Clin Res Hepatol Gastroenterol. 2023 Aug;47(7):102154. doi: 10.1016/j.clinre.2023.102154.
최근 일본에서는 Guideline을 포함하여 다양한 cases Helicobacter pylori 관련 논문들이 나오고 있다면, 중국에서는 pathophysiology와 함께 retrospective 이긴 하지만 center 별로 clinical study 등 많은 논문들이 많이 발표되고 있습니다. 이런 추세에서 우리나라는 아직 관심이 부족해 보입니다 (관리자 생각 ^^'').
이번 연구는 AIG 환자에서 AIFA 동반 되었을 때 severe anemia, 특히 pernicious anemia로의 진행 가능성이 높기 때문에 AIG 환자에서 AIFA 여부 확인이 중요하다는 의미를 지닌 논문입니다. 살펴보도록 하겠습니다.
1. Introduction
AIG에서 관찰되는 anti-parietal cells antibodies (APCA), anti-intrinsic factors antibodies (AIFA)는 매우 중요한 autoantibodies 이며, fundic glands의 progressive atrophy는 pepsinogen I의 감소, achlorhydria, intrinsic factor의 감소를 가져와서 hypergastrinemia, entero-chromaffin like cell hyperplasia, pernicious anemia 등을 초래하게 됩니다. 전통적으로는 북유럽 혈통의 환자에서 주로 관찰되는 질환으로 알려져 있었지만, 최근 나오는 여러 연구를 바탕으로 살펴보면 거의 모든 민족과 인종에서 나타난다고 할 수 있습니다.
.. While traditionally viewed as a disease affecting predominantly patients of Northern European descent, growing studies suggested that it afflicts almost all racial and ethnic groups..
APCA는 높은 sensitivity를 보이고, AIFA는 높은 specificity를 보입니다. 이번 연구에서는 AIG 환자 중에서 AIFA를 가진 groups과 그렇지 않은 groups 사이에서 보이는 clinicopathological features를 살펴보고자 하였습니다.
2. Patients and methods
* Retrospective review of patients who underwent esophagogastroduodenoscopy (EGD) at the gastroenterology department
* Between January 2018 and August 2022
* AIG 진단기준: Endoscopically and/or histopathologically confirmed atrophy + APCA and/or AIFA
* Lab:
- Anemia: <11.9 g/dL (female) or 13.6 g/dL (male)
- Pernicious anemia: anemia, MCV > 100fL, vitamin B12 deficiency (<233pg/mL)
- Iron deficiency anemia: microcytic (MCV < 80 fL) anemia, serum ferritin level < 30 ng/mL
- H. pylori: Histologic evidence (H & E stain, anti-Hp immunohistochemical stain), Hp IgG antibody
- AIFA and APCA: indirect immunofluorescence technique
- Gastrin: Gastrin Radioimmunoassay Kit
3. Results
3.1. Clinical features
* Female-to-male ratio of 2:1
* Reduced PG Ⅰ levels : <90 ng/mL, Low PG Ⅰ/Ⅱ ratio: <9
* APCA(+), AIFA(+): 24 of 103 patients (23.30%)
* APCA(+), AIFA(-): 74 of 103 patients (71.84%)
* APCA(-), AIFA(+): 5 of 103 patients (4.85%)
Figure 1. Clinical features of 103 patients with AIG.
3.2. Comparative analysis based on the presence or absence of AIFA
* Mean age of AIG patients with AIFA was older than those without AIFA
* Patients with AIFA were more likely to have anemia than those without AIFA (not significantly, P=0.08)
* AIFA-positive patients had more severe anemia (Hb level: 83.19±19.76 g/L vs. 98.32±11.86 g/L, P=0.004) and higher MCVs (107.59± 22.61 fL vs. 77.72±10.97 fL, P<0.001)
* All the patients with PA were AIFA-positive
* AIFA-positive patients with anemia: Expressed PA/anemia (68.75%, 11/16), IDA/anemia (25.00%, 4/16)
* AIG patients with AIFA had lower serum vitamin B-12 levels
* PG, Gastrin: no statistically significant differences
Figure 2. Comparative analysis according to the presence or absence of AIFA.
