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Hunter and Brayne Journal of Negative Results in BioMedicine  (2017) 16:8 
DOI 10.1186/s12952-017-0073-4ERRATUM Open AccessErratum to: Do anti-amyloid beta protein
antibody cross reactivities confound
Alzheimer disease research?
Sally Hunter* and Carol BrayneErratum
After publication of the original article [1], it came to the
authors’ attention that evidence relating to the epitopes
recognised and cross reactivities of the antibodies that
form the parents of Bapineuzumab and Solanezumab was
omitted from Table 1.
An updated version of Table 1 is published in this
erratum, with the inclusion of three new references [12–14].
This evidence do not in any way undermine the
argument that the cross-reactivities of anti-amyloid
antibodies may confound research, and in fact can be
interpreted as strengthening the argument.
The cross-reactivity of both Bapineuzumab and
Solanezumab with various Aβ C-terminals and the
cross reactivity of Solanezumab with various plasma
proteins does not clarify the understanding of the APP
proteolytic system and its role in disease, or identify
with any certainty which peptides are of interest and
are being targeted.References
1. Hunter S, Brayne C. Do anti-amyloid beta protein antibody cross reactivities
confound Alzheimer disease research? J Negat Results Biomed. 2017;16:1.
doi:10.1186/s12952-017-0066-3.
2. Thal DR, Schultz C, Dehghani F, Yamaguchi H, Braak H, Braak E. Amyloid
beta-protein (Abeta)-containing astrocytes are located preferentially near N-
terminal-truncated Abeta deposits in the human entorhinal cortex. Acta
Neuropathol. 2000;100:608–17.
3. Hatami A, Monjazeb S, Glabe C. The Anti-Amyloid-beta Monoclonal
Antibody 4G8 Recognizes a Generic Sequence-Independent Epitope
Associated with alpha-Synuclein and Islet Amyloid Polypeptide Amyloid
Fibrils. J Alzheimers Dis. 2015;50:517–25.
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antibodies against Abeta42 fibrils distinguish multiple aggregation state
polymorphisms in vitro and in Alzheimer disease brain. J Biol Chem. 2014;
289:32131–43.* Correspondence: seh66@medschl.cam.ac.uk
Department of Public Health and Primary Care, Institute of Public Health
Forvie Site, University of Cambridge School of Clinical Medicine, Box 113
Cambridge Biomedical Campus, Cambridge CB2 0SP, UK
© The Author(s). 2017 Open Access This artic
International License (http://creativecommons
reproduction in any medium, provided you g
the Creative Commons license, and indicate if
(http://creativecommons.org/publicdomain/ze5. Moore S, Evans LD, Andersson T, Portelius E, Smith J, Dias TB, et al. APP
metabolism regulates tau proteostasis in human cerebral cortex neurons.
Cell Rep. 2015;11:689–96.
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Neurol. 1999;58:210–6.
7. Iwatsubo T, Odaka A, Suzuki N, Mizusawa H, Nukina N, Ihara Y. Visualization
of A beta 42(43) and A beta 40 in senile plaques with end-specific A beta
monoclonals: evidence that an initially deposited species is A beta 42(43).
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8. Citron M, Diehl TS, Gordon G, Biere AL, Seubert P, Selkoe DJ. Evidence that
the 42- and 40-amino acid forms of amyloid beta protein are generated
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Proc Natl Acad Sci U S A. 1996;93:13170–5.
9. Iwatsubo T, Saido TC, Mann DM, Lee VM, Trojanowski JQ. Full-length amyloid-
beta (1-42(43)) and amino-terminally modified and truncated amyloid-beta
42(43) deposit in diffuse plaques. Am J Pathol. 1996;149:1823–30.
10. Saido TC, Yamao-Harigaya W, Iwatsubo T, Kawashima S. Amino- and
carboxyl-terminal heterogeneity of beta-amyloid peptides deposited in
