Genetic variants of the mannan-binding lectin are associated with immune reactivity to mannans in Crohn’s disease

Seibold, Frank; Konrad, Astrid; Flogerzi, Beatrice; Seibold-Schmid, Beatrice; Arni, Stephan; Jüliger, Simone; Kun, Jürgen F. J.

doi:10.1053/j.gastro.2004.07.056

Cited by 59 publications

(54 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

Section: Introductionmentioning

confidence: 99%

“…Antibodies against certain self-antigens, such as tropomyosin, have been detected in some patients with UC [10], while some patients with CD have developed antibodies against mannan, a component of the yeast Saccharomyces cerevisiae cell wall. Enhanced mannan exposure seems to stimulate specific immune responses in a subgroup of CD patients with genetically determined low mannan binding lectin concentrations [11].McCabe et al[12] examined the B-cell repertoire in intestinal mononuclear cells from normal individuals and patients with IBD. They found that while genes from all seven heavy chain variable region (V H ) gene families were expressed, differences in V H usage in lamina propria intestinal B cells exist between CD, UC and normal individuals.…”

mentioning

confidence: 99%

See 1 more Smart Citation

B‐cell clonal diversification and gut‐lymph node trafficking in ulcerative colitis revealed using lineage tree analysis

et al. 2008

View full text Add to dashboard Cite

In studies of inflammatory bowel diseases (IBD), research has so far focused mainly on the role of T cells. Despite evidence suggesting that B cells and the production of autoantibodies may play a significant role in IBD pathogenesis, the role of B cells in gut inflammation has not yet been thoroughly investigated. In the present study we used the new approach of lineage tree analysis for studying immunoglobulin variable region gene diversification in B cells found in the inflamed intestinal tissue of two ulcerative colitis patients as well as B cells from mucosa-associated lymph nodes (LN) in the same patients. Healthy intestinal tissue of three patients with carcinoma of the colon was used as normal control. Lineage tree shapes revealed active immune clonal diversification processes occurring in ulcerative colitis patients, which were quantitatively similar to those in healthy controls. B cells from intestinal tissues and the associated LN are shown here to be clonally related, thus supplying the first direct evidence supporting B-cell trafficking between gut and associated LN in IBD and control tissues. IntroductionUlcerative colitis (UC), one of the idiopathic inflammatory bowel diseases (IBD), is a chronic relapsing inflammatory disorder that may lead to significant impairment of gastrointestinal structure and function. UC usually involves the large intestine and extends proximally from the rectum upwards in a continuous fashion. Histologically, inflammation is usually limited to the mucosal layer and may involve ulceration and crypt abscess formation. UC has also been linked to an increased risk of gastrointestinal malignancy [1].Despite recent progress in IBD research, in human subjects as well as a wide variety of experimental animal models, many questions concerning the immunological and genetic basis of the disease remain unanswered. The mucosa-associated lymphoid 2600tissue of the gastrointestinal tract has the important tasks of, on the one hand, recognizing harmful pathogens and antigens within the gut and mounting an appropriate immune response against them and, on the other hand, knowing when and how to dampen or suppress that response once the assault has been cleared or when commensal flora or self-antigens are encountered [2]. The pathogenesis of IBD appears to be related to a disruption of that finely tuned and regulated balance which exists within the mucosa-associated lymphoid tissue, resulting in deregulated and exaggerated local immune responses. This imbalance is most probably a result of complex genetic, environmental, and immunological susceptibility factors [3].Experimental models of intestinal inflammation indicate that mucosal inflammation is probably mediated either by excessive effector T-cell function or deficient regulatory T-cell function. Exaggerated T helper 1 cell response associated with increased secretion of IL-12, IFN-g and/or TNF results in a Crohn's Disease (CD)-like colitis in these experimental models, and exaggerated T helper 2 cell response associated with increas...

show abstract

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

B‐cell clonal diversification and gut‐lymph node trafficking in ulcerative colitis revealed using lineage tree analysis

et al. 2008

View full text Add to dashboard Cite

show abstract

“…16,18,20 To date, the MBL2*XA, B, C and D variants have been associated with the predisposition and/or severity of various immunodeficiencies, autoimmune and infectious diseases in childhood and adult age (for a review, see Eisen and Minchinton; Kilpatrick 21,22 ). Alternatively, the MBL2*HA diplotype and/or high plasma concentrations of MBL multimers have been associated with protection to some of these diseases, 14,23,24 but to predispose to and/ or to increase the severity of leprosy, tuberculosis, 21,25 visceral leishmaniasis, 26 sporadic ulcerative colitis 27 and rheumatic heart disease. 28 A total of 96% of the variation in the plasma levels of MBL multimers can be explained by genetic polymorphisms.…”

