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The association between obesity and oligoclonal band formation in multiple sclerosis patients
Obesity Research & Clinical Practice (2015) 9, 533—535
RESEARCH LETTER The association between obesity and oligoclonal band formation in multiple sclerosis patients
KEYWORDS Body-mass index; Obesity; Oligoclonal band; Multiple sclerosis
Summary Since some neurological disorders present with increased body-mass index (BMI) and cerebrospinal fluid (CSF) oligoclonal bands (OCB), obesity-induced inflammation has been previously speculated in formation of OCB. We investigated the association between BMI, OCB formation and clinical features of MS in 120 patients with relapsing remitting multiple sclerosis (RRMS), a disease with high OCB positivity incidence. Thirty RRMS patients had BMI ≥ 30 and 100 patients displayed CSF OCB. OCB positive and negative patients had comparable BMI and weight values. Disease duration, annual attack number and EDSS were not correlated with BMI and body weight. Patients with normal and high BMI did not significantly differ by means of OCB positivity, gender, annual attack number, disease duration and EDSS scores. Our results argue against a possible role of obesity in OCB formation. Moreover, obesity does not appear to influence disability and clinical progression of MS patients. © 2015 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.
Idiopathic intracranial hypertension (IIH), a neurological disease characterised with increased intracranial pressure in the absence of a structural lesion or any other identifiable reason, and rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome patients often present with increased body-mass index (BMI), systemic inflammation findings and oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) [1—3]. OCBs that are predominantly detected in CSF practically represent IgG exclusively produced in the intrathecal compartment and suggest a chronic inflammatory state in the central nervous system [4]. Since adipose tissue releases cytokines and might be a potential trigger of inflammation, obesity-induced inflammation has been speculated to be a potential cause of OCB formation in IIH and ROHHAD syndromes. Based on this idea, we investigated the role of obesity in OCB formation in multiple sclerosis (MS), another neurological disease with a high incidence of CSF OCBs.
For this purpose, 120 consecutive relapsing remitting multiple sclerosis (RRMS) patients were recruited. OCBs were detected in sera and CSF by isoelectric focusing and immunoblotting, which produce one of five internationally standardised distinct patterns [4]. Pattern 1 indicates that CSF and serum do not contain OCBs. Pattern 2 discloses the presence of OCBs only in CSF. Identical bands in serum and CSF plus additional bands in CSF is recognised as pattern 3. Pattern 4 represents identical bands found in serum and CSF indicating systemic immune activation. Pattern 5 represents monoclonal bands and is associated with systemic paraproteinemia. Pattern 1 was defined as OCB negative and patterns 2 and 3, which indicate intrathecal IgG production and are characteristic for MS were accepted as OCB positive. BMI ≥ 30 kg/m2 was assigned to obesity. The associations between age, gender, BMI, body weight values, OCB patterns and clinical features [disease duration, expanded disability status scale (EDSS),
http://dx.doi.org/10.1016/j.orcp.2015.07.001 1871-403X/© 2015 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.
534 Table 1
Research Letter Comparison of MS patients with and without obesity (BMI of 30 or greater).
CSF OCB positive Age (mean ± SD) Gender (women/men) EDSS (mean ± SD) Annual attack number (mean ± SD) Disease duration (years) (mean ± SD)
BMI < 30 (n = 90)
BMI ≥ 30 (n = 30)
p value
78/90 (86.7%) 34.2 ± 9.1 (21—60) 54/36 2.5 ± 1.1 (1.0—5.0) 2.2 ± 1.3 (0—6) 6.3 ± 5.6 (1—22)
22/30 (73.3%) 44.5 ± 7.4 (31—59) 18/12 2.5 ± 0.9 (1.0—5.0) 2.3 ± 1.1 (1—5) 5.1 ± 5.1 (1—14)
0.089* <0.001** 1.000* 0.486† 0.446** 0.239**
BMI, body-mass index; CSF, cerebrospinal fluid; OCB, oligoclonal bands; EDSS, expanded disability status scale; SD, standard deviation. * Chi-square test. ** Student’s t-test. † Mann—Whitney U.
