Lineage tree analysis of immunoglobulin variable-region gene mutations in autoimmune diseases: Chronic activation, normal selection

Avital Steiman-Shimony; Hanna Edelman; Anat Hutzler; Michal Barak; Neta S. Zuckerman; Gitit Shahaf; Deborah Dunn-Walters; David I. Stott; Roshini S. Abraham; Ramit Mehr

doi:10.1016/j.cellimm.2007.01.009

Lineage tree analysis of immunoglobulin variable-region gene mutations in autoimmune diseases: Chronic activation, normal selection

Avital Steiman-Shimony, Hanna Edelman, Anat Hutzler, Michal Barak, Neta S. Zuckerman, Gitit Shahaf, Deborah Dunn-Walters, David I. Stott, Roshini S. Abraham, Ramit Mehr

The Mina and Everard Goodman Faculty of Life Sciences

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

Autoimmune diseases show high diversity in the affected organs, clinical manifestations and disease dynamics. Yet they all share common features, such as the ectopic germinal centers found in many affected tissues. Lineage trees depict the diversification, via somatic hypermutation (SHM), of immunoglobulin variable-region (IGV) genes. We previously developed an algorithm for quantifying the graphical properties of IGV gene lineage trees, allowing evaluation of the dynamical interplay between SHM and antigen-driven selection in different lymphoid tissues, species, and disease situations. Here, we apply this method to ectopic GC B cell clones from patients with Myasthenia Gravis, Rheumatoid Arthritis, and Sjögren's Syndrome, using data scaling to minimize the effects of the large variability due to methodological differences between groups. Autoimmune trees were found to be significantly larger relative to normal controls. In contrast, comparison of the measurements for tree branching indicated that similar selection pressure operates on autoimmune and normal control clones.

Original language	English
Pages (from-to)	130-136
Number of pages	7
Journal	Cellular Immunology
Volume	244
Issue number	2
DOIs	https://doi.org/10.1016/j.cellimm.2007.01.009
State	Published - Dec 2006

Bibliographical note

Funding Information:
The authors are indebted to Osnat Steiman for editing the manuscript. The work was part of Avital Steiman-Shimony’s studies towards an MSc degree in Bar-Ilan University, and was supported in parts by the following Grants: the Israel Science Foundation Grants number 759/01-1 and 546, an Israel Cancer Research Fund project Grant, a Systems Biology prize Grant from Teva Pharmaceuticals, a Human Frontiers Science Program Young Investigator Grant, and a Swedish Foundation for Strategic Research Grant funding the Strategic Research Center for studies on Integrative Recognition in the Immune System (IRIS), Karolinska Institute, Stockholm, Sweden (to RM); a BBSRC Science of Ageing initiative Grant (to DDW); Grants from the EC Marie Curie Research Fellowship (the SS work), and The Wellcome Trust (the MG work), to DIS; and a Hematological Malignancies Research Fund, Mayo Clinic Grant (to RSA).

Funding

The authors are indebted to Osnat Steiman for editing the manuscript. The work was part of Avital Steiman-Shimony’s studies towards an MSc degree in Bar-Ilan University, and was supported in parts by the following Grants: the Israel Science Foundation Grants number 759/01-1 and 546, an Israel Cancer Research Fund project Grant, a Systems Biology prize Grant from Teva Pharmaceuticals, a Human Frontiers Science Program Young Investigator Grant, and a Swedish Foundation for Strategic Research Grant funding the Strategic Research Center for studies on Integrative Recognition in the Immune System (IRIS), Karolinska Institute, Stockholm, Sweden (to RM); a BBSRC Science of Ageing initiative Grant (to DDW); Grants from the EC Marie Curie Research Fellowship (the SS work), and The Wellcome Trust (the MG work), to DIS; and a Hematological Malignancies Research Fund, Mayo Clinic Grant (to RSA).

Funders	Funder number
BBSRC Science of Ageing
Teva Pharmaceuticals
Mayo Clinic
Israel Cancer Research Fund
Wellcome Trust
Center for Strategic Research
Medical Research Council	G0000160
Marie Curie
Stiftelsen för Strategisk Forskning
Israel Science Foundation	759/01-1, 546
Karolinska Institutet

Keywords

Germinal centers
Myasthenia Gravis (MG)
Rheumatoid Arthritis (RA)
Sjögren's Syndrome (SS)
Somatic hypermutation

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10.1016/j.cellimm.2007.01.009

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Steiman-Shimony, A., Edelman, H., Hutzler, A., Barak, M., Zuckerman, N. S., Shahaf, G., Dunn-Walters, D., Stott, D. I., Abraham, R. S., & Mehr, R. (2006). Lineage tree analysis of immunoglobulin variable-region gene mutations in autoimmune diseases: Chronic activation, normal selection. Cellular Immunology, 244(2), 130-136. https://doi.org/10.1016/j.cellimm.2007.01.009

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title = "Lineage tree analysis of immunoglobulin variable-region gene mutations in autoimmune diseases: Chronic activation, normal selection",

abstract = "Autoimmune diseases show high diversity in the affected organs, clinical manifestations and disease dynamics. Yet they all share common features, such as the ectopic germinal centers found in many affected tissues. Lineage trees depict the diversification, via somatic hypermutation (SHM), of immunoglobulin variable-region (IGV) genes. We previously developed an algorithm for quantifying the graphical properties of IGV gene lineage trees, allowing evaluation of the dynamical interplay between SHM and antigen-driven selection in different lymphoid tissues, species, and disease situations. Here, we apply this method to ectopic GC B cell clones from patients with Myasthenia Gravis, Rheumatoid Arthritis, and Sj{\"o}gren's Syndrome, using data scaling to minimize the effects of the large variability due to methodological differences between groups. Autoimmune trees were found to be significantly larger relative to normal controls. In contrast, comparison of the measurements for tree branching indicated that similar selection pressure operates on autoimmune and normal control clones.",

keywords = "Germinal centers, Myasthenia Gravis (MG), Rheumatoid Arthritis (RA), Sj{\"o}gren's Syndrome (SS), Somatic hypermutation",

author = "Avital Steiman-Shimony and Hanna Edelman and Anat Hutzler and Michal Barak and Zuckerman, {Neta S.} and Gitit Shahaf and Deborah Dunn-Walters and Stott, {David I.} and Abraham, {Roshini S.} and Ramit Mehr",

note = "Funding Information: The authors are indebted to Osnat Steiman for editing the manuscript. The work was part of Avital Steiman-Shimony{\textquoteright}s studies towards an MSc degree in Bar-Ilan University, and was supported in parts by the following Grants: the Israel Science Foundation Grants number 759/01-1 and 546, an Israel Cancer Research Fund project Grant, a Systems Biology prize Grant from Teva Pharmaceuticals, a Human Frontiers Science Program Young Investigator Grant, and a Swedish Foundation for Strategic Research Grant funding the Strategic Research Center for studies on Integrative Recognition in the Immune System (IRIS), Karolinska Institute, Stockholm, Sweden (to RM); a BBSRC Science of Ageing initiative Grant (to DDW); Grants from the EC Marie Curie Research Fellowship (the SS work), and The Wellcome Trust (the MG work), to DIS; and a Hematological Malignancies Research Fund, Mayo Clinic Grant (to RSA). ",

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AU - Shahaf, Gitit

AU - Dunn-Walters, Deborah

AU - Stott, David I.

AU - Abraham, Roshini S.

AU - Mehr, Ramit

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Lineage tree analysis of immunoglobulin variable-region gene mutations in autoimmune diseases: Chronic activation, normal selection

Abstract

Bibliographical note

Funding

Keywords

Access to Document

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