SLE is an autoimmune disease in which autoantibodies are produced to components of the cell nucleus, spliceosome, and other cell components that are exposed to the elements of the immune system during apoptosis.
- A patient has fatigue and joint pain and is concerned about the possibility of SLE after reading about this condition on the Internet. After taking a brief history, you decide that further evaluation is appropriate. I addition to the history and physical findings,, which one of the following laboratory findings would most support the diagnosis of SLE?
A. A normal C-reactive protein level
B. An erythrocyte sedimentation rate of 44 mm/hr
D. A positive antimicrosomal antibody test
D. A positive test for antiphospholipid antibodies
E. A positive test for rheumatoid factor
Answer is D – you need a positive test for ANA and antiphospholipid antibodies
2. For several years a hypersensitive 65-year-old female has been treated with hydrochlorothazide, 25 mg/day; atenolol, 100 mg/day, and hydralazine, 50 mg 4 times/day. Her blood pressure has been well controlled on this regimen. Over the past two months she has experienced malaise, along with diffuse joint pains that involve symmetric sites in the fingers, hands, elbows, and knees. A pleural friction rub is noted on examination. Laboratory testing shows that the patient has mild anemia and leukopenia, with a negative rheumatoid factor and a positive antinuclear antibody – ANA titer of 1:640. Which one of the following would be the most appropriate INITIAL step?
A. Replace hydrochlorothiazide with furosemide
B. Discontinue hydralazine
C. Start prednisone, 40 mg/day orally
D. Start hydroxychloroquine, 400 mg/day
Ans – B B/C autoimmune induced med
3. What is the most specific indicator of Raynaud’s
phenomenon commonly associated with SLE or a related connective tissue disease?
B. Diffuse myalgias and arthralgias
C. Dilated capillary loops on capillary microscopy
D. History of first-degree relative with SLE
E. Onset of severe fatigue in the last 2 months
Ans – C
Malar rash – butterfly rash on face
Discoid rash – red patches with scales and alopecia
Arthritis – 90%
Hematologic abnormalities – anemia, reduced platelets
Evidence has accumulated to show that the Toll-like receptors (TLRs) of the innate immune system recognize self-antigens, especially _______, that are liberated during cell apoptosis.
The concordance rate for susceptibility to lupus is much higher between
______ than _______
A. monozygotic than dizygotic twins
B. dizygotic than monozygotic twins
In phase 1, antigen is presented by the ____ stystem
In phase 2, variants of the protein __________ non-receptor type 22 (PTPN 22) gene have been associated with SLE.
A. tyrosine phosphatase
B. Interferon 1
The protein encoded by this gene removes _______ from proteins that have been inserted by tyrosine kinases. Phosphorylation of selected tyrosine residues in proteins is often a means by which to send a growth signal. PTPN22 has also been implicated in the pathogenesis of rheumatoid arthritis, another autoimmune disease.
A. Carboxyl groups
B. Phosphate groups
In phase 3, autoantibodies and immune complexes form, but do not cause overt clinical manifestations because it takes time for the effects to be felt. During phase 4, ________ activation and other inflammatory reactions attack tissues to which autoantibodies and immune complexes have attached.
Ultraviolet light can trigger lupus flares causing damage to DNA and formation of _______ in skin cells. This damage induces apoptosis and concentrates nucleic acid and _____ in cell membrane blebs.
A. immune complexes, dsDNA
B. thymine dimers, histones
The autoantibodies formed in SLE are directed against DNA- NUCLEOSOMES and RNA-protein complexes SPLICEOSOMES
During apoptosis,_________ become localized on the surface of cells undergoing programmed destruction. Later, antibodies to _______often develop. This class of antibodies represents those that are tested in the well-known antinuclear antibody (ANA) test. While this classical antibody is found in approximately 95% of patients with lupus, ANA is also found in numerous other autoimmune disorders, thus it is not specific for SLE.
