paganini
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A 27 year old woman comes to the physician because of pain on her hands, hematuria and RBC casts. Two moths ago she presented a rash on the cheeks. This woman has a disorder characterized by the production of autoantibodies against:
A. Several tRNAs
B. Components of the transcriptional machinery
C. The small 5S rRNAs
D. Components of the splicing machinery
E. Components of the tRNA modifying enzymes
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| an
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B.components of transcriptional machinery.....( SLE has autoantibodies against RNA polymerase I amongst others)...
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| paganini
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Correct answer is D. Components of the splicing machinery. In other words small nuclear ribonucleoprotein particles (snRNPD, or "snurps"). The snRNPs facilitates the splicing of exon segments by forming base pairs with the consensus sequences at each end of intron.
This patient has Systemic lupus erythematosus. Patients with SLE usually have antibodies to many autoantigens (DNA, histones [most commonly drug induced], ribosomes, snRNP, scRNP). The commonest autoantibody, wich is found in the serum of 60% of all SLE patients, is to double-stranded DNA. Other antibodies very commonly found are to small ribonucleoproteins. Antibodies to blood cells, such as platelets and red blood cells, as well as to the phospholipid complex that is formed by the activation of the proteins of the clotting system (antiphospholipid antibodies), are common but less frequent. Most patients have a range of these autoantibodies. The immune complexes in SLE are small and tend to be trapped or formed inside tissues, primarily in the kidney and, to a smaller extend, in the synovial tissues of joints. For this reason, glomerulonephritis and arthritis are two of the most frequently encountered symptoms of SLE.
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thks paganini for correct answer...
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| mixo
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thx
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| mitali
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this seems to me to be a 3 step Q. is this a real Q someone encountered? step 1 is to diagnose that it is SLE. step 2 is to find out that antibodies in SLE . and step 3, the crucial bit which will give you that amazing score - is to apply this info to molecular biology & figure out what autoantibodies do...now that's tough! reading only the Q, I thought the autoAb have to be against dsDNA. but answers provided also have a logic. I would have thought that Ab should be restricted to 3 in the case of SLE. ANA - highly sensitive ( negative test rules out - SnOUT); dsDNA found in 75% and about 95% specific (my number 1 bet) and finally Smith antibodies - which although found in only 25% are said to be 100% specific. why would someone bother about other autoab? okay, both topoisomerases I (involved in transcription) and snRNP (the guys that clear up the useless bits - introns- from the DNA sequence & join - 'splice'- the useful bits towards forming the mRNA ,could be attacked by autoantibodies as well. so, now invlovement in the transcription & splicing process can also be options. topoI ab are found in some 20% people while snRNP ab are said to be present in pt with mixed connective tissue disease. there is no clue to say this lady has MCTD. it seems to be a simple clear case of SLE with (type 3 HS) immune complexes hitting end organs like kidneys & causing problems. good clinical explanation about the symptoms, paganini. can you explain why the answer u've stated is correct...i am confused....
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| paganini
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Sorry for the delay. I wasn't active in this forum since october 05. So mitali i hope you could read this. Anti-Smith(anti-Sm) is a ribonucleoprotein and is specific for SLE. None of the other choices are correct. As a group, the self-directed immunoglobulins in SLE are referred to as anti-nuclear antibodies (ANA), noted in greater than 95% of SLE cases. Major subtypes include anti-double stranded DNA antibody (directed towards ds DNA in patient cells, with their subsequent destruction); anti-Smith (directed against core proteins in the small nuclear ribosomal complex [snRNP]); anti-histone antibodies, and anti-ribonucleoprotein antibodies (U1RNP). Although these and other antibodies can be seen in other autoimmune disorders (such as systemic sclerosis and Sjögren's syndrome), the combination of the proper clinical features with the presence of anti-ds DNA and anti-Smith antibody is considered virtually diagnostic of SLE.
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