Showing posts with label IgG. Show all posts
Showing posts with label IgG. Show all posts

8.7.11

How are low mannin-binding lectin (MBL) significant in Crohn's?

"Low Mannan-binding lectin serum levels are associated with complicated Crohn's disease and reactivity to oligomannan (ASCA)." in American Journal of Gastroenterology (2009)
"CONCLUSIONS: Low or deficient MBL serum levels are significantly associated with complicated (stricturing and penetrating) CD phenotypes but are negatively associated with the non-stricturing, non-penetrating group. Furthermore, CD patients with low or deficient MBL are significantly more often ASCA positive, possibly reflecting delayed clearance of oligomannan-containing microorganisms by the innate immune system in the absence of MBL."

"Abstract 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."
"Full article:  In conclusion, we were able to demonstrate that ASCA-positive patients had significantly more immune reactivities to mycobacterial antigens. In a subgroup of ASCA-positive CD patients, anti-mycobacterial immunoglobulins at least partially represent cross-reactive ASCA, while in others there seem to be separate ASCA and anti-mycobacterial antibodies that do not cross-react. Furthermore, purified anti-M smegmatis IgG showed low or no binding to yeast mannan. Therefore, we postulate that our results reflect more the predisposition of CD patients to develop increased immune reactivities to various ubiquitous antigens in general and mannosylated antigens in particular, rather than a role of mycobacteria in the induction of ASCA."

"Mannan-binding lectin deficiency results in unusual antibody production and excessive experimental colitis in response to mannose-expressing mild gut pathogens"
"Conclusions: These results suggest that systemic MBL helps to prevent excessive inflammation upon access of normally mild pathogens across the damaged intestinal epithelium. Lack of this innate defence promotes antibody responses with cross-reactive potential against common mannan epitopes. These interpretations are compatible with the increased prevalence of ASCA and complicated disease phenotypes in MBL-deficient patients with CD."

"Deficiency for mannan-binding lectin is associated with antibodies to Saccharomyces cerevisiae in patients with Crohn’s disease and their relatives" in Gut (2007)
"Therefore, our paper provides further evidence that genetically altered MBL levels in patients with Crohn’s disease and their relatives could be, at least partly, responsible for the enhanced  immune reactivity to yeast antigens seen in a subgroup of these patients and their relatives.  However, other factors also contribute to the development of this unusual immune reaction, as there are MBL-deficient healthy people who are ASCA negative."

c.f. "Mannan binding lectin (MBL) gene polymorphisms are not associated with anti-Saccharomyces cerevisiae (ASCA) in patients with Crohn’s disease" in Gut (2006)
"We found no association between the presence of ASCA and polymorphisms/mutations in the MBL gene in a large cohort of CD patients and conclude that the occurrence of ASCA is not related to MBL polymorphisms/mutations. This is in contrast with a previous report in which such an association was suggested. Therefore, we consider the relationship between ASCA and MBL highly controversial."

13.6.11

What is the difference between IgE and IgG mediated allergies and is it significant?

IgE
IgG

The difference is significant because in some studies Crohn's patients have not demonstrated IgE allergies while showing significant IgG mediated allergies.  Testing with IgE (skin), therefore, does not eliminate the possibility of food-based allergies.
See "Gut mucosal response to food antigens in Crohn's disease" in Alimentary Pharmacology and Therapeutics (2002)
"The role of food-specific IgE has also been examined in a study of sera from Crohn's disease patients, healthy controls and allergic subjects. IgE binding to food antigens (yeast, corn, celeriac, wheat) was assessed by an immunodot assay.27 Levels of IgE/IgG anti-IgE immune complexes were determined. In Crohn's disease sera, no food-specific IgE could be detected, but levels of immune complexes of IgE and IgG anti-IgE autoantibodies were significantly increased compared to healthy controls. pH treatment of purified IgE/IgG anti-IgE immune complexes resulted in a significant increase in specific IgE to yeast, corn, wheat and celeriac, detected by radioallergosorbent test, only in the serum sample purified from allergic subjects. After pH treatment of Crohn's disease immune complexes, specific IgE levels still remained very low. Thus, even if IgE seems to represent an autoantigen in Crohn's disease, it is unlikely to specifically participate in the pathophysiology of the putative food adverse reactions." [emphasis mine]

Do food allergies worsen Crohn's symptoms?

Crohn's and Colitis Foundation of America, Diet and Nutrition
"Is IBD caused by allergy to food?
No. Although some people do have allergic reactions to certain foods, neither Crohn's disease nor ulcerative colitis is related to food allergy. People with IBD may think they are allergic to foods because they associate the symptoms of IBD with eating."

