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WORLD GASTROENTEROLOGY NEWS JULY 2019
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the presence of autoimmune disease
was found in 19 patients (16.7%),
hypothyroidism was the main diagnosis,
and it was present in 52.6%
of patients compared with 4.2%
in controls. Two patients had more
than one concomitant autoimmune
diseases (one hyperthyroidism/vitiligo
and one hypothyroidism/scleroderma/
rheumatoid arthritis). Most of the
patients with concomitant autoimmune
disease (79%) had the autoimmune
disease established before the
diagnosis of achalasia (median: 14.6
years). For 10.5% of the patients
the autoimmune disease was established
after the diagnosis of achalasia
(median: 2 years) and 10.5% had the
diagnosis occurring simultaneously
for both conditions. Thirteen of the
19 achalasia patients (68.4%) with
autoimmune disease had history of
familial autoimmunity (6 with hypothyroidism,
one with hyperthyroidism,
and 6 with rheumatoid arthritis).
Compared with GERD, the achalasia
group was 3.8-times more likely to
have an autoimmune disease including,
thyroidopathies (RR=3), and
chronic inflammatory disease including
allergic rhinitis, asthma, rosacea
and gout (RR=3.02).10
Human Leukocyte Antigen
Association
Associations between achalasia and
HLA-DQB1*05:03 and HLADQB1*
06:01; HLA-DQA1*01:03;
and HLA-DQB1*03:01 and HLADQB1*
03:04 have been determined.
In fact, many studies have also
shown a positive association with
DQw1, DQA1*0103, DQB1*0601,
DQB1*0602, DQB1*0603,
DQB1*0601, DQB1*0502, and
DQB1*0503 alleles, in Caucasians.
In a study of 1068 cases of achalasia
from central Europe, Spain
and Italy, an 8-residue insertion at
position 227-234 in the cytoplasmic
tail of HLA-DQβ1 (encoded
by HLA-DQB1*05:03 and HLADQB1*
06:01) was characterized as
conferring the strongest risk for achalasia,
and showed a particular geospatial
north-south gradient among
Europeans. The finding of this insertion
being less common in northern
European populations, as compared
with those from the southern regions
mirrored the differential prevalence of
the disease between populations.12 Finally,
the HLA-DRB1*14:54:01 and
DQB1*05:03:01 and the extended
haplotype were characterized as risk
factor for achalasia in mixed-ancestry
Mexican individuals suggesting that
the haplotype was introduced by admixture
with European and/or Asian
populations.13
Immunosuppressive therapies
Finally, there are some reports of
achalasia patients under treatment
with corticosteroids (prednisolone,
methylprednisolone or beclomethasone)
alone or combined with other
immunosuppressive drugs (methotrexate,
azathioprine or cyclophosphamide)
with dramatic clinical
improvement and complete recovery
of peristalsis corroborated by HRM,
lending further credence to the notion
that this disease has an autoimmune
component.14
Conclusion
The initial event that triggers achalasia
may be the result of a repetitive insult
produced by neurotropic virus infection,
likely HSV-1, which induces a
conspicuous and persistent inflammation
at the perineural level, in the
myenteric plexus. Not all infected
patients will develop achalasia, on
account of a genetic predisposition to
develop a chronic auto-inflammatory
response that has the potential to
progress to the disease.
References
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cells in the myenteric plexus of
achalasia patients show a skewed
TCR repertoire and react to HSV-
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Furuzawa-Carballeda J, Torres-Landa
S, Valdovinos MA, et al. New
insights into the pathophysiology
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Furuzawa-Carballeda J, Aguilar-León
D, Gamboa-Domínguez A, et
al. Achalasia--An Autoimmune
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Liu ZQ, Chen WF, Wang Y, et al.
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Im SK, Yeo M, Lee KJ. Proteomic
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Clayton S, Cauble E, Kumar A, et
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BMC Gastroenterol. 2019;19:28.
Furuzawa-Carballeda J, Boon L, Torres
Villalobos G, et al. Gelatinase
B/Matrix Metalloproteinase-9 as
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Bruley des Varannes S, Chevalier J,
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