A. Nucelosomes, dsDNA
B. PAMPs, RNA
Another autoantibody highly specific for SLE is the anti-Smith (anti-Sm) antibody. Anti-Smith antibodies are directed against small nuclear _______ with protein, and are found in 20%-30% of patients.
A. RNAs complexes
B. DNA complexes
Autoantibodies against proteins associated with the Ro particle have been found in infants with congenital heart block. These proteins are associated with ____.
Antibodies coat platelets and erythrocytes and can cause immune-mediated thrombocytopenia and _______.
Antibodies against phospholipids and β2 –glycoprotein I, which has an important role in blood coagulation, increase the risk of ______.
It is noteworthy, that there are autoantibodies in some patients with lupus that bind to the _________ receptor (an excitatory receptor), which causes death of cells in the hippocampus. This may be a factor in the CNS manifestations of lupus.
A. gaba (N-methyl-D-aspartate)
B. glutamate (N-methyl-D-aspartate)
T or F:
Large and small immune complexes are believed to play a role in the pathogenesis of SLE.
F. Large immune complexes are efficiently removed from circulation by monocytes and macrophages.
There is abundant evidence that immune complexes that fix ________are the primary source of tissue damage in SLE.
It has recently been demonstrated that regulatory regions controlling the expression of CD40L on T cells on the inactivated X-chromosome of women with SLE is ____________(thereby activated), causing increased expression of CD40L.
Lack of CD40L prevents isotype switching. In lupus the exaggerated expression of CD40L augments T-cell signaling of B-cells, ramping up production of immunoglobulins.
Experimental studies have revealed that ______ prolongs the life of autoreactive B- and T-cells, creating an environment that favors development of autoimmunity
Specifically, estradiol upregulates the expression of CD40L on T cells.
Another factor in the development of autoimmunity is inadequate down-regulation of T cells by Tregs (suppressor cells) in lupus. This is believed to be the result of decreased production of ____ by SLE T cells.
DCs secrete ___________, two pro-inflammatory cytokines that further augment the immune response to apoptotic self-antigens. This regulation of and by DCs is deranged in patients with SLE.
A. IL-6 and IFN-α
B. IL-2 and IFN-α
Normally, the _____ fragment of the classical complement pathway functions as an opsonin to help clear apoptotic cells and immune complexes as part of a “waste disposal” function. In SLE, deficiency of ___ has been shown to occur, further compromising removal of potential self-antigen.
Furthermore, there is now evidence that C1q normally delivers inhibitory signals to DCs so that deficiency of C1q has the additional adverse effect of increasing autoantibody production and activating T-cells. Thus, C1q turns out to be a potent modulator of T cell activity.
Photosensitivity is well-known in patients with lupus and avoidance of ____ in sunlight and fluoresecent lights is important.
RENAL SYSTEM SLE
Deposition of immune complexes in the mesangium is associated with ________ and mild proteinuria.
A. microscopic hematuria
b. macroscopic hematuria
Subepithelial deposition of immune complexes adjacent to podocytes and along the glomerular basement membrane produce membranous nephritis and nephrotic-type proteinuria (>3.5 g/d). Subendothelial deposition of immune complexes produces nephritic features with proliferative and exudative inflammation, manifested as hematuria, mild proteinuria, and a decreased GFR.
The World Health Organization (WHO) classification of lupus nephritis created six classes of renal lesions in SLE. Classes I and II involve mesangial deposition, class III is focal glomerulonephritis (GN), class IV is diffuse GN nephrtis, class V is membranous lupus nephritis, and class VI is advanced sclerotic lupus nephritis. Type IV SLE (approximately 45%) is the most common, with types III (approximately 25%) and V (approximately 15%) following behind in frequency.
Anti-DNA antibodies and the C3 complement component are the best laboratory tests to monitor disease activity. Serum creatinine is only useful after renal insufficiency has developed.