The gut ecosystem, constituted by the intestinal bacteria and their human host, is a rather unknown area. Since about 400 different species of bacteria are able to live in the gut, studying this total ecosystem harbors enormous difficulties. Yet such kind of a study is important, because there are experimental data directing towards a possible role of these intestinal bacteria in a systemic autoimmune disease such as Systemic Lupus Erythematosus (SLE).  ...

Zie: Summary

Apperloo-Renkema, Hermina Zwierina,

Apperloo-Renkema, Hermina Zwierina

ARTS repository - University of Groningen

   University of GroningenAspects of the host-microflora interaction and its possible impact on auto-immune diseaseApperloo-Renkema, Hermina ZwierinaIMPORTANT 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:1993Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Apperloo-Renkema, H. Z. (1993). Aspects of the host-microflora interaction and its possible impact on auto-immune disease. 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: 08-06-2022/Aspects tf the host-micnfilora interactionThe gut ecosystem, constituted by the intestinal bacteria and their human host, is a ratherunknown area. Since about 400 different species of bacteria are able to live in the gut,studying this total ecosystem harbors enorÍnous diff iculties. Yet such kind of a study isimportant, because there are experimental data directing towiu'ds a possible roie of theseintestinal bacteria in a systemic autoimmune disease such as Systemic Lupus Erythematosus(SLE). Therefore two tools were elaborated irr this thesis that may provide insight in certainaspects of functioning of the gut ecosystem.The first tool is measurement of Colonization Resistance (CR). CR is the resistance of thegastrointestinal tract against colonization by ingested bacteria and is mainly ascribed to theanaerobic bacteria in the gut. A good CR implies efficient control of the growth andtherewith chance of translocation of potentially pathogenic bacteria across the gut wall.Upon a decrease in CR translocation of certain bacterial species may increase and the hostmay produce cLntibacterial ntibodies. CR correlates inversely with the number of differentbiotypes of Enterohacteriaceae isolated from faecal samples. In chapter 2 the naturalvariation in the nun'rber of different biotypes of Entct'obacteriaceue per faecal sample wasassessed in healthy individuals. It followed that reliable determination of the mean numberof diffèrent biotypes, the inverse of which is representative for the CR of zur individual,required study of fbur faecal samples of this individual. In chapter 4 this way of rneasuringCR in humirns was coÍnpared with the golden standard for measuring CR: 10 healthyindividuals were contaminated orally with a neomycin resistant E.r:o/l (NR-E.coll) strain andthe faecal concentration of this strain was measured during l4 days after the contirmination.this faecal concentration being the measure for the CR. Both rnethods for CR werecorrelated significantly (P<0.01 ).The second tool is irrununor.norphometry. Inununomorphometry combines irnage analysisand indirect intmunofluorescence. The antibacterial antibodies thus measured are a directconsequence of the interaction between the host and his microflora. First of all we showedin chapter 3 that it is possible to measure titres of urtibodies directed against pure culturesof Enterobacteriaceae by combining classical indirect immunofluorescence (IIF) withreading of the IIF slides by an image processing system. Reading of IIF titres by the imageprocessing system was nrore accurate tir iur eye reading. With this nlethod serum antibodytitres against the NR-E.coll strain, used for oral contiunination in chapter 4, were measured.Persons who elirninated the NR-E.coli strain fastest fronr their intestinal tract didnot producehighest antibody