Title: Endoscopic and histopathological hints on infections in patients of common variable
immunodeficiency disorder with gastrointestinal symptoms
Version: 3 Date: 01 Sep 2023
Reviewer:  Timi Martelius
Reviewer's report:
The article deals  with an important subject of GI disease in CVID. There is scarcity of data in
the area and the pathogenesis and therapy is not well understood.   So this patient series is a
welcome addition to the existing data.
There are several typographical errors and some odd sentences.  I recommend checking the
English of the text and the spelling of words.
The data is well presented, but there are some concerns in the discussion and conclusions and
the limitations of the study.
Page 3 Row 15: Where does this 60% come from? Sounds overestimated, especially for such
severe findings as malabsorbtion.  E.g. Chapel gives 9% for enteropathy
Page 4 Row 14 I would leave "Whereas" out.
Page 4 Row 19  Why are these references after this quite obvious sentence?  Aren't they rather
referring to the previous sentence?
Page 6 row 4.  "A total of 87 CVID patients were hospitalized"  How many were followed in
the outpatient clinic?
Page 8 row 15.  These patients were quite severely affected with 89% with malabsorbtion.
This should be discussed in the discussion and compared with previous studies about CVID
enteropathy.  And also in the limitations section concerning the patient selection and biases.
Page 8 Row 21. I suppose this IgG level was at diagnosis, without immunoglobulin therapy?
This should be stated clearly.
Page 9 Row 8.  Were these GI infections present at the time of endoscopy or had they been
treated previously?
Page 10 Row 17.  This is a known feature of CVID, and that could be mentioned here.
Page 11 Row 13.  The almost total absence of colitis is surprising. Again compare with other
studies in the discussion.
Page 14 Row 5.  This sentence lacks a verb. Reformulate.
Page 14 Row 12-13.  The sentence starting with "However, it is hard.." is difficult to follow.
What do you mean?  Reformulate or remove.
Page 14 Row 19-20.  That NLH is caused by infection is still a theory although a
good one.  This should be emphasized in discussion.  Also the authors should mention
the lymphoproliferation present elsewhere in the body in CVID patients, such as GLILD,
splenomegaly and lymphadenopathy, where B-cell maturation defects are thought to play some
role.
Page 15 Row 4.   Chronic norovirus could be mentioned here.
Page 15 Row 15.  The percentage of your center's CVID patients that have had endoscopy is quite
low and consequently the clinical findings are quite severe (villus atrophy and malabsorbtion was
common).  This should be commented in  limitations and discussed in the discussion, comparing
findings with other endoscopy studies in CVID patients.
Page 16 Row 13.  This is controversial, since nodular lymphatic hyperplasia is very common
finding in CVID
Page 21 Table 1.  Are the infections in patients 4 and 5 really GI infections?
Title: Endoscopic and histopathological hints on infections in patients of common variable
immunodeficiency disorder with gastrointestinal symptoms
Version: 3 Date: 01 Sep 2023
Reviewer:  Timi Martelius
Reviewer's report:
The article deals  with an important subject of GI disease in CVID. There is scarcity of data in
the area and the pathogenesis and therapy is not well understood.   So this patient series is a
welcome addition to the existing data.
There are several typographical errors and some odd sentences.  I recommend checking the
English of the text and the spelling of words.
The data is well presented, but there are some concerns in the discussion and conclusions and
the limitations of the study.
Page 3 Row 15: Where does this 60% come from? Sounds overestimated, especially for such
severe findings as malabsorbtion.  E.g. Chapel gives 9% for enteropathy
Page 4 Row 14 I would leave "Whereas" out.
Page 4 Row 19  Why are these references after this quite obvious sentence?  Aren't they rather
referring to the previous sentence?
Page 6 row 4.  "A total of 87 CVID patients were hospitalized"  How many were followed in
the outpatient clinic?
Page 8 row 15.  These patients were quite severely affected with 89% with malabsorbtion.
This should be discussed in the discussion and compared with previous studies about CVID
enteropathy.  And also in the limitations section concerning the patient selection and biases.
Page 8 Row 21. I suppose this IgG level was at diagnosis, without immunoglobulin therapy?
This should be stated clearly.
