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Advanced Diagnostics Laboratory

Advanced Diagnostics Laboratory. AUTOANTIBODY OF THE MONTH.

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Advanced Diagnostics Laboratory

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  1. Advanced Diagnostics Laboratory AUTOANTIBODY OF THE MONTH Case history: A 24 year old woman is seen by her physician complaining of severe fatigue, joint pain (arthralgia), progressive shortness of breath and a skin “rash” on her legs. The physician discovers that she has an alkaline phosphatase that is elevated 5 times above normal levels. An ANA is performed and is photographed as below. What is the significance of this ANA?

  2. Significance:This serum has anti-Tpr… As illustrated by this serum, we studied the autoantigen targets of 75 sera that had antibodies to the nuclear envelope (NE) as identified by indirect immunofluorescence on HEp-2 cells. Several IIF staining patterns were identified: a smooth membrane pattern characteristic of antibodies to nuclear lamins, a punctate pattern typical of antibodies to the nuclear pore complex, and more complex patterns that included antibodies to nuclear and cytoplasmic organelles. Western immunoblotting of isolated nuclear and NE proteins and immunoprecipitation of radiolabeled recombinant proteins prepared by using the full length cDNAs of the translocated promoter region (Tpr), gp210, and p62 were used to identify specific autoantibody targets. Fifty-two of the 75 (70%) sera bound to Tpr, 25 (33%) bound to lamins A, B, or C, 15 (20%) reacted with gp210 and none reacted with p62. Sixteen (21%) did not react with any of the NE components tested in our assays. The clinical features of 37 patients with anti-NE showed that there were 34 females and 3 males with an age range of 16-88 years (mean 59 yr). The most frequent clinical diagnosis (9/37 = 24%) was autoimmune liver disease (ALD; 2 with primary biliary cirrhosis), followed by 7 (19%) with SLE, 4 (11%) with a motor and/or sensory neuropathy, 3 (8%) with anti-phospholipid syndrome (APS), 2 with SSc, 2 with SjS, and others with a variety of diagnoses. Our studies suggest that Tpr is a common target of human autoantibodies that react with the NE.

  3. Publication Ou Y, Enarson P, Rattner JB, Barr SJ, Fritzler MJ. The nuclear pore complex protein Tpr is a common autoantigen in sera that demonstrate nuclear envelope staining by indirect immunofluorescence. Clin Exp Immunol 136: 379-387, 2004. Reprint available on request: fritzler@ucalgary.ca

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