titres against ttre NR-E.c'oii strain. On the contriuy, the longer the NR-E.coli slrain remained in the digestive tract the higher the antibody titres against the NR-E.coli. Therefbre. elimination of an oral contaminant fiom the intestines is not IgG or IgMantibody mediated.Faecal bacteria can be divided in morphologically different groups by image analysis.Combined with the IIF technique it results in immunornorphometry described in chapter -5,1008. Summarywhich enables detennination of plasma antibody titres of IgA. IgG and IgM isotype againstmorphologically defined groups (morphotypes) of faecal bacteria in healthy irrdividuals.Each individual has his own pattern of antibacterial antibodies.Immunomorphonretry can be applied to study specificit ies of the serurn antibodies againstfaecal bacteria. In chapter 6 it was shown that healthy individuuls not only possessantibodies against l"reir own autochthonous intestinal bacteria, but they also have antibodiesof both the IgA, IgG and IgM isotype against allogenous faecal bacteria. These antibodieswere left in their sera after removal of the antibodies against the autochthonous faecalbacteria by absorption. Relatively more IgA antibodies appeared to be directed againstallogenous than against autochthonous faecal bacteria, indicating that the autochthonousmicroflora is less immunogenic than the allogenous microflora or that tolerance existstowards the autochthonous nricroflora. If a person has many antibodies of IgA and IgGisotype against his own microflora, this could mean that his indigenous microflora is notvery stable. This could indicate that he could have had the chance of rnounting a specifichumoral immune response against malv species of allogenous anaerobic intestinal bacteria.resulting in antibodies of IgA and IgG isotype against a wide range of allogenous intestinalbacteria. Indeed we found that persons who reacted with specific untibodies to manybacteria of their own microflora, also tended to react specifically to bacteria in tbeallogenous microflora of the other healthy volunteers.Both tools described above were used in our study on the possible role of the indigenousintestintrl microflora in SLE. in chapter 7. The CR of the indigenous intestina.l rnicrofloratended to be lower in SLE patients than in healthy individuals. Quantitative diÍterences inthe humori-rl esponse to indigenous intestinal bacteria were found between SLE patients andhealthy individuals. IgM titres were found to be lower both in patients with active andinactive SLE as compared to healthy individuals. Specific (IgG) antibacterial ;urtibodyresponses were increased in the group with inactive SLE. However, in the group with activeSLE a much lower titre of IgG antibacterial antibody titres was found, aithough theconcentration of total plasma IgG was almost doubled in cornparison with theconcentrations in the group with inactive SLE.These results could indicate that in SLE patients more different bacteria rnay translocateacross the gut wall due to a lower CR. Some of these bactelia may serve as turtigen for theproduction of iLnti-bacterial iurtibodies crossreacting with DNA. IgM rurtibacterial ntibodytitres were decreased in patients with SLE indicating a ftri l ing network. As a result of thisfailing network and possibly of a lower CR, IgG antibacterial antibodies were increased inpatients with inactive SLE. However, the production of IgG anti-bacterial antibodies wasdecreased in patients with active SLE. This could be in fervour of increased. possiblyantigen driven, production of those antibodies that play a role in exacerbations of SLE, ormight be explained by usage of these IgG antibodies in immune complexes. The latter101Aspects of the host-mícroflora inter(k:tk)nexplation could point at a role of the antibacterial antibodies in the etiology of part of theexacerbations of human SLE.t02