3.3. Histopathological findings
Figure 3. Histopathological findings of AIG patients.
* Histopathological findings of the gastric corpus by type of AIFA test: no statistically significant differences
Figure 4. Histopathological findings of corpus by type of AIFA test.
3.4. Comorbid autoimmune disorders
* 34/103 (33.01%): concomitant autoimmune diseases
Figure 5. Comorbid autoimmune disorders of AIG patients.
* 46/103 (44.66%): Serum antibody screening results (positive)
Figure 6. Serum antibodies of AIG patients.
4. Discussion
* AIG is not exclusively associated with the elderly, as a small portion of the population was under 40 years of age (14.56%).
* Patients with anemia who tested positive for AIFA had lower hemoglobin levels compared to those who tested negative, indicating a more severe anemia in the former group.
* AIG patients with AIFA-positive have a higher risk of developing PA.
* All AIG patients with PA were AIFA-positive, but AIFA-positive patients could also have IDA.
* Vitamin B-12 supplementation is the fundamental treatment for AIG patients with PA. (Taking vitamin B-12 orally has equally effective as parenteral administration)
* This study had several limitations. Firstly, its retrospective and single-center design may limit the generalizability of the findings. Secondly, the rigorous diagnostic criteria used for identifying AIG patients may have missed some individuals in the early stages of the disease, and selection bias could not be entirely avoided. In order to provide a more thorough understanding of AIG’s clinical presentation and related risks, future research should include patients from multiple healthcare settings and large samples.
5. Conclusion
Our study provided detailed insights into the clinicopathological characteristics of AIG in Chinese patients. We found that AIG patients with AIFA are more likely to have severe anemia, particularly PA. Furthermore, the presence of AIFA was not associated with the histopathology of the gastric mucosa. Thus, when AIG patients test positive for AIFA, it is crucial to perform a laboratory workup for anemia, particularly for PA. We believe that these findings will facilitate the diagnosis and management of AIG.
우리나라에서도 AIG에 대한 임상적 연구가 나오길 기대해 봅니다.
Abstract
Background and Aim: Autoimmune gastritis (AIG) is a prominent risk factor for pernicious anemia (PA) and gastric neoplasia. This study aimed to investigate the clinicopathological characteristics of AIG patients in China, with a focus on those who had positive anti-intrinsic factor antibodies (AIFA).
Methods: A total of 103 AIG patients who were diagnosed between January 2018 and August 2022 were reviewed in a large academic tertiary teaching hospital. Patients were divided into two groups based on the presence or absence of AIFA, and their serologic and histopathological characteristics were analyzed.
Results: The mean age of the 103 AIG patients was 54.16±11.92 years (range 23-79), with 69 (66.99%) being women. AIFA were present in 28.16% of patients. Patients with AIFA-positive had a higher risk of PA than those with AIFA-negative, as demonstrated by a larger mean corpuscular volume (MCV), lower hemoglobin level, and lower vitamin B-12 level (P<0.05). There were no statistically significant differences in gastric histopathology, gastrin level, and pepsinogen level when patients were divided into AIFA-positive and AIFA-negative group. Of the 103 cases, 34 (33.01%) were concomitant with other autoimmune diseases, with autoimmune thyroid diseases being the most common (25.24%, 26/103). Thyroid peroxidase antibody, which accounted for 45.45% (25/55), was the most prevalent thyroid antibody, followed by anti-thyroglobulin antibody (34.55%, 19/55), thyroid stimulating antibody (12.73%, 7/55), and thyrotropin receptor antibody (3.64%, 2/55).
Conclusion: This study highlights the increased risk of severe anemia in AIFA-positive AIG patients, particularly for PA. Clinicians should consider the presence of AIFA as a warning sign for PA and prioritize early diagnosis and appropriate treatment to prevent serious complications.
