Neurological Research A Journal of Progress in Neurosurgery, Neurology and Neurosciences
ISSN: 0161-6412 (Print) 1743-1328 (Online) Journal homepage: http://www.tandfonline.com/loi/yner20
Cerebrospinal fluid beta-2-microglobulin in multiple sclerosis and AIDS dementia complex P.B. Carrieri, A. Indaco, A. Maiorino, G.A. Buscaino, A. Ponticiello, A. Liberti & O. Perrella To cite this article: P.B. Carrieri, A. Indaco, A. Maiorino, G.A. Buscaino, A. Ponticiello, A. Liberti & O. Perrella (1992) Cerebrospinal fluid beta-2-microglobulin in multiple sclerosis and AIDS dementia complex, Neurological Research, 14:3, 282-283, DOI: 10.1080/01616412.1992.11740070 To link to this article: http://dx.doi.org/10.1080/01616412.1992.11740070
Published online: 20 Jul 2016.
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Citing articles: 3 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=yner20 Download by: [Australian Catholic University]
Date: 09 August 2017, At: 08:41
Cerebrospinal fluid beta...;2-microglobulin in multiple sclerosis and AIDS dementia complex P.B. Carrieri, A. lndaco, A. Maiorino and G.A. Buscaino Institute of Neurology, 2nd Medical School, University of Naples, Italy
A. Ponticiello, A. Liberti and 0. Perrella
Downloaded by [Australian Catholic University] at 08:41 09 August 2017
D. Cotugno Hospital for Infectious Diseases, Naples, Italy
Cerebrospinal fluid ( CSF) and serum concentrations of beta-2-microglobulin (beta-2-m) were evaluated in 19 patients with clinically definite multiple sclerosis ( MS), in 21 with AIDS dementia complex (ADC), and in 20 subjects with other neurological diseases (OND ). CSF beta-2-m and CSF I serum beta-2-m ratio were significantly higher in the patients with ADC than in the MS and OND patients. The CSF and serum levels of beta-2-m in MS patients were not significantly different from those of OND patients. These findings indicate that CSF beta-2-m and CSF I serum ratio may be a ·useful marker in the diagnosis of ADC. In MS patients the beta-2-r;n CSF determinations are of no value. Keywords : Multiple sclerosis; AIDS dementia complex; beta-2-microglobulin; cerebrospinal fluid INTRODUCTION Beta-2-microglobulin (beta-2-m) is a part of the major histocompatibility complex class I antigen. This small peptide is present in membranes of possibly all nucleated cells, occurring in the highest concentrations on activated T lymphocytes1 . High levels of beta-2-m may reflect an increased turnover of cell membranes . or an activation of cellular immune system 2 . Elevated CSF beta-2-m concentrations have been determined in patients with leukemia or lymphoma with central nervous system (CNS) involvement or in several acute viral CNS infections, as well as in human immunodeficiency virus (HIV) infection 3 - 5 . Multiple sclerosis (MS) is considered . to be an autoimmune disease with an immunological response mediated through T-lymphocytes 6•7 . The patients with MS have signs of intrathecal immunoglobulin synthesis and this could be accompanied by an intrathecal production of beta-2-m. Some reports have recently described increased levels of CSF beta-2-m in MS patients8•9 . In the present study, we determined the CSF and serum beta-2-m levels in subjects with MS, compared with patients with AIDS dementia 1 was assumed to be caused by intrathecal synthesis. Serum creatinine was normal in all patients. Statistics Group comparisons were performed using ANOV A, and Fisher's exact test. Continuous variables were compared using Pearson' s correlation t est. Significance level was established at p < 0.05.