English

Aspects of the host-microflora interaction and its possible impact on auto-immune disease

   University of GroningenAspects of the host-microflora interaction and its possible impact on auto-immune diseaseApperloo-Renkema, Hermina ZwierinaIMPORTANT 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:1993Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Apperloo-Renkema, H. Z. (1993). Aspects of the host-microflora interaction and its possible impact on auto-immune disease. 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: 09-09-2023/Aspects tf the host-micnfilora interactionThe gut ecosystem, constituted by the intestinal bacteria and their human host, is a ratherunknown area. Since about 400 different species of bacteria are able to live in the gut,studying this total ecosystem harbors enorÍnous diff iculties. Yet such kind of a study isimportant, because there are experimental data directing towiu'ds a possible roie of theseintestinal bacteria in a systemic autoimmune disease such as Systemic Lupus Erythematosus(SLE). Therefore two tools were elaborated irr this thesis that may provide insight in certainaspects of functioning of the gut ecosystem.The first tool is measurement of Colonization Resistance (CR). CR is the resistance of thegastrointestinal tract against colonization by ingested bacteria and is mainly ascribed to theanaerobic bacteria in the gut. A good CR implies efficient control of the growth andtherewith chance of translocation of potentially pathogenic bacteria across the gut wall.Upon a decrease in CR translocation of certain bacterial species may increase and the hostmay produce cLntibacterial ntibodies. CR correlates inversely with the number of differentbiotypes of Enterohacteriaceae isolated from faecal samples. In chapter 2 the naturalvariation in the nun'rber of different biotypes of Entct'obacteriaceue per faecal sample wasassessed in healthy individuals. It followed that reliable determination of the mean numberof diffèrent biotypes, the inverse of which is representative for the CR of zur individual,required study of fbur faecal samples of this individual. In chapter 4 this way of rneasuringCR in humirns was coÍnpared with the golden standard for measuring CR: 10 healthyindividuals were contaminated orally with a neomycin resistant E.r:o/l (NR-E.coll) strain andthe faecal concentration of this strain was measured during l4 days after the contirmination.this faecal concentration being the measure for the CR. Both rnethods for CR werecorrelated significantly (P<0.01 ).The second tool is irrununor.norphometry. Inununomorphometry combines irnage analysisand indirect intmunofluorescence. The antibacterial antibodies thus measured are a directconsequence of the interaction between the host and his microflora. First of all we showedin chapter 3 that it is possible to measure titres of urtibodies directed against pure culturesof Enterobacteriaceae by combining classical indirect immunofluorescence (IIF) withreading of the IIF slides by an image processing system. Reading of IIF titres by the imageprocessing system was nrore accurate tir iur eye reading. With this nlethod serum antibodytitres against the NR-E.coll strain, used for oral contiunination in chapter 4, were measured.Persons who elirninated the NR-E.coli strain fastest fronr their intestinal tract didnot producehighest antibody titres against ttre NR-E.c'oii strain. On the contriuy, the longer the NR-E.coli slrain remained in the digestive tract the higher the antibody titres against the NR-E.coli. Therefbre. elimination of an oral contaminant fiom the intestines is not IgG or IgMantibody mediated.Faecal bacteria can be divided in morphologically different groups by image analysis.Combined with the IIF technique it results in immunornorphometry described in chapter -5,1008. Summarywhich enables detennination of plasma antibody titres of IgA. IgG and IgM isotype againstmorphologically defined groups (morphotypes) of faecal bacteria in healthy irrdividuals.Each individual has his own pattern of antibacterial antibodies.Immunomorphonretry can be applied to study specificit ies of the serurn antibodies againstfaecal bacteria. In chapter 6 it was shown that healthy individuuls not only possessantibodies against l"reir own autochthonous intestinal bacteria, but they also have antibodiesof both the IgA, IgG and IgM isotype against allogenous faecal bacteria. These antibodieswere left in their sera after removal of the antibodies against the autochthonous faecalbacteria by absorption. Relatively more IgA antibodies appeared to be directed againstallogenous than against autochthonous faecal bacteria, indicating that the autochthonousmicroflora is less immunogenic than the allogenous microflora or that tolerance existstowards the autochthonous nricroflora. If a person has many antibodies of IgA and IgGisotype against his own microflora, this could mean that his indigenous microflora is notvery stable. This could indicate that he could have had the chance of rnounting a specifichumoral immune response against malv species of allogenous anaerobic intestinal bacteria.resulting in antibodies of IgA and IgG isotype against a wide range of allogenous intestinalbacteria. Indeed we found that persons who reacted with specific untibodies to manybacteria of their own microflora, also tended to react specifically to bacteria in tbeallogenous microflora of the other healthy volunteers.Both tools described above were used in our study on the possible role of the indigenousintestintrl microflora in SLE. in chapter 7. The CR of the indigenous intestina.l rnicrofloratended to be lower in SLE patients than in healthy individuals. Quantitative diÍterences inthe humori-rl esponse to indigenous intestinal bacteria were found between SLE patients andhealthy individuals. IgM titres were found to be lower both in patients with active andinactive SLE as compared to healthy individuals. Specific (IgG) antibacterial ;urtibodyresponses were increased in the group with inactive SLE. However, in the group with activeSLE a much lower titre of IgG antibacterial antibody titres was found, aithough theconcentration of total plasma IgG was almost doubled in cornparison with theconcentrations in the group with inactive SLE.These results could indicate that in SLE patients more different bacteria rnay translocateacross the gut wall due to a lower CR. Some of these bactelia may serve as turtigen for theproduction of iLnti-bacterial iurtibodies crossreacting with DNA. IgM rurtibacterial ntibodytitres were decreased in patients with SLE indicating a ftri l ing network. As a result of thisfailing network and possibly of a lower CR, IgG antibacterial antibodies were increased inpatients with inactive SLE. However, the production of IgG anti-bacterial antibodies wasdecreased in patients with active SLE. This could be in fervour of increased. possiblyantigen driven, production of those antibodies that play a role in exacerbations of SLE, ormight be explained by usage of these IgG antibodies in immune complexes. The latter101Aspects of the host-mícroflora inter(k:tk)nexplation could point at a role of the antibacterial antibodies in the etiology of part of theexacerbations of human SLE.t02