annual attack number] of RRMS were investigated by chi-square test, Pearson test and Student’s ttest, as required. The study was approved by the local ethics committee. Seventy-two patients were female. The mean age (±standard deviation, range) was 36.8 ± 9.7 (21—60). Mean disease duration was 18.2 ± 10.1 years (1—22), mean EDSS was 2.5 ± 1.1 (1.0—5.0), mean BMI was 25.7 ± 4.6 (17.6—37.8) and mean body weight was 71.6 ± 14.7 kg (range: 49—116). Thirty patients had BMI ≥ 30 kg/m2 . One hundred patients were OCB positive (pattern 2 in 88, pattern 3 in 12) and 20 were OCB negative. OCB positive and negative patients had comparable BMI (26.9 ± 4.9 vs 25.5 ± 4.6) and body weight (76.7 ± 16.3 kg vs 70.5 ± 14.3 kg) values (p > 0.05 for both). Disease duration, annual attack number and EDSS were not correlated with BMI and body weight (p > 0.05 for all). The patients with increased BMI (≥30) showed trends towards exhibiting reduced OCB positivity rates (22/30, 73.3%) than patients with normal BMI (78/90, 86.7%, p = 0.089). Patients with normal and increased BMI did not significantly differ by means of gender, annual attack number, disease duration and EDSS scores (p > 0.05) (Table 1). This is the first study to investigate the role of obesity in OCB formation in MS patients and generally argues against a participating role of obesity in OCB formation. Therefore, OCB formation observed in IIH and ROHHAD is probably not a direct consequence of obesity and it is more likely that an immunity directed against specific structures of diencephalon is causing obesity, OCB formation and neurological symptoms in these syndromes. There are only a few previous studies associated with obesity and MS. In a recent study, levels of chemerin, a novel chemoattractant molecule
produced by adipose tissue, were found higher in overweight MS subjects with CSF OCBs [5]. Additionally, some other studies have observed an association between BMI in childhood or adolescence and MS risk, whereas obesity in adulthood was not associated with increased MS risk [6—8]. Notably, in our study obesity did not appear to influence disability and clinical progression of RRMS. Among previous studies focused on BMI and disability association in MS, some have findings consistent with ours, whereas others do not [9—11]. Additional studies are required to elucidate the mechanisms by which obesity and adipose tissue could contribute to the clinical progression and disability in MS patients.
Conflict of interest The authors have no conflict of interest to disclose.
References [1] Dhungana S, Sharrack B, Woodroofe N. Cytokines and chemokines in idiopathic intracranial hypertension. Headache 2009;49:282—5. [2] Sartori S, Priante E, Pettenazzo A, Marson P, Suppiej A, Benini F, et al. Intrathecal synthesis of oligoclonal bands in rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome: new evidence supporting immunological pathogenesis. J Child Neurol 2014;29:421—5. [3] Altıokka-Uzun G, Tüzün E, Ekizo˘ glu E, Ulusoy C, Yentür S, Kürtüncü M, et al. Oligoclonal bands and increased cytokine levels in idiopathic intracranial hypertension. Cephalalgia 2015;(February), pii:0333102415570762 [Epub ahead of print]. [4] Petzold A. Intrathecal oligoclonal IgG synthesis in multiple sclerosis. J Neuroimmunol 2013;262:1—10.
The association between obesity and oligoclonal band formation in multiple sclerosis patients [5] Tomalka-Kochanowska J, Baranowska B, Wolinska-Witort E, Uchman D, Litwiniuk A, Martynska L, et al. Plasma chemerin levels in patients with multiple sclerosis. Neuro Endocrinol Lett 2014;35:218—23. [6] Langer-Gould A, Brara SM, Beaber BE, Koebnick C. Childhood obesity and risk of pediatric multiple sclerosis and clinically isolated syndrome. Neurology 2013;80: 548—52. [7] Munger KL, Chitnis T, Ascherio A. Body size and risk of MS in two cohorts of US women. Neurology 2009;73: 1543—50. [8] Hedstrom AK, Olsson T, Alfredsson L. High body mass index before age 20 is associated with increased risk for multiple sclerosis in both men and women. Mult Scler 2012;18:1334—6. [9] Slawta JN, Wilcox AR, McCubbin JA, Nalle DJ, Fox SD, Anderson G. Health behaviors, body composition, and coronary heart disease risk in women with multiple sclerosis. Arch Phys Med Rehabil 2003;84:1823—30. [10] Tettey P, Simpson Jr S, Taylor B, Blizzard L, Ponsonby AL, Dwyer T, et al. Adverse lipid profile is not associated with relapse risk in MS: results from an observational cohort study. J Neurol Sci 2014;340(1/2):230—2. [11] Marrie R, Horwitz R, Cutter G, Tyry T, Campagnolo D, Vollmer T. High frequency of adverse health behaviors in multiple sclerosis. Mult Scler 2009;15:105—13.
