Ockhuizen, Theodorus

English

ARTS repository - University of Groningen

   University of GroningenGenetic aspects of monoclonal gammapathyOckhuizen, TheodorusIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:1979Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Ockhuizen, T. (1979). Genetic aspects of monoclonal gammapathy. s.n.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 08-06-2022Chapter 1INTRODUCTIONTradit ional ly,research in diseases associated with a monoclonal compo-nent is one of the scienti f ic interests on the Department of InternalMedicine, University Hospital Groningen, The Netherlands. The studyreported in this thesis and performed in the Immunochemical Iaborarory, isto be regarded as a continuation of this research-line.The etiology of a monoclonal gammopathy is st i l l  an open quesrion.Reported multiple occurrence of monoclonal components and other immu-noglobulin abnormalities within families suggested the influence of geneti-cally determined factors. In order to trace such factors Fesren srarted tn7970a systematic study of family me'nbers of patients with myelomatosis, one ofthe clinical entities associated with an M-componen t. In I97 4 in his rhesisFesten reported on serum immunoglobulin levels in first-degree relatives ofpatients with myelomatosis. The serum immunoglobulin levels beingregarded as a refiection of the genetically controlled magnitude of immuneresponsiveness.In the present thesis research has been focussed on twoaddit ionalgeneti-cally determined factors, which could play a recognizable role in the onset ofmonoclonal gammopathy. In an extension of the family study the influenceof a disturbance in the genetic control of the heterogeneity of an immuneresponse has been studied in three families with multiple occurrence ofM-components. The second factor studied in this thesis is the genetic controlof immunoglobulin structure. A patient with two M-components in hisserum was investigated in terms of the relat ionship in strucrure and cel lularlocal izat ion of biosynthesis of both monoclonal proteins.The complexity and the many aspects of the present study gave rise to adetailed chapter 2. The structure of the immunoglobulin molecule isreviewed. Special attention is payed on idiotypy because antisera raisedagainst idiotypic determinants of M-components form an importantexperimental tool in this study. The genetic control of the immune responseis ample discussed. Data on the genetic conrrol of immunoglobulin srrucrureare summarized in view of the experimenrs on double gammoparhy(reported in chapter 4). The genetic conrrol of the magnirude of the immuneresponse is discussed in relation to the famiiy study which preceded thepresent one. The genetic control of rhe heterogeneity of an immuneresponse is reviewed because the hypothesis tested in our part of the familystudy is mainly based on these data (reported in chapter 3). B-cellproliferative diseases are briefly mentioned in order to stress their closerelationship. Finally, a survey is given on the familial occurrence ofimmunoglobulin abnormalities and on double gammopathy.The experimental data are comprised in two chapters. In chapter 3 ourhypothesis that an inherited restriction in the number of available V-regiongenes contributes to a genetic predisposition for monoclonal gammopathy istested. Results are shown and discussed of experiments performed with ahemagglutination inhibition technique and with a radiobinding inhibitionassay. In chapter 4 results are described of a study on a patient with doublegammopathy. Idiotypic antisera, raised against the distinctive M-componen ts  we re  app l i ed  i n  rad io immunoassays  and  i nimmunofluorescence studies of bone marrow smears.In chapter 5 the experimental data from chapter 3 and 4are discussed withregard to their contribution to the understanding of the genetics of theimmune response. Finally, a summary is given in English and Dutch,followed bv a list of references.

Genetic aspects of monoclonal gammapathy

https://pure.rug.nl/ws/files/14512084/Ockhuizen.PDF

Genetic aspects of monoclonal gammapathy

Abstract

Similar works

Full text

Available Versions

ARTS repository - University of Groningen