"Immune sensitization to food, yeast and bacteria in Crohn’s disease" in Alimentary Pharmacology and Therapeutics (2001) [full article]
Discussion: "This study has demonstrated a marked sensitization to a broad range of food, bacterial and yeast antigens in patients with Crohn’s disease.
... Disease distribution, disease activity and the use of drug therapy, did not appear to influence the patients’ lymphocyte responses to the antigens tested.
... Whether the lymphocyte sensitization to lumenal antigens in Crohn’s disease is due to breached epithelium or is a part of the pathogenic process in some other way, such as a general immune cell hyper-responsiveness, is unknown.
... Crohn’s disease patients demonstrated abnormal rectal blood flow responses to yeast and citrus fruits, when group data were analysed."
Conclusions: "... These sensitized lymphocytes may contribute to the inflammatory process."

"Gut mucosal response to food antigens in Crohn's disease" in Alimentary Pharmacology and Therapeutics (2002) [full article]
"This study has shown that patients with Crohn's disease have a markedly increased response to food antigens, demonstrated both in vivo and in vitro, compared with healthy subjects. Markedly increased responses were observed to all the food antigens tested in the Crohn's disease patients, although the particularly stringent statistical criteria which were applied suggested that the most significant responses occurred to yeast and citrus fruits. ...
Whether the immunological and vascular changes observed are primary or secondary events in the pathogenesis of Crohn's disease remains to be determined. The responses obtained in patients with Crohn's disease may be secondary to sensitization that has occurred due to the breached gut epithelium, although substantial evidence suggests that antibody responses do not occur in other conditions in which the epithelium is breached, such as ulcerative colitis. If related to breached epithelium, the response may result from a genetically determined susceptibility.
... Even if these are secondary events, the dramatic in vivo changes in blood flow support the possibility that this sensitization is of clinical relevance. These data, together with the clinical response to purified liquid diets, provide strong evidence for a pivotal role in the ongoing inflammation which characterizes this disease.
... Given that food exposure is greatest in the proximal gut, it might be that disease is more common in the distal small bowel and colon. We do not believe that exposure to food antigens is the primary abnormality in Crohn's disease. However, exposure to food in the proximal gut may lead to immune sensitization, as demonstrated by several techniques in this study, resulting in activation of immune cells which circulate and re-home to where they are most concentrated (the ileum), with resultant mucosal inflammation.
... Although the strongest data were obtained for a response to citrus fruit and yeast antigens, the individual data supported the possibility of an abnormal response to the full range of antigen groups tested. In an individual, any one or more of these protein groups may be important.
... In a study of patients with Crohn's disease, ulcerative colitis, other miscellaneous diarrhoeal illnesses and healthy controls, the presence of ASCA was strongly associated with Crohn's disease, in particular small bowel disease. ... IgG and IgA ASCA were significantly raised in Crohn's disease, especially in the presence of small bowel disease.
... The specificity of the antibody response in Crohn's disease to S. cerevisiae, but not to Candida albicans, further supports the concept that ASCA are not simply the result of a generalized increase in intestinal permeability.
... Levels of IgE/IgG anti-IgE immune complexes were determined. In Crohn's disease sera, no food-specific IgE could be detected, but levels of immune complexes of IgE and IgG anti-IgE autoantibodies were significantly increased compared to healthy controls.
... If sensitized lymphocytes and specific antibodies play a pathogenic role, the exclusion of relevant foods may provide therapeutic benefit, even in the short term.
...  there were no differences between patients and controls in skin antigen testing. This finding is in agreement with other reports of the failure of skin testing to diagnose food sensitivities in patients with suspected food allergies or inflammatory bowel disease.  This difference between skin testing and blood and gut testing also suggests distinct compartmentalization of immune responses, with gut sensitization leading to a specific gut response." [emphases mine]

"What Is the Role of Food Allergy and/or Intolerance in the Genesis of IBD?" in General Gastroenterology (2006)
"True food allergies constitute a different pathogenesis and pathology from true IBD. Although the true cause of IBD remains elusive, it appears to involve a combination of genetic susceptibility, immune dysregulation, and environmental pressures. Patients with IBD are more likely to suffer from food allergies or intolerances than the normal population, but there is not good evidence to suggest that an allergy is the trigger for the underlying inflammatory process. Whereas some groups have been able to demonstrate immune responses to certain food antigens in patients with Crohn's disease, these findings cannot be replicated in other populations, making this mechanism for a pathogenesis unlikely. In patients with subclinical disease, an allergy can precipitate IBD phenotypes, but again, the link between allergies and causation is weak. Certainly those patients who have undiagnosed food intolerances are less likely to respond to standard IBD therapies.
Patients should be counseled regarding their dietary habits to monitor which specific foods or food groups may trigger worse gastrointestinal or systemic symptoms. Elimination diets, however, are rarely needed in the IBD patient."