University of Groningen

   University of GroningenAspects of the host-microflora interaction and its possible impact on auto-immune diseaseApperloo-Renkema, Hermina ZwierinaIMPORTANT 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:1993Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Apperloo-Renkema, H. Z. (1993). Aspects of the host-microflora interaction and its possible impact on auto-immune disease. Groningen: 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).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: 12-11-2019/Aspects tf the host-micnfilora interactionThe gut ecosystem, constituted by the intestinal bacteria and their human host, is a ratherunknown area. Since about 400 different species of bacteria are able to live in the gut,studying this total ecosystem harbors enorÍnous diff iculties. Yet such kind of a study isimportant, because there are experimental data directing towiu'ds a possible roie of theseintestinal bacteria in a systemic autoimmune disease such as Systemic Lupus Erythematosus(SLE). Therefore two tools were elaborated irr this thesis that may provide insight in certainaspects of functioning of the gut ecosystem.The first tool is measurement of Colonization Resistance (CR). CR is the resistance of thegastrointestinal tract against colonization by ingested bacteria and is mainly ascribed to theanaerobic bacteria in the gut. A good CR implies efficient control of the growth andtherewith chance of translocation of potentially pathogenic bacteria across the gut wall.Upon a decrease in CR translocation of certain bacterial species may increase and the hostmay produce cLntibacterial ntibodies. CR correlates inversely with the number of differentbiotypes of Enterohacteriaceae isolated from faecal samples. In chapter 2 the naturalvariation in the nun'rber of different biotypes of Entct'obacteriaceue per faecal sample wasassessed in healthy individuals. It followed that reliable determination of the mean numberof diffèrent biotypes, the inverse of which is representative for the CR of zur individual,required study of fbur faecal samples of this individual. In chapter 4 this way of rneasuringCR in humirns was coÍnpared with the golden standard for measuring CR: 10 healthyindividuals were contaminated orally with a neomycin resistant E.r:o/l (NR-E.coll) strain andthe faecal concentration of this strain was measured during l4 days after the contirmination.this faecal concentration being the measure for the CR. Both rnethods for CR werecorrelated significantly (P<0.01 ).The second tool is irrununor.norphometry. Inununomorphometry combines irnage analysisand indirect intmunofluorescence. The antibacterial antibodies thus measured are a directconsequence of the interaction between the host and his microflora. First of all we showedin chapter 3 that it is possible to measure titres of urtibodies directed against pure culturesof Enterobacteriaceae by combining classical indirect immunofluorescence (IIF) withreading of the IIF slides by an image processing system. Reading of IIF titres by the imageprocessing system was nrore accurate tir iur eye reading. With this nlethod serum antibodytitres against the NR-E.coll strain, used for oral contiunination in chapter 4, were measured.Persons who elirninated the NR-E.coli strain fastest fronr their intestinal tract didnot producehighest antibody titres against ttre NR-E.c'oii strain. On the contriuy, the longer the NR-E.coli slrain remained in the digestive tract the higher the antibody titres against the NR-E.coli. Therefbre. elimination of an oral contaminant fiom the intestines is not IgG or IgMantibody mediated.Faecal bacteria can be divided in morphologically different groups by image analysis.Combined with the IIF technique it results in immunornorphometry described in chapter -5,1008. Summarywhich enables detennination of plasma antibody titres of IgA. IgG and IgM isotype againstmorphologically defined groups (morphotypes) of faecal bacteria in healthy irrdividuals.Each individual has his own pattern of antibacterial antibodies.Immunomorphonretry can be applied to study specificit ies of the serurn antibodies againstfaecal bacteria. In chapter 6 it was shown that healthy individuuls not only possessantibodies against l"reir own autochthonous intestinal bacteria, but they also have antibodiesof both the IgA, IgG and IgM isotype against allogenous faecal bacteria. These antibodieswere left in their sera after removal of the antibodies against the autochthonous faecalbacteria by absorption. Relatively more IgA antibodies appeared to be directed againstallogenous than against autochthonous faecal bacteria, indicating that the autochthonousmicroflora is less immunogenic than the allogenous microflora or that tolerance existstowards the autochthonous nricroflora. If a person has many antibodies of IgA and IgGisotype against his own microflora, this could mean that his indigenous microflora is notvery stable. This could indicate that he could have had the chance of rnounting a specifichumoral immune response against malv species of allogenous anaerobic intestinal bacteria.resulting in antibodies of IgA and IgG isotype against a wide range of allogenous intestinalbacteria. Indeed we found that persons who reacted with specific untibodies to manybacteria of their own microflora, also tended to react specifically to bacteria in tbeallogenous microflora of the other healthy volunteers.Both tools described above were used in our study on the possible role of the indigenousintestintrl microflora in SLE. in chapter 7. The CR of the indigenous intestina.l rnicrofloratended to be lower in SLE patients than in healthy individuals. Quantitative diÍterences inthe humori-rl esponse to indigenous intestinal bacteria were found between SLE patients andhealthy individuals. IgM titres were found to be lower both in patients with active andinactive SLE as compared to healthy individuals. Specific (IgG) antibacterial ;urtibodyresponses were increased in the group with inactive SLE. However, in the group with activeSLE a much lower titre of IgG antibacterial antibody titres was found, aithough theconcentration of total plasma IgG was almost doubled in cornparison with theconcentrations in the group with inactive SLE.These results could indicate that in SLE patients more different bacteria rnay translocateacross the gut wall due to a lower CR. Some of these bactelia may serve as turtigen for theproduction of iLnti-bacterial iurtibodies crossreacting with DNA. IgM rurtibacterial ntibodytitres were decreased in patients with SLE indicating a ftri l ing network. As a result of thisfailing network and possibly of a lower CR, IgG antibacterial antibodies were increased inpatients with inactive SLE. However, the production of IgG anti-bacterial antibodies wasdecreased in patients with active SLE. This could be in fervour of increased. possiblyantigen driven, production of those antibodies that play a role in exacerbations of SLE, ormight be explained by usage of these IgG antibodies in immune complexes. The latter101Aspects of the host-mícroflora inter(k:tk)nexplation could point at a role of the antibacterial antibodies in the etiology of part of theexacerbations of human SLE.t02