human brain. Neurosci Lett. 1996;215:173–6.
11. Bouter Y, Lopez Noguerola JS, Tucholla P, Crespi GA, Parker MW, Wiltfang J,
et al. Abeta targets of the biosimilar antibodies of Bapineuzumab,
Crenezumab, Solanezumab in comparison to an antibody against
Ntruncated Abeta in sporadic Alzheimer disease cases and mouse models.
Acta Neuropathol. 2015;130:713–29.
12. Miles LA, Crespi GA, Doughty L, Parker MW. Bapineuzumab captures the
N-terminus of the Alzheimer's disease amyloid-beta peptide in a helical
conformation. Sci Rep. 2013;3:1302.
13. Watt AD, Crespi GA, Down RA, Ascher DB, Gunn A, Perez KA, et al. Do
current therapeutic anti-Abeta antibodies for Alzheimer's disease engage
the target? Acta Neuropathol. 2014;127:803–10.
14. Crespi GA, Hermans SJ, Parker MW, Miles LA. Molecular basis for mid-region
amyloid-beta capture by leading Alzheimer's disease immunotherapies. Sci
Rep. 2015;5:9649.le is distributed under the terms of the Creative Commons Attribution 4.0
.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
ive appropriate credit to the original author(s) and the source, provide a link to
changes were made. The Creative Commons Public Domain Dedication waiver
ro/1.0/) applies to the data made available in this article, unless otherwise stated.
Table 1 Epitopes and cross reactivities of selected antibodies raised against Aβ
Antibody Epitope Cross Reactivity Ref
4G8 Raised against synthetic peptide Aβ17-24; epitope
lies within aa 18–23; recognises multiple forms of Aβ
Cross reacts with APP770 and P3; reacts with conformational
epitope of aggregated fibrils including α-synuclein
[2–4]
6E10 Raised against Aβ1-17; epitope lies within aa 4–9;
recognises Aβ with intact N-terminal epitope
Cross reacts with APP and Aβ(1–16); No reaction predicted
with P3
[2, 5]
6F3D Raised against synthetic peptide Aβ8-17; epitope
lies within aa 10–15; recognises Aβ with
intact N-terminal epitope
Predicted to react with Aβ(1–16); Does not react with P3 [2, 6]
MBC40
(Aβ40)
Recognises C-terminal Aβ peptides ending at aa40;
epitope not well described
Cross reacts with N-terminal truncated peptides including P3 [2]
MBC42
(Aβ42)
Recognises C-terminal Aβ peptides ending at aa42;
epitope not well described
Cross reacts with N-terminal truncated peptides including P3 [2]
BS85 Raised against Aβ(25–35); recognises Aβ38, Aβ39, Aβ40,
Aβ42 and Aβ43; epitope not well described
Cross reacts with N-terminal truncated peptides including P3 [2]
BC05 Raised against Aβ(35–43); recognises Aβ42 and Aβ43;
epitope not well described
Cross reacts with N-terminal truncated peptides including P3;
does not recognise Aβ40; used in commercial ELISA kits
for the detection of Aβ42
[7, 8]
BA27 Raised against Aβ(1–40) Recognises Aβ40; 100-1000x
more reactive with Aβ40 than Aβ42 and Aβ43; epitope
not well described
Cross reacts with N-terminal truncated peptides including P3;
used in commercial ELISA kits for the detection of Aβ40
[7]
AβN17
(Leu)
Raised against P3(40); recognises P3(40) and synthetic
P3(42) peptide; epitope not well described
Reactivity with insoluble, aggregated P3(42) not confirmed [7, 9, 10]
3D6 Raised against Aβ with N-terminal aspartic acid; epitope
lies within aa 1–5; recognises multiple C-terminal variations
Does not cross react with sAPPs or full length APP;
No reactivity with N-terminally altered Aβ; No reaction
predicted with P3; parent of Bapineuzumab
[11–13]
266 Raised against synthetic Aβ; epitope lies within aa 13–28;
recognises soluble monomer and multiple
C-terminal variations
Cross reacts with various plasma proteins containing the
core sequence KLVFF; does not cross react with P3;
parent of Solanezumab
[11–14]
Hunter and Brayne Journal of Negative Results in BioMedicine  (2017) 16:8 Page 2 of 2