Beta-2-microg/obu/in in CSF: P.B. Carrieri et al. Table 1: CSF and serum beta-2-microglobulin (beta-2-m ) (mg/ 1) and CSF/ serum beta-2-m ratio in patients with multiple sclerosis (MS), AIDS dementia complex (ADC) and other neurological diseases (OND) (m ± SD)
No. MS ADC OND
19 21 20
CSF beta-2-m 1.1 4.8 0.9
± 0.3 ± 2.8**
± 0.3
serum beta-2-m
CSF/ serum beta-2-m ratio
1.7 ± 0.5 3.2 ± 1.1** 1.7 ± 0.4
0.7 0.3 1.7 1.6* 0.5 ± 0.2
± ±
Downloaded by [Australian Catholic University] at 08:41 09 August 2017
• p < 0.01, •• p < 0.005, respect to MS and OND patients.
RESULTS CSF protein, albumin, glucose concentrations and cell count were similar in MS, ADC and OND patients. The CSF and serum levels of beta-2-m in MS patients were not significantly different from those of OND group. The mean CSF and serum levels of beta-2-m were significantly increased in ADC patients with respect to both MS and OND groups (Table 1). Two of 19 MS patients, 19 of 21 ADC patients, and 1 of 20 OND patients had increased CSF beta-2-m levels in excess of mean + 250 of OND patients. One of MS patients, 18 of ADC patients, and 1 of OND patients had abnormal serum beta-2-levels. The beta-2-m ratio in MS patients did not differ significantly from that of OND patients. In the ADC group the CSF I serum beta-2-m ratio was significantly higher with respect to other groups (Table 1). The number of patients with beta-2-m ratio > 1 were the following: MS 1 / 19; ADC 16121 ; OND 0/ 20. Two or more oligoclonal lgG bands in CSF were found _in 18 of 19 MS patients, in 5 of 21 ADC patients, and in 1 of 20 OND patients. Elevated lgG index were found in 14 of 19 MS patients, in 8 of21 ADC patients, and in 1 of 20 OND patients. No correlation was found between CSF and serum beta-2-m, and between CSF beta-2-m concentration and lgG index in each group. ,, DISCUSSION Elevated beta-2-m levels were demonstrated in patients with lymphoproliferative disorders and n_eoplastic CNS rnvolvement ·13 . Our study shows hrgh levels of beta-2-m in both CSF and serum· of ADC patients, in accordance with others 4 •5 . Also ·the CSF / serum beta2-m ratio' appear significantly elevated in ADC patients. The high levels of beta-2-m in CSF during the course of HIV infection seem to be caused by increased intrathecal production. These data suggest a pathogenetic role for local immune response, possibly an activation of the cellular immune reaction in the CNS.
In contrast to previous reports 8 •9, we were unable to confirm a significant increase of beta-2-m in CSF of MS patients. The presence of oligoclonal bands and the elevated lgG index in MS patients do not appear to be reflected in corresponding CSF beta-2-m concentrations or CSF I serum beta-2-m ratio. In conclusion, beta-2-m can be a useful marker in the diagnosis of ADC patients. On the contrary, in MS patients the diagnostic determinations of CSF beta-2-m and CSF I serum beta-2-m ratio are of no value.
