Peculiar antibody reactivity to human connexin 37 and its microbial mimics in patients with Crohn's disease

Andreas Koutsoumpas; Dimitrios Polymeros; Zacharias Tsiamoulos; Daniel Smyk; George Karamanolis; Konstantinos Triantafyllou; E. I. Rigopoulou; Alastair Forbes; Diego Vergani; Dimitrios P. Bogdanos; Spiros D. Ladas

doi:10.1016/j.crohns.2010.10.009

Peculiar antibody reactivity to human connexin 37 and its microbial mimics in patients with Crohn's disease

Andreas Koutsoumpas, Dimitrios Polymeros, Zacharias Tsiamoulos, Daniel Smyk, George Karamanolis, Konstantinos Triantafyllou, E. I. Rigopoulou, Alastair Forbes, Diego Vergani, Dimitrios P. Bogdanos, Spiros D. Ladas

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

19 Citations (Scopus)

Abstract

Background/aims: We found that pooled Crohn's disease (CD) sera strongly react with a human gap-junction connexin 37 (Cx37) peptide and tested for anti-Cx37 antibody reactivity in sera from CD patients and controls. We also investigated whether peptide-recognition is due to Cx37/microbial molecular mimicry. Methods: The PSI-BLAST program was used for Cx37(121-135)/microbial alignment. Reactivity to biotinylated human Cx37(121-135) and its microbial mimics was determined by ELISA using sera from 4,4 CD, 30 ulcerative colitis and 28 healthy individuals. Results: Anti-Cx37(121-135) reactivity (1/200 dilution) was present in 30/44 (68%) CD cases and persisted at 1/1000 dilution. Database search shows that Cx37(121-135) contains the -ALTAV- motif which is cross-recognized by diabetes-specific phogrin and enteroviral immunity. Testing of 9 Cx37(121-135)-microbial mimics revealed 57-68% reactivity against human enterovirus C, Lactococcus lactis, coxsackie virus A24 and B4. Anti-Cx37(121-135) was inhibited by itself or the microbial mimics. No reactivity was found against the poliovirus, rubella, and Mycobacterium tuberculosis mimics, or the beta cell phogrin autoantigen. Microbial/Cx37 reactivity was not able to differentiate CD patients from UC or healthy controls, in terms of overall prevalence and antibody titres, but microbial mimics were unable to inhibit reactivity to human Cx37 in the majority of the controls. Conclusions: Sera from CD patients react with connexin 37 and cross-react with specific Cx37-mimicking enteroviral peptides. Microbial/self reactivity can be seen in UC and healthy controls. The lack of responses to other Cx37(121-135) microbial mimics and the inability of the reactive microbes to inhibit reactivity to self is intriguing and warrants further investigation. (C) 2010 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Original language	English
Pages (from-to)	101 - 109
Number of pages	9
Journal	Journal Of Crohns & Colitis
Volume	5
Issue number	2
DOIs	https://doi.org/10.1016/j.crohns.2010.10.009
Publication status	Published - Apr 2011

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10.1016/j.crohns.2010.10.009

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Koutsoumpas, A., Polymeros, D., Tsiamoulos, Z., Smyk, D., Karamanolis, G., Triantafyllou, K., Rigopoulou, E. I., Forbes, A., Vergani, D., Bogdanos, D. P., & Ladas, S. D. (2011). Peculiar antibody reactivity to human connexin 37 and its microbial mimics in patients with Crohn's disease. Journal Of Crohns & Colitis, 5(2), 101 - 109. https://doi.org/10.1016/j.crohns.2010.10.009

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title = "Peculiar antibody reactivity to human connexin 37 and its microbial mimics in patients with Crohn's disease",

abstract = "Background/aims: We found that pooled Crohn's disease (CD) sera strongly react with a human gap-junction connexin 37 (Cx37) peptide and tested for anti-Cx37 antibody reactivity in sera from CD patients and controls. We also investigated whether peptide-recognition is due to Cx37/microbial molecular mimicry. Methods: The PSI-BLAST program was used for Cx37(121-135)/microbial alignment. Reactivity to biotinylated human Cx37(121-135) and its microbial mimics was determined by ELISA using sera from 4,4 CD, 30 ulcerative colitis and 28 healthy individuals. Results: Anti-Cx37(121-135) reactivity (1/200 dilution) was present in 30/44 (68%) CD cases and persisted at 1/1000 dilution. Database search shows that Cx37(121-135) contains the -ALTAV- motif which is cross-recognized by diabetes-specific phogrin and enteroviral immunity. Testing of 9 Cx37(121-135)-microbial mimics revealed 57-68% reactivity against human enterovirus C, Lactococcus lactis, coxsackie virus A24 and B4. Anti-Cx37(121-135) was inhibited by itself or the microbial mimics. No reactivity was found against the poliovirus, rubella, and Mycobacterium tuberculosis mimics, or the beta cell phogrin autoantigen. Microbial/Cx37 reactivity was not able to differentiate CD patients from UC or healthy controls, in terms of overall prevalence and antibody titres, but microbial mimics were unable to inhibit reactivity to human Cx37 in the majority of the controls. Conclusions: Sera from CD patients react with connexin 37 and cross-react with specific Cx37-mimicking enteroviral peptides. Microbial/self reactivity can be seen in UC and healthy controls. The lack of responses to other Cx37(121-135) microbial mimics and the inability of the reactive microbes to inhibit reactivity to self is intriguing and warrants further investigation. (C) 2010 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.",