Erratum to: Do anti-amyloid beta protein antibody cross reactivities confound Alzheimer disease research?

Reasons for and reasons against

A. Maciejowska

A. Godziek

M. Sajewicz

T. Kowalska

Turbidity patterns of spontaneous peptidization in an aqueous abiotic system and possible secondary peptide structures

Polymer integrated waveguide optical biosensor by using spectral splitting effect

Enzymatic Degradation of Pretreated Pig Bristles with Crude Keratinase of  PCM 2849

Incidence and admission rates for severe malaria and their impact on mortality in Africa

CASE REPORT Open Access
A case of diffuse cavernous hemangioma
of the appendix: laparoscopic surgery can
facilitate diagnosis and treatment
Chisato Takagi*, Kazuo Yamafuji, Hidena Takahashi, Atsunori Asami, Kaoru Takeshima, Hideo Baba,
Nobuhiko Okamoto and Kiyoshi Kubochi
Abstract
Background: A cavenous hemangioma of the appendix (CHA) is rare. The clinical pathophysiology and adequate
management of a CHA have not been sufficiently explained since reports on CHA are scarce.
Case presentation: A 56-year-old woman presented with chronic right lower quadrant pain. Abdominal contrast-
enhanced computed tomography revealed a thickened appendix (1.5 cm in diameter) and some focal calcifications
in the appendiceal wall. No acute inflammatory signs were visible around the appendix. For diagnosis and
treatment, we performed a laparoscopic surgery. Intraoperative findings included purple granular lesions that were
spread diffusely along the surface of the appendix. Since these lesions were spread to the terminal ileum,
laparoscopic ileocecal resection was performed. Upon macroscopic inspection, purple-colored, raspberry-like lesions
were found diffusely on the serosal surface of the appendix. No lesions were found on the mucosal surface.
Hematoxylin and eosin staining indicated the presence of blood-filled sinus-like spaces largely in the subserosal
layer. Immunohistochemistry analysis indicated that CD34-positive cells lined these spaces. Given these findings, we
diagnosed the patient with a diffuse cavernous vascular malformation of the appendix.
Conclusions: CHA is difficult to diagnose. A laparoscopic approach may be useful for both the diagnosis and
treatment of the disease.
Keywords: Vascular malformation, Cavernous hemangioma, Chronic abdominal pain, Appendicitis, Laparoscopic surgery
Background
Hemangiomas of the gastrointestinal tract are infrequently
encountered. They are also referred to as vascular malfor-
mations since their pathology consists of a collection of
malformed blood vessels [1]. Although most cases are
asymptomatic, they can present with overt or occult
bleeding in small and large intestinal lesions [2, 3].
Cavernous hemangioma of the appendix (CHA) is rare,
and reports of CHA are limited and have been written in
English, Russian, Japanese, German, and French [3–7].
Thus, their clinical pathophysiology and adequate man-
agement have not been explained sufficiently and are not
readily available to an international audience.
In this article, we report a case of diffuse CHA, which
was resected using a laparoscopic ileocecal procedure.
Case presentation
A 56-year-old woman presented to our hospital with right
lower quadrant pain. She experienced pain once every few
months beginning a few years previously. Her abdomen
was soft, with no peritoneal irritation signs or palpable
masses. An abdominal contrast-enhanced computed
tomography (CT) revealed a thickened appendix (1.5 cm in
diameter) and some focal calcifications in the appendiceal
wall. Abnormal findings were not seen in the terminal
ileum. There was no evidence of tumor and no acute
inflammatory signs (Fig. 1). Colonoscopy showed no
mucosal lesions in the appendiceal orifice and cecum.
Owing to the lack of findings requiring emergency treat-
ment, we followed her without therapy for 2 months. After
* Correspondence: ctakagi@a7.keio.jp
Department of Surgery, Saitama City Hospital, 2460 Mimuro, Midori-ku,
Saitama City, Saitama 336-8522, Japan