Section: Introductionmentioning

confidence: 99%

Association of a new mannose-binding lectin variant with severe malaria in Gabonese children

et al. 2006

View full text Add to dashboard Cite

Mannose-binding lectin (MBL2) variants that decrease the plasma level of the protein or encode dysfunctional proteins are frequently associated with the severity of a number of infections and autoimmune disorders. The high frequencies of these variants in most populations of the world are probably maintained by some selective advantage against widespread diseases. We found 14 new MBL2 allelic haplotypes, two of them with non-synonymous variants, by screening 136 children with uncomplicated malaria, 131 children with severe malaria and 39 older healthy schoolchildren. We also found a significant association of a novel variant with susceptibility to severe malaria (P ¼ 0.010). Increased MBL plasma levels and corresponding MBL2 genotypes were associated with lower concentration of several cytokines and chemokines in plasma of malaria patients. We suggest that malaria could have been one of the evolutionary driving forces shaping the MBL2 polymorphism in the African population.

show abstract

“…We have previously shown that deficiency for MBL associates with the ASCA-positive subgroup of CD patients [27,28] . Thus, it was of interest, if in CD, deficiency for MBL might associate with elevated levels of anti-mycobacterial IgG as well.…”

Section: Introductionmentioning

confidence: 96%

“…Because in our cohor t of CD patients MBLdeficiency associates with positivity for ASCA [27,28] , we wondered whether generation of anti-mycobacterial antibodies may associate with this deficiency as well, and whether such an association may depend on certain strains with differential presence of the terminal α-1,3 linked mannose motive and/or distinctly capped LAM. Indeed, we found an association of MBL deficiency with the prevalence of anti-mycobacterial antibodies.…”

mentioning

confidence: 99%

Partial overlap of anti-mycobacterial, and anti- Saccharomyces cerevisiae mannan antibodies in Crohn's disease

Müller¹,

Schaffer²,

Schoepfer³

et al. 2008

WJG

Self Cite

View full text Add to dashboard Cite

AIM:To test whether humoral immune reaction a g a i n s t myc o b a c t e r i a m ay p l ay a ro l e i n a n t i - S a c c h a r o my c e s c e r e v i s i a e a n t i b o d i e s ( A S C A )generation in Crohn's disease (CD) and/or whether it correlates with clinical subtypes. M E T H O D S :T h e d o m i n a n t A S C A e p i t o p e w a s ASCA and anti-mycobacterial antibodies were affinity purified to assess cross-reactivities. Anti-mycobacterial IgG were induced by BCG-infection of mice. RESULTS: G N L b o u n d t o d i f f e r e n t e x t e n t s t o mycobacterial lysates, abundantly to purified mannosecapped (Man) LAM from M tuberculosis , but not to uncapped LAM from M smegmatis . Fifteen to 45% of CD patients but only 0%-6% of controls were seropositive against different mycobacterial antigens. Anti-mycobacterial IgG correlated with ASCA (r = 0.37-0.64; P = 0.003-P < 0.001). ASCA-positivity and deficiency for mannan-binding lectin synergistically associated with anti-mycobacterial IgG. In some patients, anti-mycobacterial antibodies represent crossreactive ASCA. Vice-versa, the predominant fraction of ASCA did not cross-react with mycobacteria. Finally, fistulizing disease associated with antibodies against M avium , M smegmatis and MAP (P = 0.024, 0.004 and 0.045, respectively). CONCLUSION: Similar to ASCA, seroreactivity against mycobacteria may define CD patients with complicated disease and a predisposition for immune responses against ubiquitous antigens. While in some patients anti-mycobacterial antibodies strongly cross-react with yeast mannan; these cross-reactive antibodies only represent a minor fraction of total ASCA. Thus, mycobacterial infection unlikely plays a role in ASCA induction.

show abstract

Genetic variants of the mannan-binding lectin are associated with immune reactivity to mannans in Crohn’s disease

Cited by 59 publications

References 23 publications

B‐cell clonal diversification and gut‐lymph node trafficking in ulcerative colitis revealed using lineage tree analysis

B‐cell clonal diversification and gut‐lymph node trafficking in ulcerative colitis revealed using lineage tree analysis

Association of a new mannose-binding lectin variant with severe malaria in Gabonese children

Partial overlap of anti-mycobacterial, and anti- Saccharomyces cerevisiae mannan antibodies in Crohn's disease

Contact Info

Product

Resources

About