Page 9 Row 8.  Were these GI infections present at the time of endoscopy or had they been
treated previously?
Page 10 Row 17.  This is a known feature of CVID, and that could be mentioned here.
Page 11 Row 13.  The almost total absence of colitis is surprising. Again compare with other
studies in the discussion.
Page 14 Row 5.  This sentence lacks a verb. Reformulate.
Page 14 Row 12-13.  The sentence starting with "However, it is hard.." is difficult to follow.
What do you mean?  Reformulate or remove.
Page 14 Row 19-20.  That NLH is caused by infection is still a theory although a
good one.  This should be emphasized in discussion.  Also the authors should mention
the lymphoproliferation present elsewhere in the body in CVID patients, such as GLILD,
splenomegaly and lymphadenopathy, where B-cell maturation defects are thought to play some
role.
Page 15 Row 4.   Chronic norovirus could be mentioned here.
Page 15 Row 15.  The percentage of your center's CVID patients that have had endoscopy is quite
low and consequently the clinical findings are quite severe (villus atrophy and malabsorbtion was
common).  This should be commented in  limitations and discussed in the discussion, comparing
findings with other endoscopy studies in CVID patients.
Page 16 Row 13.  This is controversial, since nodular lymphatic hyperplasia is very common
finding in CVID
Page 21 Table 1.  Are the infections in patients 4 and 5 really GI infections?
Please review this paper.
user
Title: Endoscopic and histopathological hints on infections in patients of common variable
immunodeficiency disorder with gastrointestinal symptoms
Version: 3 Date: 01 Sep 2023
Reviewer:  Timi Martelius
Reviewer's report:
The article deals  with an important subject of GI disease in CVID. There is scarcity of data in
the area and the pathogenesis and therapy is not well understood.   So this patient series is a
welcome addition to the existing data.
There are several typographical errors and some odd sentences.  I recommend checking the
English of the text and the spelling of words.
The data is well presented, but there are some concerns in the discussion and conclusions and
the limitations of the study.
Page 3 Row 15: Where does this 60% come from? Sounds overestimated, especially for such
severe findings as malabsorbtion.  E.g. Chapel gives 9% for enteropathy
Page 4 Row 14 I would leave "Whereas" out.
Page 4 Row 19  Why are these references after this quite obvious sentence?  Aren't they rather
referring to the previous sentence?
Page 6 row 4.  "A total of 87 CVID patients were hospitalized"  How many were followed in
the outpatient clinic?
Page 8 row 15.  These patients were quite severely affected with 89% with malabsorbtion.
This should be discussed in the discussion and compared with previous studies about CVID
enteropathy.  And also in the limitations section concerning the patient selection and biases.
Page 8 Row 21. I suppose this IgG level was at diagnosis, without immunoglobulin therapy?
This should be stated clearly.
Page 9 Row 8.  Were these GI infections present at the time of endoscopy or had they been
treated previously?
Page 10 Row 17.  This is a known feature of CVID, and that could be mentioned here.
Page 11 Row 13.  The almost total absence of colitis is surprising. Again compare with other
studies in the discussion.
Page 14 Row 5.  This sentence lacks a verb. Reformulate.
Page 14 Row 12-13.  The sentence starting with "However, it is hard.." is difficult to follow.
What do you mean?  Reformulate or remove.
Page 14 Row 19-20.  That NLH is caused by infection is still a theory although a
good one.  This should be emphasized in discussion.  Also the authors should mention
the lymphoproliferation present elsewhere in the body in CVID patients, such as GLILD,
splenomegaly and lymphadenopathy, where B-cell maturation defects are thought to play some
role.
Page 15 Row 4.   Chronic norovirus could be mentioned here.
Page 15 Row 15.  The percentage of your center's CVID patients that have had endoscopy is quite
low and consequently the clinical findings are quite severe (villus atrophy and malabsorbtion was
common).  This should be commented in  limitations and discussed in the discussion, comparing
findings with other endoscopy studies in CVID patients.
Page 16 Row 13.  This is controversial, since nodular lymphatic hyperplasia is very common
finding in CVID
Page 21 Table 1.  Are the infections in patients 4 and 5 really GI infections?
assistant