ACKNOWLEDGEMENT This study was supported by the Consiglio Nazionale delle Richerche (CNR), research contract no. 9100190 PF 41. REFERENCES
2
3
4
5
6 7
8
9
10
11 12
13
Bernier GM, Fanger MW. Synthesis of beta-2-microglobulin by stimulated lymphocytes. J /mmuno/1972;109: 407-409 Nilsson K, Evrin PE, Berggard I, Ponten j. Involvement of lymphoid and non lymphoid cells in the production of beta-2-microglobulin-a . homologue of the constant domain of lgG. Nature 1973; 244: 44-45 Mavligit GM, Stuckey SE, Cabanillas FF, et a/. Diagnosis of leukaemia or lymphoma in the central nervous system by beta-2-microglobulin determination. N Eng/ J Med 1980; 303: 718-722 Sonnerborg AB, von Stedingk L-V, Hansson L-0, Strannergard 00. Elevated neopterin and beta-2-microglobulin levels in blood and cerebrospinal fluid occur early in HIV-1 infection. AIDS 1989; 3: 277-283 Brew BJ, Shalla RB, Fleisher M, et a/. Cerebrospinal fluid beta-2-microglobulin in patients infected with human immunodeficiency virus. Neurology 1989; 39: 830-834 Colaz J, Steck A, Maretta L. Activated T lymphocytes in patients w ith multiple sclerosis. Neurology 1983; 33: 1371-1373 Hafler DA, Weiner HL. T cells in multiple sclerosis and inflammatory central nervous diseases. lmmunol Rev 1987; 100: 307-332 Bjerrum OW, Lage S, Hansen OE. Measurement of beta-2microglobulin in human cerebrospinal fluid by ELISA technique. Acta Neural Scand 1986; 74: 177-180 Us 0 , Lolli F, Baig S, Link H. Intrathecal synthesis of beta-2-microglobulin in multiple sclerosis and aseptic meningoencephalitis. Acta Neural Scand 1989; 80 : 598- 602 Schumacher GA, Beebe C, Kibler RF, et a/. Problems of ex peri mental trials of therapy 'in multiple sclerosis: report by the panel on the evaluation of experimental trials of the therapy in multiple sclerosis. Ann NY Acad Sci 1965; 122: 552-568 Navia BA, jordan BD, Price RW. The AIDS dementia complex. I. Clinical features. Ann Neuro/ 1986; 19: 51 7-524 Peterslund NA, Black FT, Ceil JP, Mogensen CE. Beta-2microglobulin in the cerebrospinal fluid of patients with infections of the central nervous system. Acta Neural Scand 1989; 80 : 579- 583 Ernerudh J, Olsson T, Berlin C, von Schenk H. Cerebrospinal fluid immunoglobulins and beta-2-microglobulin in lymphoproliferative and other neoplastic disease of the central nervous system. A rch Neuro/1987; 44: 91 5-920
Neurological Research, 1992, Volume 14, june
283
ISSN: 0161-6412 (Print) 1743-1328 (Online) Journal homepage: http://www.tandfonline.com/loi/yner20
Cerebrospinal fluid beta-2-microglobulin in multiple sclerosis and AIDS dementia complex P.B. Carrieri, A. Indaco, A. Maiorino, G.A. Buscaino, A. Ponticiello, A. Liberti & O. Perrella To cite this article: P.B. Carrieri, A. Indaco, A. Maiorino, G.A. Buscaino, A. Ponticiello, A. Liberti & O. Perrella (1992) Cerebrospinal fluid beta-2-microglobulin in multiple sclerosis and AIDS dementia complex, Neurological Research, 14:3, 282-283, DOI: 10.1080/01616412.1992.11740070 To link to this article: http://dx.doi.org/10.1080/01616412.1992.11740070
Published online: 20 Jul 2016.