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made.
Takagi et al. Surgical Case Reports  (2017) 3:5 
DOI 10.1186/s40792-016-0276-9
2 months, we performed an abdominal contrast-enhanced
CT again because her abdominal pain did not alleviate. The
findings in the appendix were the same as those obtained
earlier. We then assumed that the patient had chronic
appendicitis and performed a laparoscopic surgery to
diagnose and treat the condition.
Intraoperative findings included purple-colored, granu-
lar lesions that were raspberry-like in appearance and
were spread diffusely along the surface of the appendix
(Fig. 2a). These lesions spread to the terminal ileum
(Fig. 2b, c). Therefore, laparoscopic ileocecal resection was
performed to completely resect the lesion. The resected
ileocecum contained approximately 6 cm of the ileum
(Fig. 2d). She was discharged with an uneventful postoper-
ative course. After surgery, her abdominal pain alleviated.
Macroscopic inspection of the resected specimen re-
vealed purple-colored, raspberry-like lesions, which were
spread diffusely on the serosal surface of the appendix. No
lesions were found on the mucosal surface (Fig. 3a).
Histological examination indicated that there were large
and small sinus-like spaces, largely in the subserosal layer.
The same finding was also observed in the submucosal and
proper muscular layer (Fig. 3b). Some of these spaces were
filled with blood (Fig. 3c). Cells that lined the vascular
spaces were strongly immunoreactive for CD34, which is
one of the main markers of endothelial cells (Fig. 3d). These
sinus-like spaces were thought to be malformed vessels.
Although there was chronic inflammation in the mucosal
layer of the appendix, the structure of the mucosal layer
was not injured. Finally, we diagnosed the patient with
diffuse cavernous vascular malformation of the appendix.
Fig. 1 Contrast-enhanced abdominal computed tomography (CT). A
thickened appendix, without signs of inflammation, including fat
stranding and extra-luminal fluid, was observed in the coronal plane
(yellow arrow). There were focal calcifications in the appendiceal wall
(yellow arrowheads)
Fig. 2 Intraoperative findings and outer image of the resected ileocecum. a Purple-colored nodular or granular lesions were presented with a raspberry-like
appearance that spread diffusely along the serosal surface of the appendix. b The lesion-like appendix spread to the terminal ileum. c The ileocecum was
mobilized and elevated outside the body before resection. The entire lesion is observed. d The resected ileocecum contains the entire lesion
Takagi et al. Surgical Case Reports  (2017) 3:5 Page 2 of 4
Discussion
As shown in this case, unexplained chronic right lower
quadrant pain and appendiceal wall thickening with focal
calcification, as evidenced by CT, may possibly be a case of
CHA, which is otherwise difficult to diagnose preopera-
tively. Owing to limited available reports, clinical manifesta-
tions and findings of various diagnostic images of CHA are
not well-known. Previously, CHA was reported to cause no
symptoms. For this reason, it was only incidentally discov-
ered during a surgery to treat other lesions [3, 5]. Another
report indicated that intraperitoneal bleeding was caused
by rupture of the CHA, which was also not diagnosed
preoperatively [6]. Another case was reported along with
acute appendicitis, which was diagnosed preoperatively [7].
Previous reports involving diagnostic imaging demon-
strated that CT, magnetic resonance imaging (MRI), and
colonoscopy were unable to detect the lesion [5]. Mean-
while, in other reports, no diagnostic imaging modalities
were employed and CHA was not diagnosed preoperatively
[3, 6]. Gastrointestinal cavernous hemangiomas can cause
pain and gastrointestinal bleeding [8, 9]. Furthermore, CT
imaging can detect focal calcification in gastrointestinal
hemangioma as a degenerative change [10]. Gastrointes-
tinal endoscopy, including esophagogastroduodenoscopy,
colonoscopy, and capsule endoscopy, can also be useful
