A deficiency of interstitial cells of Cajal in Chagasic megacolon

Hagger, R; Finlayson, Caroline; Kahn, Fiona; Oliveira, Ricardo Brandt de; Chimelli, Leila; Kumar, Devinder

doi:10.1016/s0165-1838(00)00076-x

Cited by 64 publications

(45 citation statements)

References 13 publications

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“…Bassotti and Villanacci [1] claim that the hypotheses we proposed (inclusion of mast cells and heterogeneous distribution of ICC in different regions of the colon) are unfounded. We have no other explanations for the discrepancies between our study, which identified increasing numbers of intramuscular ICC only, and other studies [2][3][4], which found a reduction of ICC in all layers evaluated.…”

Section: To the Editorcontrasting

confidence: 99%

“…In response to the considerations contained in the letter of Bassotti and Villanacci [1], we would like to emphasize that in our study [2] we identified a reduced number of interstitial cells of Cajal (ICC) in chagasic megacolon (CM), as had been previously reported in studies by Hagger et al [3] and Geraldino et al [4]. Hypotheses were raised trying to explain the discrepancy with the results published by Iantorno et al [5].…”

Section: To the Editorsupporting

confidence: 67%

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The development of chagasic megacolon requires severe denervation and the reduction in interstitial cells of Cajal number might be a contributing factor

2012

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Bassotti and Villanacci [1], we would like to emphasize that in our study [2] we identified a reduced number of interstitial cells of Cajal (ICC) in chagasic megacolon (CM), as had been previously reported in studies by Hagger et al. [3] and Geraldino et al. [4]. Hypotheses were raised trying to explain the discrepancy with the results published by Iantorno et al. [5]. Bassotti and Villanacci [1] claim that the hypotheses we proposed (inclusion of mast cells and heterogeneous distribution of ICC in different regions of the colon) are unfounded. We have no other explanations for the discrepancies between our study, which identified increasing numbers of intramuscular ICC only, and other studies [2-4], which found a reduction of ICC in all layers evaluated.Bassotti and Villanacci [1] state that we did not distinguish between well-established colonic populations of ICC. However, we did describe in our paper [2] that we counted ICC at the level of the myenteric plexus (intermuscular space between circular and longitudinal muscle layers) and from ICC in circular muscle layer separately. We did not count ICC in the submucosa nor in longitudinal muscle layers.However, we fully agree with Bassotti and Villanacci [1] that it is necessary to evaluate ICC and glial cells in conjunction with the study of enteric neurons, as our findings support the hypothesis that the development of CM requires severe denervation and the reduction in ICC number is, in part, a consequence of denervation and that this might contribute to the pathophysiology of CM.

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Section: To the Editorcontrasting

confidence: 99%

Section: To the Editorsupporting

confidence: 67%

The development of chagasic megacolon requires severe denervation and the reduction in interstitial cells of Cajal number might be a contributing factor

2012

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“…The strength of this study relies in the fact that the authors took into consideration patients without overt megacolon and the cell count was carried out in complete intestinal rings that allowed them to correct the neuron and ICC dispersion due to intestinal dilation and muscular hypertrophy of the megacolon. The findings of ICC decrease were consistent with previous studies in chagasic patients with megacolon [2][3][4]. However, in our study, we found an increase of one of the three colonic populations of ICC, the intramuscular, and we disagree with the interpretation of Adad et al that this increase might have been due to an inclusion of mast cells in the count, since these were specifically excluded, as specified in the paper [4]; on the other hand, in our experience the distribution of ICC within the human colon is fairly homogeneous (Bassotti and Villanacci, unpublished observations).…”

