Autoantibodies to myelin basic protein (MBP) in healthy individuals and in patients with multiple sclerosis: a role in regulating cytokine responses to MBP

Chris Juul Hedegaard, Ning Chen, Finn Thorup Sellebjerg, Per Soelberg Sørensen, R Graham Q Leslie, Klaus Bendtzen, Claus Kim Hostein Nielsen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Anti-myelin basic protein (-MBP) autoantibodies have generally been considered to be absent from sera from healthy individuals, but to be detectable in sera from some patients with multiple sclerosis (MS). However, their pathogenic role is uncertain. We demonstrate the presence of MBP-reactive autoantibodies in sera from 17 healthy individuals and 17 MS patients. The addition of MBP to the sera caused a dose-dependent deposition of MBP and co-deposition of immunoglobulin M (IgM) and fragments of complement component 3 (C3) on allogeneic monocytes. Calcium chelation abrogated the immunoglobulin deposition, indicating that formation of complement-activating immune complexes played a role in the binding process. Furthermore, MBP elicited tumour necrosis factor (TNF)-alpha and interleukin (IL)-10 production by normal mononuclear cells in the presence of serum from both patients and controls. Mononuclear cells from MS patients responded to MBP with the production of interferon (IFN)-gamma, IL-4 and IL-5, in addition to TNF-alpha and IL-10. The production of IFN-gamma and IL-5 was increased when MS serum was added rather than normal serum. Denaturation of MBP strongly inhibited MBP deposition and the MBP-induced IgM deposition and cytokine production, indicating that these events were facilitated by autoantibodies recognizing conformational epitopes on MBP. We infer that MBP-elicited TNF-alpha and IL-10 responses are promoted to equal extents by naturally occurring MBP autoantibodies and autoantibodies contained in MS sera. However, the latter seem to be more efficient in facilitating the production of IFN-gamma and IL-5.
OriginalsprogEngelsk
TidsskriftImmunology
Vol/bind128
Udgave nummer1 Suppl
Sider (fra-til)e451-61
ISSN0019-2805
DOI
StatusUdgivet - 2009

Fingeraftryk

Myelin Basic Protein
Serum
Interleukin-5
Interleukin-10
Interferon-gamma
Tumor Necrosis Factor-alpha
Interleukin-4

Citer dette

Hedegaard, C. J., Chen, N., Sellebjerg, F. T., Sørensen, P. S., Leslie, R. G. Q., Bendtzen, K., & Nielsen, C. K. H. (2009). Autoantibodies to myelin basic protein (MBP) in healthy individuals and in patients with multiple sclerosis: a role in regulating cytokine responses to MBP. Immunology, 128(1 Suppl), e451-61. https://doi.org/10.1111/j.1365-2567.2008.02999.x
Hedegaard, Chris Juul ; Chen, Ning ; Sellebjerg, Finn Thorup ; Sørensen, Per Soelberg ; Leslie, R Graham Q ; Bendtzen, Klaus ; Nielsen, Claus Kim Hostein. / Autoantibodies to myelin basic protein (MBP) in healthy individuals and in patients with multiple sclerosis: a role in regulating cytokine responses to MBP. I: Immunology. 2009 ; Bind 128, Nr. 1 Suppl. s. e451-61.
@article{911b3668b80448229498ebecbd6f3d09,
title = "Autoantibodies to myelin basic protein (MBP) in healthy individuals and in patients with multiple sclerosis: a role in regulating cytokine responses to MBP",
abstract = "Anti-myelin basic protein (-MBP) autoantibodies have generally been considered to be absent from sera from healthy individuals, but to be detectable in sera from some patients with multiple sclerosis (MS). However, their pathogenic role is uncertain. We demonstrate the presence of MBP-reactive autoantibodies in sera from 17 healthy individuals and 17 MS patients. The addition of MBP to the sera caused a dose-dependent deposition of MBP and co-deposition of immunoglobulin M (IgM) and fragments of complement component 3 (C3) on allogeneic monocytes. Calcium chelation abrogated the immunoglobulin deposition, indicating that formation of complement-activating immune complexes played a role in the binding process. Furthermore, MBP elicited tumour necrosis factor (TNF)-alpha and interleukin (IL)-10 production by normal mononuclear cells in the presence of serum from both patients and controls. Mononuclear cells from MS patients responded to MBP with the production of interferon (IFN)-gamma, IL-4 and IL-5, in addition to TNF-alpha and IL-10. The production of IFN-gamma and IL-5 was increased when MS serum was added rather than normal serum. Denaturation of MBP strongly inhibited MBP deposition and the MBP-induced IgM deposition and cytokine production, indicating that these events were facilitated by autoantibodies recognizing conformational epitopes on MBP. We infer that MBP-elicited TNF-alpha and IL-10 responses are promoted to equal extents by naturally occurring MBP autoantibodies and autoantibodies contained in MS sera. However, the latter seem to be more efficient in facilitating the production of IFN-gamma and IL-5.",
keywords = "Adult, Autoantibodies, Calcium, Complement C3, Female, Humans, Immunoglobulin G, Immunoglobulin M, Interferon-gamma, Interleukin-10, Interleukin-4, Interleukin-5, Leukocytes, Mononuclear, Male, Multiple Sclerosis, Myelin Basic Proteins, Tumor Necrosis Factor-alpha",
author = "Hedegaard, {Chris Juul} and Ning Chen and Sellebjerg, {Finn Thorup} and S{\o}rensen, {Per Soelberg} and Leslie, {R Graham Q} and Klaus Bendtzen and Nielsen, {Claus Kim Hostein}",
year = "2009",
doi = "10.1111/j.1365-2567.2008.02999.x",
language = "English",
volume = "128",
pages = "e451--61",
journal = "Immunology",
issn = "0019-2805",
publisher = "Wiley-Blackwell",
number = "1 Suppl",

