Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: A systematic review and meta-analysis

Intrathecal immunoglobulin-G synthesis is a hallmark of multiple sclerosis (MS), which can be detected by oligoclonal IgG bands (OCB) or by κ-free light chains (κ-FLC) in cerebrospinal fluid. To perform a systematic review and meta-analysis to evaluate whether κ-FLC index has similar diagnostic valu...

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Vydané v:	Multiple sclerosis Ročník 29; číslo 2; s. 169
Hlavní autori:	Hegen, Harald, Walde, Janette, Berek, Klaus, Arrambide, Georgina, Gnanapavan, Sharmilee, Kaplan, Batia, Khalil, Michael, Saadeh, Ruba, Teunissen, Charlotte, Tumani, Hayrettin, Villar, Luisa M, Willrich, Maria Alice V, Zetterberg, Henrik, Deisenhammer, Florian
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	England 01.02.2023
Predmet:	Biomarkers - cerebrospinal fluid Demyelinating Diseases Humans Immunoglobulin G - cerebrospinal fluid Immunoglobulin kappa-Chains - cerebrospinal fluid Multiple Sclerosis - cerebrospinal fluid Multiple Sclerosis - diagnosis Oligoclonal Bands - cerebrospinal fluid intrathecal fraction multiple sclerosis meta-analysis diagnosis index Cerebrospinal fluid kappa free light chains biomarker systematic review clinically isolated syndrome
ISSN:	1477-0970, 1477-0970
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Abstract	Intrathecal immunoglobulin-G synthesis is a hallmark of multiple sclerosis (MS), which can be detected by oligoclonal IgG bands (OCB) or by κ-free light chains (κ-FLC) in cerebrospinal fluid. To perform a systematic review and meta-analysis to evaluate whether κ-FLC index has similar diagnostic value to identify patients with clinically isolated syndrome (CIS) or MS compared to OCB, and to determine κ-FLC index cut-off. PubMed was searched for studies that assessed diagnostic sensitivity and specificity of κ-FLC index and OCB to discriminate CIS/MS patients from control subjects. Two reviewers following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines performed study eligibility assessment and data extraction. Findings from studies were analyzed with bivariate mixed models. A total of 32 studies were included in the meta-analysis to evaluate diagnostic value of κ-FLC index. Sensitivity and specificity ranged from 52% to 100% (weighted average: 88%) and 69% to 100% (89%) for κ-FLC index and from 37% to 100% (85%) and 74% to 100% (92%) for OCB. Mean difference of sensitivity and specificity between κ-FLC index and OCB was 2 and -4 percentage points. Diagnostic accuracy determined by mixed models revealed no significant difference between κ-FLC index and OCB. A discriminatory cut-off for κ-FLC index was determined at 6.1. The findings indicate that κ-FLC index has similar diagnostic accuracy in MS as OCB.
AbstractList	Intrathecal immunoglobulin-G synthesis is a hallmark of multiple sclerosis (MS), which can be detected by oligoclonal IgG bands (OCB) or by κ-free light chains (κ-FLC) in cerebrospinal fluid.BACKGROUNDIntrathecal immunoglobulin-G synthesis is a hallmark of multiple sclerosis (MS), which can be detected by oligoclonal IgG bands (OCB) or by κ-free light chains (κ-FLC) in cerebrospinal fluid.To perform a systematic review and meta-analysis to evaluate whether κ-FLC index has similar diagnostic value to identify patients with clinically isolated syndrome (CIS) or MS compared to OCB, and to determine κ-FLC index cut-off.OBJECTIVETo perform a systematic review and meta-analysis to evaluate whether κ-FLC index has similar diagnostic value to identify patients with clinically isolated syndrome (CIS) or MS compared to OCB, and to determine κ-FLC index cut-off.PubMed was searched for studies that assessed diagnostic sensitivity and specificity of κ-FLC index and OCB to discriminate CIS/MS patients from control subjects. Two reviewers following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines performed study eligibility assessment and data extraction. Findings from studies were analyzed with bivariate mixed models.METHODSPubMed was searched for studies that assessed diagnostic sensitivity and specificity of κ-FLC index and OCB to discriminate CIS/MS patients from control subjects. Two reviewers following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines performed study eligibility assessment and data extraction. Findings from studies were analyzed with bivariate mixed models.A total of 32 studies were included in the meta-analysis to evaluate diagnostic value of κ-FLC index. Sensitivity and specificity ranged from 52% to 100% (weighted average: 88%) and 69% to 100% (89%) for κ-FLC index and from 37% to 100% (85%) and 74% to 100% (92%) for OCB. Mean difference of sensitivity and specificity between κ-FLC index and OCB was 2 and -4 percentage points. Diagnostic accuracy determined by mixed models revealed no significant difference between κ-FLC index and OCB. A discriminatory cut-off for κ-FLC index was determined at 6.1.RESULTSA total of 32 studies were included in the meta-analysis to evaluate diagnostic value of κ-FLC index. Sensitivity and specificity ranged from 52% to 100% (weighted average: 88%) and 69% to 100% (89%) for κ-FLC index and from 37% to 100% (85%) and 74% to 100% (92%) for OCB. Mean difference of sensitivity and specificity between κ-FLC index and OCB was 2 and -4 