diagnostic tools for gastrointestinal cavernous hemangioma
[8]. While the chronic right lower quadrant pain and the
appendiceal wall thickening with focal calcifications that
were observed by CT in this study have not been described
for CHA previously, they corroborate the pathology of
CHA. It is possible that obstruction of the appendiceal
lumen and congestion of the intestinal fluid in the appendix
can cause abdominal pain. Since a colonoscopy can reveal
only the appendiceal orifice, this examination might not
fully contribute to a diagnosis of CHA. However, a colonos-
copy may also be necessary to rule out other possible
diseases such as cancer or inflammatory diseases.
This case also demonstrates that laparoscopic surgery can
be a useful tool for both diagnosis and treatment. Diagnostic
laparoscopy for suspected appendicitis has been shown to
be useful for its diagnosis and treatment because it is usually
a simple and safe procedure that is helpful in obtaining
other diagnoses [11]. CHA has specific findings, such as a
purple-colored nodular or granular lesion that is raspberry-
like in appearance, which can be seen only during surgery
[3, 5]. In the present case, the same finding was observed
and laparoscopic resection was performed. A conservative
surgical resection, such as laparoscopic surgery, was thought
to be a sufficient treatment in order to relieve symptoms or
prevent complications caused by CHA. To the best of our
knowledge, this is the first report wherein CHA was
observed and resected using a laparoscopic approach.
Fig. 3 Macroscopic appearance and histological examination of the resected specimen. a No lesions were found on the mucosal surface. b There
were sinus-like spaces in the submucosal, proper muscular, and subserosal layers of the appendix, as indicated by hematoxylin and eosin staining.
c Some of these spaces were filled with blood. d CD34-positive cells were lined with vascular spaces on immunohistochemistry analysis
Takagi et al. Surgical Case Reports  (2017) 3:5 Page 3 of 4
Similarly, cavernous vascular malformation of the
mesoappendix has been reported [9, 12, 13]. Like CHA,
cavernous vascular malformation of the mesoappendix is a
rare disease and can form a tumor that results in abdominal
pain. CT and MRI can provide informative findings for
diagnosis. The relationship between appendiceal cavernous
hemangioma and mesoappendicial cavernous hemangioma
are not well known. To better understand the pathophysi-
ology, further clinical data are required.
Conclusions
CHA is a rare disease that is difficult to diagnose by his-
tory taking, physical examinations, and various diagnostic
imaging modalities because of its rarity. However, unex-
plained chronic right lower quadrant pain and appendiceal
wall thickening with focal calcification, as indicated by CT
imaging, may provide a basis for suspecting a diagnosis of
CHA. A laparoscopic approach may be useful for both the
diagnosis and treatment of CHA.
Abbreviations
CHA: Cavenous hemangioma of the appendix; CT: Computed tomography;
MRI: Magnetic resonance imaging
Acknowledgements
None.
Funding
No funding was received in support of this work.
Availability of data and materials
The dataset(s) supporting the conclusions of this article is(are) included
within the article (and its additional file(s)).
Authors’ contributions
CT described and designed the article. KY supervised the writing of the
manuscript. Other remaining co-authors collected the data and discussed the
content of the manuscript. All authors read and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Consent for publication
Written informed consent was obtained from the patient for publication of
this case report and any accompanying images.
Received: 21 September 2016 Accepted: 8 December 2016
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A case of diffuse cavernous hemangioma of the appendix: laparoscopic surgery can facilitate diagnosis and treatment

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