Submit your article to this journal
View related articles
Citing articles: 3 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=yner20 Download by: [Australian Catholic University]
Date: 09 August 2017, At: 08:41
Cerebrospinal fluid beta...;2-microglobulin in multiple sclerosis and AIDS dementia complex P.B. Carrieri, A. lndaco, A. Maiorino and G.A. Buscaino Institute of Neurology, 2nd Medical School, University of Naples, Italy
A. Ponticiello, A. Liberti and 0. Perrella
Downloaded by [Australian Catholic University] at 08:41 09 August 2017
D. Cotugno Hospital for Infectious Diseases, Naples, Italy
Cerebrospinal fluid ( CSF) and serum concentrations of beta-2-microglobulin (beta-2-m) were evaluated in 19 patients with clinically definite multiple sclerosis ( MS), in 21 with AIDS dementia complex (ADC), and in 20 subjects with other neurological diseases (OND ). CSF beta-2-m and CSF I serum beta-2-m ratio were significantly higher in the patients with ADC than in the MS and OND patients. The CSF and serum levels of beta-2-m in MS patients were not significantly different from those of OND patients. These findings indicate that CSF beta-2-m and CSF I serum ratio may be a ·useful marker in the diagnosis of ADC. In MS patients the beta-2-r;n CSF determinations are of no value. Keywords : Multiple sclerosis; AIDS dementia complex; beta-2-microglobulin; cerebrospinal fluid INTRODUCTION Beta-2-microglobulin (beta-2-m) is a part of the major histocompatibility complex class I antigen. This small peptide is present in membranes of possibly all nucleated cells, occurring in the highest concentrations on activated T lymphocytes1 . High levels of beta-2-m may reflect an increased turnover of cell membranes . or an activation of cellular immune system 2 . Elevated CSF beta-2-m concentrations have been determined in patients with leukemia or lymphoma with central nervous system (CNS) involvement or in several acute viral CNS infections, as well as in human immunodeficiency virus (HIV) infection 3 - 5 . Multiple sclerosis (MS) is considered . to be an autoimmune disease with an immunological response mediated through T-lymphocytes 6•7 . The patients with MS have signs of intrathecal immunoglobulin synthesis and this could be accompanied by an intrathecal production of beta-2-m. Some reports have recently described increased levels of CSF beta-2-m in MS patients8•9 . In the present study, we determined the CSF and serum beta-2-m levels in subjects with MS, compared with patients with AIDS dementia 1 was assumed to be caused by intrathecal synthesis. Serum creatinine was normal in all patients. Statistics Group comparisons were performed using ANOV A, and Fisher's exact test. Continuous variables were compared using Pearson' s correlation t est. Significance level was established at p < 0.05.
Beta-2-microg/obu/in in CSF: P.B. Carrieri et al. Table 1: CSF and serum beta-2-microglobulin (beta-2-m ) (mg/ 1) and CSF/ serum beta-2-m ratio in patients with multiple sclerosis (MS), AIDS dementia complex (ADC) and other neurological diseases (OND) (m ± SD)
No. MS ADC OND
19 21 20
CSF beta-2-m 1.1 4.8 0.9
± 0.3 ± 2.8**
± 0.3
serum beta-2-m
CSF/ serum beta-2-m ratio
1.7 ± 0.5 3.2 ± 1.1** 1.7 ± 0.4
0.7 0.3 1.7 1.6* 0.5 ± 0.2
± ±
Downloaded by [Australian Catholic University] at 08:41 09 August 2017
• p < 0.01, •• p < 0.005, respect to MS and OND patients.
RESULTS CSF protein, albumin, glucose concentrations and cell count were similar in MS, ADC and OND patients. The CSF and serum levels of beta-2-m in MS patients were not significantly different from those of OND group. The mean CSF and serum levels of beta-2-m were significantly increased in ADC patients with respect to both MS and OND groups (Table 1). Two of 19 MS patients, 19 of 21 ADC patients, and 1 of 20 OND patients had increased CSF beta-2-m levels in excess of mean + 250 of OND patients. One of MS patients, 18 of ADC patients, and 1 of OND patients had abnormal serum beta-2-levels. The beta-2-m ratio in MS patients did not differ significantly from that of OND patients. In the ADC group the CSF I serum beta-2-m ratio was significantly higher with respect to other groups (Table 1). The number of patients with beta-2-m ratio > 1 were the following: MS 1 / 19; ADC 16121 ; OND 0/ 20. Two or more oligoclonal lgG bands in CSF were found _in 18 of 19 MS patients, in 5 of 21 ADC patients, and in 1 of 20 OND patients. Elevated lgG index were found in 14 of 19 MS patients, in 8 of21 ADC patients, and in 1 of 20 OND patients. No correlation was found between CSF and serum beta-2-m, and between CSF beta-2-m concentration and lgG index in each group. ,, DISCUSSION Elevated beta-2-m levels were demonstrated in patients with lymphoproliferative disorders and n_eoplastic CNS rnvolvement ·13 . Our study shows hrgh levels of beta-2-m in both CSF and serum· of ADC patients, in accordance with others 4 •5 . Also ·the CSF / serum beta2-m ratio' appear significantly elevated in ADC patients. The high levels of beta-2-m in CSF during the course of HIV infection seem to be caused by increased intrathecal production. These data suggest a pathogenetic role for local immune response, possibly an activation of the cellular immune reaction in the CNS.