Clin Res Hepatol Gastroenterol. 2023 Aug;47(7):102154. doi: 10.1016/j.clinre.2023.102154.
최근 일본에서는 Guideline을 포함하여 다양한 cases Helicobacter pylori 관련 논문들이 나오고 있다면, 중국에서는 pathophysiology와 함께 retrospective 이긴 하지만 center 별로 clinical study 등 많은 논문들이 많이 발표되고 있습니다. 이런 추세에서 우리나라는 아직 관심이 부족해 보입니다 (관리자 생각 ^^'').
이번 연구는 AIG 환자에서 AIFA 동반 되었을 때 severe anemia, 특히 pernicious anemia로의 진행 가능성이 높기 때문에 AIG 환자에서 AIFA 여부 확인이 중요하다는 의미를 지닌 논문입니다. 살펴보도록 하겠습니다.
1. Introduction
AIG에서 관찰되는 anti-parietal cells antibodies (APCA), anti-intrinsic factors antibodies (AIFA)는 매우 중요한 autoantibodies 이며, fundic glands의 progressive atrophy는 pepsinogen I의 감소, achlorhydria, intrinsic factor의 감소를 가져와서 hypergastrinemia, entero-chromaffin like cell hyperplasia, pernicious anemia 등을 초래하게 됩니다. 전통적으로는 북유럽 혈통의 환자에서 주로 관찰되는 질환으로 알려져 있었지만, 최근 나오는 여러 연구를 바탕으로 살펴보면 거의 모든 민족과 인종에서 나타난다고 할 수 있습니다.
.. While traditionally viewed as a disease affecting predominantly patients of Northern European descent, growing studies suggested that it afflicts almost all racial and ethnic groups..
APCA는 높은 sensitivity를 보이고, AIFA는 높은 specificity를 보입니다. 이번 연구에서는 AIG 환자 중에서 AIFA를 가진 groups과 그렇지 않은 groups 사이에서 보이는 clinicopathological features를 살펴보고자 하였습니다.
2. Patients and methods
* Retrospective review of patients who underwent esophagogastroduodenoscopy (EGD) at the gastroenterology department
* Between January 2018 and August 2022
* AIG 진단기준: Endoscopically and/or histopathologically confirmed atrophy + APCA and/or AIFA
* Lab:
- Anemia: <11.9 g/dL (female) or 13.6 g/dL (male)
- Pernicious anemia: anemia, MCV > 100fL, vitamin B12 deficiency (<233pg/mL)
- Iron deficiency anemia: microcytic (MCV < 80 fL) anemia, serum ferritin level < 30 ng/mL
- H. pylori: Histologic evidence (H & E stain, anti-Hp immunohistochemical stain), Hp IgG antibody
- AIFA and APCA: indirect immunofluorescence technique
- Gastrin: Gastrin Radioimmunoassay Kit
3. Results
3.1. Clinical features
* Female-to-male ratio of 2:1
* Reduced PG Ⅰ levels : <90 ng/mL, Low PG Ⅰ/Ⅱ ratio: <9
* APCA(+), AIFA(+): 24 of 103 patients (23.30%)
* APCA(+), AIFA(-): 74 of 103 patients (71.84%)
* APCA(-), AIFA(+): 5 of 103 patients (4.85%)
Figure 1. Clinical features of 103 patients with AIG.
3.2. Comparative analysis based on the presence or absence of AIFA
* Mean age of AIG patients with AIFA was older than those without AIFA
* Patients with AIFA were more likely to have anemia than those without AIFA (not significantly, P=0.08)
* AIFA-positive patients had more severe anemia (Hb level: 83.19±19.76 g/L vs. 98.32±11.86 g/L, P=0.004) and higher MCVs (107.59± 22.61 fL vs. 77.72±10.97 fL, P<0.001)
* All the patients with PA were AIFA-positive
* AIFA-positive patients with anemia: Expressed PA/anemia (68.75%, 11/16), IDA/anemia (25.00%, 4/16)
* AIG patients with AIFA had lower serum vitamin B-12 levels
* PG, Gastrin: no statistically significant differences
Figure 2. Comparative analysis according to the presence or absence of AIFA.
