As we noted in our first article on lymphoma, there isn't any quick and simple test to diagnose or predict which PHAs will develop this cancer. Nor are there any symptoms that specifically occur from having lymphoma. To try to remedy the situation, researchers in Italy have been monitoring levels of the a protein called soluble CD23 (sCD23) in the blood and fluid surrounding the brain — cerebrospinal fluid (CSF). They have found higher-than-normal levels of sCD23 in the CSF of PHAs who have brain lymphoma.
Researchers enrolled 36 HIV positive subjects who were diagnosed with non-Hodgkin's lymphoma. Samples of blood and CSF were collected for analysis. For comparison, similar fluids were collected from other PHAs who either had the brain infection toxo (toxoplasmosis), PML (progressive multifocal leukoencephalopathy) or dementia. Samples were also collected from symptom-free HIV positive people as well as from healthy HIV negative people. Measurement of sCD23 was done using a test kit supplied by Pharmingen.
The researchers found that those subjects who had high levels of sCD23 in their CSF were likely to have either brain lymphoma or lymphoma of the brain and elsewhere in their body. Moreover, levels of sCD23 in these subjects' spinal fluid were significantly higher than in samples from subjects with toxo or other brain problems. On average, sCD23 levels in the CSF were as follows:
When technicians measured levels of sCD23 in the blood the results were somewhat different from those seen with the CSF measurements. The subjects with the highest sCD23 levels in the blood had lymphoma outside the brain. Average levels of sCD23 were as follows:
The results from this study suggest that measuring levels of sCD23 in the CSF may be useful in helping to diagnose lymphoma of the brain. Measuring levels of this protein in the blood may not be as useful for confirming the presence of systemic lymphoma.
Most of the lymphomas seen in HIV positive people were once B-cells. Because of HIV's constant stimulation of B-cells, along with weakened immunity, some B-cells in PHAs morph into tumours.
The protein CD23 is found on B-cells as well as on other immune cells such as macrophages. It is possible that overstimulated B-cells, particularly those that are pre-cancerous, produce the high levels of sCD23 that are seen in some PHAs who have lymphoma. Macrophages that are within the brain may also produce this protein when they are activated by the presence of tumours. These two factors may account for the high levels of sCD23 in the CSF of PHAs with lymphoma.
Historically, the only other people who have high levels of sCD23 are those with a certain form of leukemia as well as those with allergies and asthma — other cases where B-cells may be overstimulated. Hopefully further research on sCD23 and lymphoma will be conducted in long-term studies. Results from such studies may help predict which PHAs are at risk of brain and other lymphomas.
REFERENCES
1. Schroeder JR, Saah AJ, Ambinder RF, et al. Serum sCD23 level in patients with AIDS-related non-hodgkin's lymphoma is associated with absence of Epstein-Barr virus in tumor tissue. Clinical Immunology 1999;93(3):239-244.
2. Yawetz S, Cumberland WG, van der Meyden M and Martinez-Maza O. Elevated serum levels of soluble CD23 (sCD23) precede the appearance of acquired immune deficiency syndrome-associated non-Hodgkin's lymphoma. Blood 1995;85(7):1843-1849.
3. Bossolasco S, Nilsson A, de Milito A, et al. Soluble CD23 in cerebrospinal fluid: a marker of AIDS-related non-Hodgkin's lymphoma in the brain. AIDS 2001;15:1109-1113.
4. Kilmon MA, Ghirlando R, Strub M-P, et al. Regulation of IgE production requires oligomerization of CD23. Journal of Immunology 2001;167:3139-3145.
5. Dugas N, Lacroix C, Kilcherr E, et al. Role of CD23 in astrocytes inflammatory reaction during HIV-1 related encephalitis. Cytokine 2001;15(2):96-107.
6.Hannig H, Buske C, Mätz-Rensing K, et al. Elevated serum level of soluble CD23 precedes the development of B-non-Hodgkin's lymphoma in SIV-infected rhesus monkeys. International Journal of Cancer 1998;77:734-740.
7.Miller LS, Atabai K, Nowakowski M, et al. Increased expression of CD23 (Fc receptor II) by peripheral blood monocytes of AIDS patients. AIDS Research and Human Retroviruses 2001;17(5):443-452.
8. Brignone C, Munoz O, Batoz M, et al. Protease produced by activated neutrophils are able to release souble CD23 fragments endowed with proinflammatory effects. Federation of American Societies for Experimental Biology Journal 2001;15(11):2027_9.
9. Garcia DP, Rooney MT, Ahmad E and Davis BH. Diagnostic usefulness of CD23 and FMC-7 antigen expression patterns in B-cell lymphoma classification. American Journal of Clinical Pathology 2001;115(2):258-265 [MedLine].
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Copyright © 2001 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284 http://www.catie.ca.
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