}

Hedegaard, CJ, Chen, N, Sellebjerg, FT, Sørensen, PS, Leslie, RGQ, Bendtzen, K & Nielsen, CKH 2009, 'Autoantibodies to myelin basic protein (MBP) in healthy individuals and in patients with multiple sclerosis: a role in regulating cytokine responses to MBP', Immunology, bind 128, nr. 1 Suppl, s. e451-61. https://doi.org/10.1111/j.1365-2567.2008.02999.x

Autoantibodies to myelin basic protein (MBP) in healthy individuals and in patients with multiple sclerosis: a role in regulating cytokine responses to MBP. / Hedegaard, Chris Juul; Chen, Ning; Sellebjerg, Finn Thorup; Sørensen, Per Soelberg; Leslie, R Graham Q; Bendtzen, Klaus; Nielsen, Claus Kim Hostein.

I: Immunology, Bind 128, Nr. 1 Suppl, 2009, s. e451-61.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Autoantibodies to myelin basic protein (MBP) in healthy individuals and in patients with multiple sclerosis: a role in regulating cytokine responses to MBP

AU - Hedegaard, Chris Juul

AU - Chen, Ning

AU - Sellebjerg, Finn Thorup

AU - Sørensen, Per Soelberg

AU - Leslie, R Graham Q

AU - Bendtzen, Klaus

AU - Nielsen, Claus Kim Hostein

PY - 2009

Y1 - 2009

N2 - Anti-myelin basic protein (-MBP) autoantibodies have generally been considered to be absent from sera from healthy individuals, but to be detectable in sera from some patients with multiple sclerosis (MS). However, their pathogenic role is uncertain. We demonstrate the presence of MBP-reactive autoantibodies in sera from 17 healthy individuals and 17 MS patients. The addition of MBP to the sera caused a dose-dependent deposition of MBP and co-deposition of immunoglobulin M (IgM) and fragments of complement component 3 (C3) on allogeneic monocytes. Calcium chelation abrogated the immunoglobulin deposition, indicating that formation of complement-activating immune complexes played a role in the binding process. Furthermore, MBP elicited tumour necrosis factor (TNF)-alpha and interleukin (IL)-10 production by normal mononuclear cells in the presence of serum from both patients and controls. Mononuclear cells from MS patients responded to MBP with the production of interferon (IFN)-gamma, IL-4 and IL-5, in addition to TNF-alpha and IL-10. The production of IFN-gamma and IL-5 was increased when MS serum was added rather than normal serum. Denaturation of MBP strongly inhibited MBP deposition and the MBP-induced IgM deposition and cytokine production, indicating that these events were facilitated by autoantibodies recognizing conformational epitopes on MBP. We infer that MBP-elicited TNF-alpha and IL-10 responses are promoted to equal extents by naturally occurring MBP autoantibodies and autoantibodies contained in MS sera. However, the latter seem to be more efficient in facilitating the production of IFN-gamma and IL-5.

AB - Anti-myelin basic protein (-MBP) autoantibodies have generally been considered to be absent from sera from healthy individuals, but to be detectable in sera from some patients with multiple sclerosis (MS). However, their pathogenic role is uncertain. We demonstrate the presence of MBP-reactive autoantibodies in sera from 17 healthy individuals and 17 MS patients. The addition of MBP to the sera caused a dose-dependent deposition of MBP and co-deposition of immunoglobulin M (IgM) and fragments of complement component 3 (C3) on allogeneic monocytes. Calcium chelation abrogated the immunoglobulin deposition, indicating that formation of complement-activating immune complexes played a role in the binding process. Furthermore, MBP elicited tumour necrosis factor (TNF)-alpha and interleukin (IL)-10 production by normal mononuclear cells in the presence of serum from both patients and controls. Mononuclear cells from MS patients responded to MBP with the production of interferon (IFN)-gamma, IL-4 and IL-5, in addition to TNF-alpha and IL-10. The production of IFN-gamma and IL-5 was increased when MS serum was added rather than normal serum. Denaturation of MBP strongly inhibited MBP deposition and the MBP-induced IgM deposition and cytokine production, indicating that these events were facilitated by autoantibodies recognizing conformational epitopes on MBP. We infer that MBP-elicited TNF-alpha and IL-10 responses are promoted to equal extents by naturally occurring MBP autoantibodies and autoantibodies contained in MS sera. However, the latter seem to be more efficient in facilitating the production of IFN-gamma and IL-5.

KW - Adult

KW - Autoantibodies

KW - Calcium

KW - Complement C3

KW - Female

KW - Humans

KW - Immunoglobulin G

KW - Immunoglobulin M

KW - Interferon-gamma

KW - Interleukin-10

KW - Interleukin-4

KW - Interleukin-5

KW - Leukocytes, Mononuclear

KW - Male

KW - Multiple Sclerosis

KW - Myelin Basic Proteins

KW - Tumor Necrosis Factor-alpha

U2 - 10.1111/j.1365-2567.2008.02999.x

DO - 10.1111/j.1365-2567.2008.02999.x

M3 - Journal article

VL - 128

SP - e451-61

JO - Immunology

JF - Immunology

SN - 0019-2805

IS - 1 Suppl

ER -