percentage points. Diagnostic accuracy determined by mixed models revealed no significant difference between κ-FLC index and OCB. A discriminatory cut-off for κ-FLC index was determined at 6.1.The findings indicate that κ-FLC index has similar diagnostic accuracy in MS as OCB.CONCLUSIONThe findings indicate that κ-FLC index has similar diagnostic accuracy in MS as OCB. Intrathecal immunoglobulin-G synthesis is a hallmark of multiple sclerosis (MS), which can be detected by oligoclonal IgG bands (OCB) or by κ-free light chains (κ-FLC) in cerebrospinal fluid. To perform a systematic review and meta-analysis to evaluate whether κ-FLC index has similar diagnostic value to identify patients with clinically isolated syndrome (CIS) or MS compared to OCB, and to determine κ-FLC index cut-off. PubMed was searched for studies that assessed diagnostic sensitivity and specificity of κ-FLC index and OCB to discriminate CIS/MS patients from control subjects. Two reviewers following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines performed study eligibility assessment and data extraction. Findings from studies were analyzed with bivariate mixed models. A total of 32 studies were included in the meta-analysis to evaluate diagnostic value of κ-FLC index. Sensitivity and specificity ranged from 52% to 100% (weighted average: 88%) and 69% to 100% (89%) for κ-FLC index and from 37% to 100% (85%) and 74% to 100% (92%) for OCB. Mean difference of sensitivity and specificity between κ-FLC index and OCB was 2 and -4 percentage points. Diagnostic accuracy determined by mixed models revealed no significant difference between κ-FLC index and OCB. A discriminatory cut-off for κ-FLC index was determined at 6.1. The findings indicate that κ-FLC index has similar diagnostic accuracy in MS as OCB.
Author	Tumani, Hayrettin Teunissen, Charlotte Deisenhammer, Florian Saadeh, Ruba Zetterberg, Henrik Gnanapavan, Sharmilee Villar, Luisa M Berek, Klaus Kaplan, Batia Khalil, Michael Arrambide, Georgina Hegen, Harald Willrich, Maria Alice V Walde, Janette
Author_xml	– sequence: 1 givenname: Harald surname: Hegen fullname: Hegen, Harald organization: Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria – sequence: 2 givenname: Janette orcidid: 0000-0002-1241-5292 surname: Walde fullname: Walde, Janette organization: Department of Statistics, Faculty of Economics and Statistics, University of Innsbruck, Innsbruck, Austria – sequence: 3 givenname: Klaus orcidid: 0000-0003-2755-2043 surname: Berek fullname: Berek, Klaus organization: Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria – sequence: 4 givenname: Georgina orcidid: 0000-0002-2657-5510 surname: Arrambide fullname: Arrambide, Georgina organization: Centre d'Esclerosi Múltiple de Catalunya, Department of Neurology/Neuroimmunology, Hospital Universitari Vall d'Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain – sequence: 5 givenname: Sharmilee orcidid: 0000-0003-2817-9922 surname: Gnanapavan fullname: Gnanapavan, Sharmilee organization: Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK – sequence: 6 givenname: Batia surname: Kaplan fullname: Kaplan, Batia organization: Laboratory of Hematology, Sheba Medical Center, Ramat Gan, Israel – sequence: 7 givenname: Michael orcidid: 0000-0002-5350-3328 surname: Khalil fullname: Khalil, Michael organization: Department of Neurology, Medical University of Graz, Graz, Austria – sequence: 8 givenname: Ruba surname: Saadeh fullname: Saadeh, Ruba organization: Department of Laboratory Medicine and Pathology and Department of Neurology, Mayo Clinic, Rochester, MN, USA – sequence: 9 givenname: Charlotte orcidid: 0000-0002-4061-0837 surname: Teunissen fullname: Teunissen, Charlotte organization: Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam UMC, Amsterdam, The Netherlands – sequence: 10 givenname: Hayrettin surname: Tumani fullname: Tumani, Hayrettin organization: CSF Laboratory, Department of Neurology, University of Ulm, Ulm, Germany – sequence: 11 givenname: Luisa M surname: Villar fullname: Villar, Luisa M organization: Immunology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain – sequence: 12 givenname: Maria Alice V surname: Willrich fullname: Willrich, Maria Alice V organization: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA – sequence: 13 givenname: Henrik surname: Zetterberg fullname: Zetterberg, Henrik organization: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden/Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden/Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London, UK/UK Dementia Research Institute, University College London, London, UK/Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China – sequence: 14 givenname: Florian orcidid: 0000-0003-4541-8841 surname: Deisenhammer fullname: Deisenhammer, Florian organization: Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
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SubjectTerms	Biomarkers - cerebrospinal fluid Demyelinating Diseases Humans Immunoglobulin G - cerebrospinal fluid Immunoglobulin kappa-Chains - cerebrospinal fluid Multiple Sclerosis - cerebrospinal fluid Multiple Sclerosis - diagnosis Oligoclonal Bands - cerebrospinal fluid
Title	Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: A systematic review and meta-analysis
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