supporting

confidence: 92%

The pathophysiology of chagasic megacolon: beyond ICC…

Bassotti

Villanacci

2012

Virchows Arch

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To the editor: Dear Sir, We read with interest the recent article by Adad et al. [1] in which they reported a reduction of the number of interstitial cells of Cajal (ICC) in the colonic myenteric plexus and circular muscle areas of chagasic patients with or without megacolon. This reduction was much more pronounced in patients with megacolon, where it was also accompanied by a significant decrease of enteric neurons [1]. The strength of this study relies in the fact that the authors took into consideration patients without overt megacolon and the cell count was carried out in complete intestinal rings that allowed them to correct the neuron and ICC dispersion due to intestinal dilation and muscular hypertrophy of the megacolon. The findings of ICC decrease were consistent with previous studies in chagasic patients with megacolon [2][3][4]. However, in our study, we found an increase of one of the three colonic populations of ICC, the intramuscular, and we disagree with the interpretation of Adad et al. that this increase might have been due to an inclusion of mast cells in the count, since these were specifically excluded, as specified in the paper [4]; on the other hand, in our experience the distribution of ICC within the human colon is fairly homogeneous (Bassotti and Villanacci, unpublished observations). More importantly, in their paper Adad et al. did not distinguish between the three well established populations of colonic ICC, i.e., ICC submucous (along the submucosal surface of the circular muscle bundle), ICC myenteric (within the intermuscular space between circular and longitudinal muscle layers, myenteric region, which displays the highest yield of ICC in normal tissue), and ICC intramuscular (within the muscle fibers of the circular and longitudinal muscle layers) [4]. This fact might have led to a decreased cell count due to a different methodologic approach.However, we were pleased that Adad et al. did not limit their approach only to ICC, but included enteric neurons, that were also decreased. This fact, in addition to the significant decrease of enteric glial cells we also found in patients with megacolon and other conditions characterized by constipation [4,5] strongly suggests that the development of megacolon requires enteric denervation and that an ICC decrease is an ancillary finding to neurogliopathic abnormalities. References

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“…Damage to the enteric nervous system is an established feature of chagasic GI disorders, and is characterised by neuronal degeneration and loss, connective tissue fibrosis, inflammatory cell infiltration, decreased numbers of interstial cells of Cajal and decreased enteric glia (Koberle 1968;Hagger et al 2000;Iantorno et al 2007). The production of autoantibodies in Chagas' disease has previously been attributed to molecular mimicry, where a cross-reactive immune response to a parasitic epitope and native antigen occurs, or due to a secondary immune response to tissue damage where 'cryptic' antigens which are normally hidden from the immune system are revealed (Kierszenbaum 2005).…”

Section: Significance and Interpretationsmentioning

confidence: 99%

The role of humoral autoimmunity in gastrointestinal neuromuscular diseases

Hubball

Martin

Lang

et al. 2009

Progress in Neurobiology

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Dysfunction of the gastrointestinal neuromuscular apparatus (including interstitial cells ofCajal) is presumed to underlie a heterogeneous group of disorders collectively termed gastrointestinal neuromuscular diseases (GINMDs). Humoral (antibody)-mediated autoimmunity directed against ligand-or voltage-gated ion channels or associated proteins involved in neuromuscular transmission is associated with several acquired neuromuscular diseases of the periphery and is now implicated in an increasing number of less well-characterised diseases. Anti-channel antibodies have been reported in small numbers of patients with GINMD, particularly in those with GI dysfunction secondary to an underlying disease such as neoplasia or infection. However, little is known of humoral autoimmunity in primary GINMDs.This thesis investigated the association between anti-channel antibodies and GINMD, and the human GI tract as a potential target of anti-channel antibodies. The presence of antivoltage-and ligand-gated antibodies was investigated in the serum of patients with primary achalasia, enteric dysmotility and intestinal pseudo-obstruction, and in those with GINMD secondary to Chagas' disease. The functional effect of sera from some of these patients on colonic smooth muscle contractility was also characterised. Finally, the distribution of six voltage-gated potassium channels (VGKCs), which serve essential roles in the peripheral and central nervous systems and are known targets of pathological autoantibodies, were investigated in all layers of the human GI tract.Our findings suggest that currently recognised anti-channel antibodies are not a common pathogenic factor in primary GINMDs. Anti-channel antibodies, in particular anti-VGKC antibodies, were however found in a significant number of individuals with Chagas' disease. Furthermore, circulating factors in patients with chagasic GI disease altered GI smooth muscle contractility in vitro which may have pathological relevance to GI

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A deficiency of interstitial cells of Cajal in Chagasic megacolon

Cited by 64 publications

References 13 publications

The development of chagasic megacolon requires severe denervation and the reduction in interstitial cells of Cajal number might be a contributing factor

The development of chagasic megacolon requires severe denervation and the reduction in interstitial cells of Cajal number might be a contributing factor

The pathophysiology of chagasic megacolon: beyond ICC…

The role of humoral autoimmunity in gastrointestinal neuromuscular diseases

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