"Clinical Relevance of IgG Antibodies against Food Antigens in Crohn’s Disease: A Double-Blind Cross-Over Diet Intervention Study" in Digestion (2010)
Results:  "The daily stool frequency significantly decreased by 11% during a specific diet compared with a sham diet. Abdominal pain reduced and general well-being improved. "
Conclusion:  "A nutritional intervention based on circulating IgG antibodies against food antigens showed effects with respect to stool frequency. The mechanisms by which IgG antibodies might contribute to disease activity remain to be elucidated." [emphasis mine]
My 5% better comment:  If 10 trips to the bathroom are the norm, this would be reduced by 1.  If each trip takes on average 15 minutes, this would save approximately 8 hours per month, which is the equivalent of one working day.  Would identifying IgG antigens and eliminating them be meaningful for a CDer?  You bet.

How do food allergies affect the gastro-intestinal system?

"Gastrointestinal Manifestations of Food Allergies in Pediatric Patients" in Nutr Clin Pract (2005) 
"Foods that account for 90% of allergic reactions in children are cow's milk protein, eggs, peanut, soy, tree nuts, fish, and wheat. Food allergy can manifest as urticaria/angioedema, anaphylaxis, atopic dermatitis, respiratory symptoms, or a gastrointestinal (GI) disorder. GI allergic manifestations can be classified as immunoglobulin E (IgE) mediated (immediate GI hypersensitivity and oral allergy syndrome); “mixed” GI allergy syndromes (involving some IgE components and some non-IgE or T-cell-mediated components) include eosinophilic esophagitis and eosinophilic gastroenteritis. Non-IgE-mediated or T-cell-mediated allergic GI disorders include dietary protein enteropathy, protein-induced enterocolitis, and proctitis. All these conditions share a common denominator: the response of the immune system to a specific protein leading to pathologic inflammatory changes in the GI tract. This immunological response can elicit symptoms such as diarrhea, vomiting, dysphagia, constipation, or GI blood loss, symptoms consistent with a GI disorder."

6.6.11

Are some therapies more suitable to the internal-perforating CD subtype?

Positive serologic tests for internal-perforating CD subtype:
from Inflammatory Bowel Disease:  Translating Basic Science into clinical practice, Targon et al., p. 236-7
  • Anti-cBirl flagellin
    • associated with small bowel disease
  • ASCA
    • IgA and IgG Anti-Saccharomyces cerevisiae antibodies
    • associated with small bowel disease
  • IgA Anti-OmpC
    • antibody against outer membrane porin C Escherichea coli

METHODS OF ASSESSING CROHN'S DISEASE PATIENT PHENOTYPE BY 12 SEROLOGIC RESPONSE, patents, Targen
"...[I]nternal perforating disease is a clinical subtype of Crohn's disease defined by current or previous evidence of entero-enteric or entero-vesicular fistulae, intra-abdominal abscesses, or small bowel perforation."

Are some therapies more suited to the fibrostenotic CD subtype?

Positive serologic tests for fibrostenotic CD:
from Inflammatory Bowel Disease:  Translating Basic Science into clinical practice, Targon et al., p. 236
  • Anti-cBirl flagellin
    • associated with small bowel disease
  • ASCA
    • IgA and IgG Anti-Saccharomyces cerevisiae antibodies
    • associated with small bowel disease
  • Anti-I2
    • IgA antibody against Pseudomonas Fluorescens 
    • also significantly more likely to require surgery
METHODS OF ASSESSING CROHN'S DISEASE PATIENT PHENOTYPE BY 12 SEROLOGIC RESPONSE, patents, Targen
"The 'fibrostenotic subtype' of Crohn's disease is a classification of Crohn's disease characterized by one or more accepted characteristics of fibrostenosing disease. Such characteristics of fibrostenosing disease include, for example, documented persistent intestinal obstruction or an intestinal resection for an intestinal obstruction. The fibrostenotic subtype of Crohn's disease can be accompanied by other symptoms such as perforations, abscesses or fistulae, and further can be characterized by persistent symptoms of intestinal blockage such as nausea, vomiting, abdominal distention and inability to eat solid food. Intestinal X-rays of patients with the fibrostenotic subtype of Crohn's disease can show, for example, distention of the bowel before the point of blockage.
The requirement for small bowel surgery in a subject with the fibrostenotic subtype of Crohn's disease can indicate a more aggressive form of this subtype. As shown in Example I, patients expressing IgA anti-I2 antibodies were significantly more likely to have the fibrostenotic subtype of Crohn's disease and significantly more likely to require small bowel surgery than those not expressing IgA anti-I2 antibodies. In addition, the amplitude or level of IgA anti-I2 antibodies in a subject can be correlated with the likelihood of having a particular clinical subtype of Crohn's disease. As shown in Example I, quartile analyses revealed that higher levels of IgA anti-I2 antibodies were more strongly associated with the fibrostenotic subtype of Crohn's disease and small bowel involvement and were negatively associated with ulcerative colitis-like Crohn's disease than were lower levels. Furthermore, the greater the number of fibrostenotic markers that a subject possesses, the greater chance that the subject will have an aggressive form of the fibrostenotic subtype of Crohn's disease requiring small bowel surgery (see Example I). For example, a subject with two or more markers can have a more severe form of the fibrostenotic subtype than a patient with one marker."