University of Groningen Digital Archive

NARCIS 

University of Groningen Research Database

  
 University of Groningen
Aspects of the host-microflora interaction and its possible impact on auto-immune disease
Apperloo-Renkema, Hermina Zwierina
IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from
it. Please check the document version below.
Document Version
Publisher's PDF, also known as Version of record
Publication date:
1993
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Apperloo-Renkema, H. Z. (1993). Aspects of the host-microflora interaction and its possible impact on auto-
immune disease Groningen: s.n.
Copyright
Other 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 the
author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).
Take-down policy
If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately
and investigate your claim.
Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the
number of authors shown on this cover page is limited to 10 maximum.
Download date: 11-02-2018
/Aspects tf the host-micnfilora interaction
The gut ecosystem, constituted by the intestinal bacteria and their human host, is a rather
unknown area. Since about 400 different species of bacteria are able to live in the gut,
studying this total ecosystem harbors enorÍnous diff iculties. Yet such kind of a study is
important, because there are experimental data directing towiu'ds a possible roie of these
intestinal bacteria in a systemic autoimmune disease such as Systemic Lupus Erythematosus
(SLE). Therefore two tools were elaborated irr this thesis that may provide insight in certain
aspects of functioning of the gut ecosystem.
The first tool is measurement of Colonization Resistance (CR). CR is the resistance of the
gastrointestinal tract against colonization by ingested bacteria and is mainly ascribed to the
anaerobic bacteria in the gut. A good CR implies efficient control of the growth and
therewith chance of translocation of potentially pathogenic bacteria across the gut wall.
Upon a decrease in CR translocation of certain bacterial species may increase and the host
may produce cLntibacterial ntibodies. CR correlates inversely with the number of different
biotypes of Enterohacteriaceae isolated from faecal samples. In chapter 2 the natural
variation in the nun'rber of different biotypes of Entct'obacteriaceue per faecal sample was
assessed in healthy individuals. It followed that reliable determination of the mean number
of diffèrent biotypes, the inverse of which is representative for the CR of zur individual,
required study of fbur faecal samples of this individual. In chapter 4 this way of rneasuring
CR in humirns was coÍnpared with the golden standard for measuring CR: 10 healthy
individuals were contaminated orally with a neomycin resistant E.r:o/l (NR-E.coll) strain and
the faecal concentration of this strain was measured during l4 days after the contirmination.
this faecal concentration being the measure for the CR. Both rnethods for CR were
correlated significantly (P<0.01 ).
The second tool is irrununor.norphometry. Inununomorphometry combines irnage analysis
and indirect intmunofluorescence. The antibacterial antibodies thus measured are a direct
consequence of the interaction between the host and his microflora. First of all we showed
in chapter 3 that it is possible to measure titres of urtibodies directed against pure cultures
of Enterobacteriaceae by combining classical indirect immunofluorescence (IIF) with
reading of the IIF slides by an image processing system. Reading of IIF titres by the image
processing system was nrore accurate tir iur eye reading. With this nlethod serum antibody
titres against the NR-E.coll strain, used for oral contiunination in chapter 4, were measured.
Persons who elirninated the NR-E.coli strain fastest fronr their intestinal tract didnot produce
highest antibody titres against ttre NR-E.c'oii strain. On the contriuy, the longer the NR-
