Elevated serum level of soluble CD23 precedes development of B-non-Hodgkin's lymphoma in SIV-infected Rhesus monkeys.
Patients with HIV infection are at high risk for the development of high-grade B-non-Hodgkin's lymphoma (B-NHL). The aim of this study was identification of a predictive diagnostic marker for HIV-associated B-cell lymphomas, using simian-immunodeficiency-virus (SIV)-infected Rhesus monkeys as a well-established in vivo model of HIV-associated lymphomagenesis. We infected 26 monkeys (Macaca mulatta) with SIVmax and measured serum levels of sCD23 longitudinally until necropsy. Of the 26 monkeys, 9 developed high-grade B-NHL, which was preceded by lymphadenopathy (NHL+/LA+) (group 1). Among the 17 animals that remained without clinical evidence of lymphoma during the observation period, 8 developed LA (group 2) and 9 were NHL- and LA-negative (NHL-/LA-) (group 3). Elevation of sCD23 serum levels preceded B-cell lymphoma development, with a median of 44 U/ml in group 1 vs. 7 U/ml and 8 U/ml in groups 2 and 3 respectively, 32 weeks after infection. Differences in the serum level of sCD23 between group 1 vs. groups 2 and 3 became statistically significant 32 to 56 weeks after infection. At necropsy, serum levels of sCD23 were significantly higher in group 1 than in group 2 or group 3; 6/6 samples of SIV-associated B-NHL were positive for gene transcription of CD23 and its receptor CD21 as assessed by RT-PCR. The data point to a potential role of sCD23 as a predictive marker for the development of HIV-associated B-NHL. Moreover, the in vivo model of SIV-infected monkeys suggests the possibility of exactly analyzing the pathobiological role of sCD23 in the lymphomagenesis of SIV-associated B-NHL.
German Primate Center, Department for Virology and Immunology, Göttingen. studyce@med.uni-goettingen.de
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H
Hannig
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Buske
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Mätz-Rensing
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Hunsmann
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Hiddemann
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Bodemer
D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008206:Lymphatic Diseases / Q000209:etiology; D016393:Lymphoma, B-Cell / Q000097:blood / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D008253:Macaca mulatta; D008297:Male; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D017455:Receptors, IgE / Q000096:biosynthesis / Q000097:blood*; D012680:Sensitivity and Specificity; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000150:complications* / Q000276:immunology; D015302:Simian Immunodeficiency Virus; D013997:Time Factors; D014158:Transcription, Genetic
D014408:Biomarkers, Tumor; D017455:Receptors, IgE