephritis
Complement abnormality seen with SLE
Low C3 and C4
Proteins produced in response to an antigen; function as chemical messengers for regulating the innate and adaptive immune systems
Cytokines
Cytokine made by T and NK cells; responsible for activation of macrophages
IFN-y
Cytokine responsible for the inhibition of T cells and differentiation of Treg cells
TGF-b
Cytokine responsible for T cell proliferation
IL-2
Cytokine responsible for the stimulation of acute inflammation
IL-17
Cytokines responsible for stimulating production of IgE and eosinophils
IL-4 and 5
Cytokine responsible for the recruitment of neutrophils
IL-8
Cytokine responsible for the stimulation of Bone marrow stem cells
IL-3
Hypersensitivity Reaction: characterized by IMMEDIATE hypersensitivity and allergic response via mast cells, IgE and eosinophils
Type 1
Hypersensitivity Reaction; characterized by IgM/G antibodies against CELL SURFACE or matrix antigens; opsonization and phagocytosis of cells
Type 2
Hypersensitivity Reaction: characterized by Immune COMPLEXES of circulating antigens depositing in vascular BASEMENT MEMBRANES; complement-mediated recruitment of leukocytes and resultant inflammation
Type 3
Hypersensitivity Reaction: characterized by T-cell recruitment and direct target cell lysis; DELAYED onset
Type 4
SLE is an example of Type (1/2/3/4) Hypersensitivity
3 (antibody complex mediated)
Type 1 Diabetes Mellitus is an example of Type (1/2/3/4) Hypersensitivity
4 (T-cell mediated)
Examples of Type 4 Hypersensitivity Reactions
Multiple Sclerosis Rheumatoid Arthritis Type 1 DM Crohn's Contact sensitivity (poison ivy)
(Positive/Negative) Thymic selection is when T-cells that are at least somewhat reactive to MHC presentation
Positive
(Positive/Negative) Thymic selection is when any T cells that react to self-antigens with high affinity are killed; prevents possible auto-reactive T cells
Negative
MHC (1/2) present proteins from intracellular pathogens to CD8 T cells
MHC 1
MHC (1/2) present proteins from extracellular pathogens to CD4 T cells
MHC 2
Treg cells need the transcription factor _________ for proper function
FoxP3
How do Treg cells suppress the immune response (3 ways)
Produce inhibitory cytokines
Express CTLA-4 (inhibit T-cell activation)
Express IL-2 receptor (capture IL-2)
The secondary signal (B7/CD28) is located on the APC
B7
The secondary signal (B7/CD28) is located on the T cell
CD28