3.3. Histopathological findings
Figure 3. Histopathological findings of AIG patients.
* Histopathological findings of the gastric corpus by type of AIFA test: no statistically significant differences
Figure 4. Histopathological findings of corpus by type of AIFA test.
3.4. Comorbid autoimmune disorders
* 34/103 (33.01%): concomitant autoimmune diseases
Figure 5. Comorbid autoimmune disorders of AIG patients.
* 46/103 (44.66%): Serum antibody screening results (positive)
Figure 6. Serum antibodies of AIG patients.
4. Discussion
* AIG is not exclusively associated with the elderly, as a small portion of the population was under 40 years of age (14.56%).
* Patients with anemia who tested positive for AIFA had lower hemoglobin levels compared to those who tested negative, indicating a more severe anemia in the former group.
* AIG patients with AIFA-positive have a higher risk of developing PA.
* All AIG patients with PA were AIFA-positive, but AIFA-positive patients could also have IDA.
* Vitamin B-12 supplementation is the fundamental treatment for AIG patients with PA. (Taking vitamin B-12 orally has equally effective as parenteral administration)
* This study had several limitations. Firstly, its retrospective and single-center design may limit the generalizability of the findings. Secondly, the rigorous diagnostic criteria used for identifying AIG patients may have missed some individuals in the early stages of the disease, and selection bias could not be entirely avoided. In order to provide a more thorough understanding of AIG’s clinical presentation and related risks, future research should include patients from multiple healthcare settings and large samples.
5. Conclusion
Our study provided detailed insights into the clinicopathological characteristics of AIG in Chinese patients. We found that AIG patients with AIFA are more likely to have severe anemia, particularly PA. Furthermore, the presence of AIFA was not associated with the histopathology of the gastric mucosa. Thus, when AIG patients test positive for AIFA, it is crucial to perform a laboratory workup for anemia, particularly for PA. We believe that these findings will facilitate the diagnosis and management of AIG.
우리나라에서도 AIG에 대한 임상적 연구가 나오길 기대해 봅니다.
Abstract
Background and Aim: Autoimmune gastritis (AIG) is a prominent risk factor for pernicious anemia (PA) and gastric neoplasia. This study aimed to investigate the clinicopathological characteristics of AIG patients in China, with a focus on those who had positive anti-intrinsic factor antibodies (AIFA).
Methods: A total of 103 AIG patients who were diagnosed between January 2018 and August 2022 were reviewed in a large academic tertiary teaching hospital. Patients were divided into two groups based on the presence or absence of AIFA, and their serologic and histopathological characteristics were analyzed.
Results: The mean age of the 103 AIG patients was 54.16±11.92 years (range 23-79), with 69 (66.99%) being women. AIFA were present in 28.16% of patients. Patients with AIFA-positive had a higher risk of PA than those with AIFA-negative, as demonstrated by a larger mean corpuscular volume (MCV), lower hemoglobin level, and lower vitamin B-12 level (P<0.05). There were no statistically significant differences in gastric histopathology, gastrin level, and pepsinogen level when patients were divided into AIFA-positive and AIFA-negative group. Of the 103 cases, 34 (33.01%) were concomitant with other autoimmune diseases, with autoimmune thyroid diseases being the most common (25.24%, 26/103). Thyroid peroxidase antibody, which accounted for 45.45% (25/55), was the most prevalent thyroid antibody, followed by anti-thyroglobulin antibody (34.55%, 19/55), thyroid stimulating antibody (12.73%, 7/55), and thyrotropin receptor antibody (3.64%, 2/55).
Conclusion: This study highlights the increased risk of severe anemia in AIFA-positive AIG patients, particularly for PA. Clinicians should consider the presence of AIFA as a warning sign for PA and prioritize early diagnosis and appropriate treatment to prevent serious complications.