535
Arzu C ¸ oban ∗ Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey Denef C ¸ evik Selen Özyurt Mehmet Gencer Department of Neurology, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey Erdem Tüzün Department of Neuroscience, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey Recai Türko˘ glu Department of Neurology, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey ∗ Corresponding author. Tel.: +90 2124142000; fax: +90 2125334393. E-mail address: [email protected] (A. C ¸ oban)
Available online at www.sciencedirect.com
ScienceDirect
10 June 2015
RESEARCH LETTER The association between obesity and oligoclonal band formation in multiple sclerosis patients
KEYWORDS Body-mass index; Obesity; Oligoclonal band; Multiple sclerosis
Summary Since some neurological disorders present with increased body-mass index (BMI) and cerebrospinal fluid (CSF) oligoclonal bands (OCB), obesity-induced inflammation has been previously speculated in formation of OCB. We investigated the association between BMI, OCB formation and clinical features of MS in 120 patients with relapsing remitting multiple sclerosis (RRMS), a disease with high OCB positivity incidence. Thirty RRMS patients had BMI ≥ 30 and 100 patients displayed CSF OCB. OCB positive and negative patients had comparable BMI and weight values. Disease duration, annual attack number and EDSS were not correlated with BMI and body weight. Patients with normal and high BMI did not significantly differ by means of OCB positivity, gender, annual attack number, disease duration and EDSS scores. Our results argue against a possible role of obesity in OCB formation. Moreover, obesity does not appear to influence disability and clinical progression of MS patients. © 2015 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.
Idiopathic intracranial hypertension (IIH), a neurological disease characterised with increased intracranial pressure in the absence of a structural lesion or any other identifiable reason, and rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome patients often present with increased body-mass index (BMI), systemic inflammation findings and oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) [1—3]. OCBs that are predominantly detected in CSF practically represent IgG exclusively produced in the intrathecal compartment and suggest a chronic inflammatory state in the central nervous system [4]. Since adipose tissue releases cytokines and might be a potential trigger of inflammation, obesity-induced inflammation has been speculated to be a potential cause of OCB formation in IIH and ROHHAD syndromes. Based on this idea, we investigated the role of obesity in OCB formation in multiple sclerosis (MS), another neurological disease with a high incidence of CSF OCBs.
For this purpose, 120 consecutive relapsing remitting multiple sclerosis (RRMS) patients were recruited. OCBs were detected in sera and CSF by isoelectric focusing and immunoblotting, which produce one of five internationally standardised distinct patterns [4]. Pattern 1 indicates that CSF and serum do not contain OCBs. Pattern 2 discloses the presence of OCBs only in CSF. Identical bands in serum and CSF plus additional bands in CSF is recognised as pattern 3. Pattern 4 represents identical bands found in serum and CSF indicating systemic immune activation. Pattern 5 represents monoclonal bands and is associated with systemic paraproteinemia. Pattern 1 was defined as OCB negative and patterns 2 and 3, which indicate intrathecal IgG production and are characteristic for MS were accepted as OCB positive. BMI ≥ 30 kg/m2 was assigned to obesity. The associations between age, gender, BMI, body weight values, OCB patterns and clinical features [disease duration, expanded disability status scale (EDSS),
http://dx.doi.org/10.1016/j.orcp.2015.07.001 1871-403X/© 2015 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.
534 Table 1
Research Letter Comparison of MS patients with and without obesity (BMI of 30 or greater).
CSF OCB positive Age (mean ± SD) Gender (women/men) EDSS (mean ± SD) Annual attack number (mean ± SD) Disease duration (years) (mean ± SD)
BMI < 30 (n = 90)
BMI ≥ 30 (n = 30)
p value
78/90 (86.7%) 34.2 ± 9.1 (21—60) 54/36 2.5 ± 1.1 (1.0—5.0) 2.2 ± 1.3 (0—6) 6.3 ± 5.6 (1—22)
22/30 (73.3%) 44.5 ± 7.4 (31—59) 18/12 2.5 ± 0.9 (1.0—5.0) 2.3 ± 1.1 (1—5) 5.1 ± 5.1 (1—14)
0.089* <0.001** 1.000* 0.486† 0.446** 0.239**
BMI, body-mass index; CSF, cerebrospinal fluid; OCB, oligoclonal bands; EDSS, expanded disability status scale; SD, standard deviation. * Chi-square test. ** Student’s t-test. † Mann—Whitney U.