E.coli slrain remained in the digestive tract the higher the antibody titres against the NR-
E.coli. Therefbre. elimination of an oral contaminant fiom the intestines is not IgG or IgM
antibody mediated.
Faecal bacteria can be divided in morphologically different groups by image analysis.
Combined with the IIF technique it results in immunornorphometry described in chapter -5,
100
8. Summary
which enables detennination of plasma antibody titres of IgA. IgG and IgM isotype against
morphologically defined groups (morphotypes) of faecal bacteria in healthy irrdividuals.
Each individual has his own pattern of antibacterial antibodies.
Immunomorphonretry can be applied to study specificit ies of the serurn antibodies against
faecal bacteria. In chapter 6 it was shown that healthy individuuls not only possess
antibodies against l"reir own autochthonous intestinal bacteria, but they also have antibodies
of both the IgA, IgG and IgM isotype against allogenous faecal bacteria. These antibodies
were left in their sera after removal of the antibodies against the autochthonous faecal
bacteria by absorption. Relatively more IgA antibodies appeared to be directed against
allogenous than against autochthonous faecal bacteria, indicating that the autochthonous
microflora is less immunogenic than the allogenous microflora or that tolerance exists
towards the autochthonous nricroflora. If a person has many antibodies of IgA and IgG
isotype against his own microflora, this could mean that his indigenous microflora is not
very stable. This could indicate that he could have had the chance of rnounting a specific
humoral immune response against malv species of allogenous anaerobic intestinal bacteria.
resulting in antibodies of IgA and IgG isotype against a wide range of allogenous intestinal
bacteria. Indeed we found that persons who reacted with specific untibodies to many
bacteria of their own microflora, also tended to react specifically to bacteria in tbe
allogenous microflora of the other healthy volunteers.
Both tools described above were used in our study on the possible role of the indigenous
intestintrl microflora in SLE. in chapter 7. The CR of the indigenous intestina.l rnicroflora
tended to be lower in SLE patients than in healthy individuals. Quantitative diÍterences in
the humori-rl esponse to indigenous intestinal bacteria were found between SLE patients and
healthy individuals. IgM titres were found to be lower both in patients with active and
inactive SLE as compared to healthy individuals. Specific (IgG) antibacterial ;urtibody
responses were increased in the group with inactive SLE. However, in the group with active
SLE a much lower titre of IgG antibacterial antibody titres was found, aithough the
concentration of total plasma IgG was almost doubled in cornparison with the
concentrations in the group with inactive SLE.
These results could indicate that in SLE patients more different bacteria rnay translocate
across the gut wall due to a lower CR. Some of these bactelia may serve as turtigen for the
production of iLnti-bacterial iurtibodies crossreacting with DNA. IgM rurtibacterial ntibody
titres were decreased in patients with SLE indicating a ftri l ing network. As a result of this
failing network and possibly of a lower CR, IgG antibacterial antibodies were increased in
patients with inactive SLE. However, the production of IgG anti-bacterial antibodies was
decreased in patients with active SLE. This could be in fervour of increased. possibly
antigen driven, production of those antibodies that play a role in exacerbations of SLE, or
might be explained by usage of these IgG antibodies in immune complexes. The latter
101
Aspects of the host-mícroflora inter(k:tk)n
explation could point at a role of the antibacterial antibodies in the etiology of part of the
exacerbations of human SLE.
t02


Aspects of the host-microflora interaction and its possible impact on auto-immune disease

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