author = "Andreas Koutsoumpas and Dimitrios Polymeros and Zacharias Tsiamoulos and Daniel Smyk and George Karamanolis and Konstantinos Triantafyllou and Rigopoulou, {E. I.} and Alastair Forbes and Diego Vergani and Bogdanos, {Dimitrios P.} and Ladas, {Spiros D.}",

year = "2011",

month = apr,

doi = "10.1016/j.crohns.2010.10.009",

language = "English",

volume = "5",

pages = "101 -- 109",

journal = "Journal Of Crohns & Colitis",

issn = "1876-4479",

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Koutsoumpas, A, Polymeros, D, Tsiamoulos, Z, Smyk, D, Karamanolis, G, Triantafyllou, K, Rigopoulou, EI, Forbes, A, Vergani, D , Bogdanos, DP & Ladas, SD 2011, 'Peculiar antibody reactivity to human connexin 37 and its microbial mimics in patients with Crohn's disease', Journal Of Crohns & Colitis, vol. 5, no. 2, pp. 101 - 109. https://doi.org/10.1016/j.crohns.2010.10.009

TY - JOUR

T1 - Peculiar antibody reactivity to human connexin 37 and its microbial mimics in patients with Crohn's disease

AU - Koutsoumpas, Andreas

AU - Polymeros, Dimitrios

AU - Tsiamoulos, Zacharias

AU - Smyk, Daniel

AU - Karamanolis, George

AU - Triantafyllou, Konstantinos

AU - Rigopoulou, E. I.

AU - Forbes, Alastair

AU - Vergani, Diego

AU - Bogdanos, Dimitrios P.

AU - Ladas, Spiros D.

PY - 2011/4

Y1 - 2011/4

N2 - Background/aims: We found that pooled Crohn's disease (CD) sera strongly react with a human gap-junction connexin 37 (Cx37) peptide and tested for anti-Cx37 antibody reactivity in sera from CD patients and controls. We also investigated whether peptide-recognition is due to Cx37/microbial molecular mimicry. Methods: The PSI-BLAST program was used for Cx37(121-135)/microbial alignment. Reactivity to biotinylated human Cx37(121-135) and its microbial mimics was determined by ELISA using sera from 4,4 CD, 30 ulcerative colitis and 28 healthy individuals. Results: Anti-Cx37(121-135) reactivity (1/200 dilution) was present in 30/44 (68%) CD cases and persisted at 1/1000 dilution. Database search shows that Cx37(121-135) contains the -ALTAV- motif which is cross-recognized by diabetes-specific phogrin and enteroviral immunity. Testing of 9 Cx37(121-135)-microbial mimics revealed 57-68% reactivity against human enterovirus C, Lactococcus lactis, coxsackie virus A24 and B4. Anti-Cx37(121-135) was inhibited by itself or the microbial mimics. No reactivity was found against the poliovirus, rubella, and Mycobacterium tuberculosis mimics, or the beta cell phogrin autoantigen. Microbial/Cx37 reactivity was not able to differentiate CD patients from UC or healthy controls, in terms of overall prevalence and antibody titres, but microbial mimics were unable to inhibit reactivity to human Cx37 in the majority of the controls. Conclusions: Sera from CD patients react with connexin 37 and cross-react with specific Cx37-mimicking enteroviral peptides. Microbial/self reactivity can be seen in UC and healthy controls. The lack of responses to other Cx37(121-135) microbial mimics and the inability of the reactive microbes to inhibit reactivity to self is intriguing and warrants further investigation. (C) 2010 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

AB - Background/aims: We found that pooled Crohn's disease (CD) sera strongly react with a human gap-junction connexin 37 (Cx37) peptide and tested for anti-Cx37 antibody reactivity in sera from CD patients and controls. We also investigated whether peptide-recognition is due to Cx37/microbial molecular mimicry. Methods: The PSI-BLAST program was used for Cx37(121-135)/microbial alignment. Reactivity to biotinylated human Cx37(121-135) and its microbial mimics was determined by ELISA using sera from 4,4 CD, 30 ulcerative colitis and 28 healthy individuals. Results: Anti-Cx37(121-135) reactivity (1/200 dilution) was present in 30/44 (68%) CD cases and persisted at 1/1000 dilution. Database search shows that Cx37(121-135) contains the -ALTAV- motif which is cross-recognized by diabetes-specific phogrin and enteroviral immunity. Testing of 9 Cx37(121-135)-microbial mimics revealed 57-68% reactivity against human enterovirus C, Lactococcus lactis, coxsackie virus A24 and B4. Anti-Cx37(121-135) was inhibited by itself or the microbial mimics. No reactivity was found against the poliovirus, rubella, and Mycobacterium tuberculosis mimics, or the beta cell phogrin autoantigen. Microbial/Cx37 reactivity was not able to differentiate CD patients from UC or healthy controls, in terms of overall prevalence and antibody titres, but microbial mimics were unable to inhibit reactivity to human Cx37 in the majority of the controls. Conclusions: Sera from CD patients react with connexin 37 and cross-react with specific Cx37-mimicking enteroviral peptides. Microbial/self reactivity can be seen in UC and healthy controls. The lack of responses to other Cx37(121-135) microbial mimics and the inability of the reactive microbes to inhibit reactivity to self is intriguing and warrants further investigation. (C) 2010 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

U2 - 10.1016/j.crohns.2010.10.009

DO - 10.1016/j.crohns.2010.10.009

M3 - Article

SN - 1876-4479

VL - 5

SP - 101

EP - 109

JO - Journal Of Crohns & Colitis

JF - Journal Of Crohns & Colitis

IS - 2

ER -

Peculiar antibody reactivity to human connexin 37 and its microbial mimics in patients with Crohn's disease

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