In contrast to previous reports 8 •9, we were unable to confirm a significant increase of beta-2-m in CSF of MS patients. The presence of oligoclonal bands and the elevated lgG index in MS patients do not appear to be reflected in corresponding CSF beta-2-m concentrations or CSF I serum beta-2-m ratio. In conclusion, beta-2-m can be a useful marker in the diagnosis of ADC patients. On the contrary, in MS patients the diagnostic determinations of CSF beta-2-m and CSF I serum beta-2-m ratio are of no value.
ACKNOWLEDGEMENT This study was supported by the Consiglio Nazionale delle Richerche (CNR), research contract no. 9100190 PF 41. REFERENCES
2
3
4
5
6 7
8
9
10
11 12
13
Bernier GM, Fanger MW. Synthesis of beta-2-microglobulin by stimulated lymphocytes. J /mmuno/1972;109: 407-409 Nilsson K, Evrin PE, Berggard I, Ponten j. Involvement of lymphoid and non lymphoid cells in the production of beta-2-microglobulin-a . homologue of the constant domain of lgG. Nature 1973; 244: 44-45 Mavligit GM, Stuckey SE, Cabanillas FF, et a/. Diagnosis of leukaemia or lymphoma in the central nervous system by beta-2-microglobulin determination. N Eng/ J Med 1980; 303: 718-722 Sonnerborg AB, von Stedingk L-V, Hansson L-0, Strannergard 00. Elevated neopterin and beta-2-microglobulin levels in blood and cerebrospinal fluid occur early in HIV-1 infection. AIDS 1989; 3: 277-283 Brew BJ, Shalla RB, Fleisher M, et a/. Cerebrospinal fluid beta-2-microglobulin in patients infected with human immunodeficiency virus. Neurology 1989; 39: 830-834 Colaz J, Steck A, Maretta L. Activated T lymphocytes in patients w ith multiple sclerosis. Neurology 1983; 33: 1371-1373 Hafler DA, Weiner HL. T cells in multiple sclerosis and inflammatory central nervous diseases. lmmunol Rev 1987; 100: 307-332 Bjerrum OW, Lage S, Hansen OE. Measurement of beta-2microglobulin in human cerebrospinal fluid by ELISA technique. Acta Neural Scand 1986; 74: 177-180 Us 0 , Lolli F, Baig S, Link H. Intrathecal synthesis of beta-2-microglobulin in multiple sclerosis and aseptic meningoencephalitis. Acta Neural Scand 1989; 80 : 598- 602 Schumacher GA, Beebe C, Kibler RF, et a/. Problems of ex peri mental trials of therapy 'in multiple sclerosis: report by the panel on the evaluation of experimental trials of the therapy in multiple sclerosis. Ann NY Acad Sci 1965; 122: 552-568 Navia BA, jordan BD, Price RW. The AIDS dementia complex. I. Clinical features. Ann Neuro/ 1986; 19: 51 7-524 Peterslund NA, Black FT, Ceil JP, Mogensen CE. Beta-2microglobulin in the cerebrospinal fluid of patients with infections of the central nervous system. Acta Neural Scand 1989; 80 : 579- 583 Ernerudh J, Olsson T, Berlin C, von Schenk H. Cerebrospinal fluid immunoglobulins and beta-2-microglobulin in lymphoproliferative and other neoplastic disease of the central nervous system. A rch Neuro/1987; 44: 91 5-920
Neurological Research, 1992, Volume 14, june
283