annual attack number] of RRMS were investigated by chi-square test, Pearson test and Student’s ttest, as required. The study was approved by the local ethics committee. Seventy-two patients were female. The mean age (±standard deviation, range) was 36.8 ± 9.7 (21—60). Mean disease duration was 18.2 ± 10.1 years (1—22), mean EDSS was 2.5 ± 1.1 (1.0—5.0), mean BMI was 25.7 ± 4.6 (17.6—37.8) and mean body weight was 71.6 ± 14.7 kg (range: 49—116). Thirty patients had BMI ≥ 30 kg/m2 . One hundred patients were OCB positive (pattern 2 in 88, pattern 3 in 12) and 20 were OCB negative. OCB positive and negative patients had comparable BMI (26.9 ± 4.9 vs 25.5 ± 4.6) and body weight (76.7 ± 16.3 kg vs 70.5 ± 14.3 kg) values (p > 0.05 for both). Disease duration, annual attack number and EDSS were not correlated with BMI and body weight (p > 0.05 for all). The patients with increased BMI (≥30) showed trends towards exhibiting reduced OCB positivity rates (22/30, 73.3%) than patients with normal BMI (78/90, 86.7%, p = 0.089). Patients with normal and increased BMI did not significantly differ by means of gender, annual attack number, disease duration and EDSS scores (p > 0.05) (Table 1). This is the first study to investigate the role of obesity in OCB formation in MS patients and generally argues against a participating role of obesity in OCB formation. Therefore, OCB formation observed in IIH and ROHHAD is probably not a direct consequence of obesity and it is more likely that an immunity directed against specific structures of diencephalon is causing obesity, OCB formation and neurological symptoms in these syndromes. There are only a few previous studies associated with obesity and MS. In a recent study, levels of chemerin, a novel chemoattractant molecule
produced by adipose tissue, were found higher in overweight MS subjects with CSF OCBs [5]. Additionally, some other studies have observed an association between BMI in childhood or adolescence and MS risk, whereas obesity in adulthood was not associated with increased MS risk [6—8]. Notably, in our study obesity did not appear to influence disability and clinical progression of RRMS. Among previous studies focused on BMI and disability association in MS, some have findings consistent with ours, whereas others do not [9—11]. Additional studies are required to elucidate the mechanisms by which obesity and adipose tissue could contribute to the clinical progression and disability in MS patients.
Conflict of interest The authors have no conflict of interest to disclose.
References [1] Dhungana S, Sharrack B, Woodroofe N. Cytokines and chemokines in idiopathic intracranial hypertension. Headache 2009;49:282—5. [2] Sartori S, Priante E, Pettenazzo A, Marson P, Suppiej A, Benini F, et al. Intrathecal synthesis of oligoclonal bands in rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome: new evidence supporting immunological pathogenesis. J Child Neurol 2014;29:421—5. [3] Altıokka-Uzun G, Tüzün E, Ekizo˘ glu E, Ulusoy C, Yentür S, Kürtüncü M, et al. Oligoclonal bands and increased cytokine levels in idiopathic intracranial hypertension. Cephalalgia 2015;(February), pii:0333102415570762 [Epub ahead of print]. [4] Petzold A. Intrathecal oligoclonal IgG synthesis in multiple sclerosis. J Neuroimmunol 2013;262:1—10.
The association between obesity and oligoclonal band formation in multiple sclerosis patients [5] Tomalka-Kochanowska J, Baranowska B, Wolinska-Witort E, Uchman D, Litwiniuk A, Martynska L, et al. Plasma chemerin levels in patients with multiple sclerosis. Neuro Endocrinol Lett 2014;35:218—23. [6] Langer-Gould A, Brara SM, Beaber BE, Koebnick C. Childhood obesity and risk of pediatric multiple sclerosis and clinically isolated syndrome. Neurology 2013;80: 548—52. [7] Munger KL, Chitnis T, Ascherio A. Body size and risk of MS in two cohorts of US women. Neurology 2009;73: 1543—50. [8] Hedstrom AK, Olsson T, Alfredsson L. High body mass index before age 20 is associated with increased risk for multiple sclerosis in both men and women. Mult Scler 2012;18:1334—6. [9] Slawta JN, Wilcox AR, McCubbin JA, Nalle DJ, Fox SD, Anderson G. Health behaviors, body composition, and coronary heart disease risk in women with multiple sclerosis. Arch Phys Med Rehabil 2003;84:1823—30. [10] Tettey P, Simpson Jr S, Taylor B, Blizzard L, Ponsonby AL, Dwyer T, et al. Adverse lipid profile is not associated with relapse risk in MS: results from an observational cohort study. J Neurol Sci 2014;340(1/2):230—2. [11] Marrie R, Horwitz R, Cutter G, Tyry T, Campagnolo D, Vollmer T. High frequency of adverse health behaviors in multiple sclerosis. Mult Scler 2009;15:105—13.
535
Arzu C ¸ oban ∗ Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey Denef C ¸ evik Selen Özyurt Mehmet Gencer Department of Neurology, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey Erdem Tüzün Department of Neuroscience, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey Recai Türko˘ glu Department of Neurology, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey ∗ Corresponding author. Tel.: +90 2124142000; fax: +90 2125334393. E-mail address: [email protected] (A. C ¸ oban)
Available online at www.sciencedirect.com
ScienceDirect
10 June 2015