Unknown

Dataset Information

0

Distinct oligoclonal band antibodies in multiple sclerosis recognize ubiquitous self-proteins.


ABSTRACT: Oligoclonal Ig bands (OCBs) of the cerebrospinal fluid are a hallmark of multiple sclerosis (MS), a disabling inflammatory disease of the central nervous system (CNS). OCBs are locally produced by clonally expanded antigen-experienced B cells and therefore are believed to hold an important clue to the pathogenesis. However, their target antigens have remained unknown, mainly because it was thus far not possible to isolate distinct OCBs against a background of polyclonal antibodies. To overcome this obstacle, we copurified disulfide-linked Ig heavy and light chains from distinct OCBs for concurrent analysis by mass spectrometry and aligned patient-specific peptides to corresponding transcriptome databases. This method revealed the full-length sequences of matching chains from distinct OCBs, allowing for antigen searches using recombinant OCB antibodies. As validation, we demonstrate that an OCB antibody from a patient with an infectious CNS disorder, neuroborreliosis, recognized a Borrelia protein. Next, we produced six recombinant antibodies from four MS patients and identified three different autoantigens. All of them are conformational epitopes of ubiquitous intracellular proteins not specific to brain tissue. Our findings indicate that the B-cell response in MS is heterogeneous and partly directed against intracellular autoantigens released during tissue destruction. In addition to helping elucidate the role of B cells in MS, our approach allows the identification of target antigens of OCB antibodies in other neuroinflammatory diseases and the production of therapeutic antibodies in infectious CNS diseases.

SUBMITTER: Brandle SM 

PROVIDER: S-EPMC4948369 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Distinct oligoclonal band antibodies in multiple sclerosis recognize ubiquitous self-proteins.

Brändle Simone M SM   Obermeier Birgit B   Senel Makbule M   Bruder Jessica J   Mentele Reinhard R   Khademi Mohsen M   Olsson Tomas T   Tumani Hayrettin H   Kristoferitsch Wolfgang W   Lottspeich Friedrich F   Wekerle Hartmut H   Hohlfeld Reinhard R   Dornmair Klaus K  

Proceedings of the National Academy of Sciences of the United States of America 20160620 28


Oligoclonal Ig bands (OCBs) of the cerebrospinal fluid are a hallmark of multiple sclerosis (MS), a disabling inflammatory disease of the central nervous system (CNS). OCBs are locally produced by clonally expanded antigen-experienced B cells and therefore are believed to hold an important clue to the pathogenesis. However, their target antigens have remained unknown, mainly because it was thus far not possible to isolate distinct OCBs against a background of polyclonal antibodies. To overcome t  ...[more]

Similar Datasets

| S-EPMC7034880 | biostudies-literature
| S-EPMC3589422 | biostudies-literature
| S-EPMC5180199 | biostudies-literature
| S-EPMC7431217 | biostudies-literature
| S-EPMC3961546 | biostudies-literature
| S-EPMC3681825 | biostudies-literature
| S-EPMC4861052 | biostudies-literature
| S-EPMC7866405 | biostudies-literature
| S-EPMC4066985 | biostudies-literature
| S-EPMC9650197 | biostudies-literature