Intrinsic factor autoantibodies by luminescent immuno-precipitation system in patients with corpus atrophic gastritis

A 28-year-old Caucasian male with Hashimoto’s disease and vitiligo presented with two weeks of dizziness on exertion following pharyngitis which was treated with prednisone 40 mg by mouth once a day for five days. Initial workup revealed anemia, elevated lactate dehydrogenase (LDH), and low haptoglobin. He underwent workup for causes of hemolytic anemia which was remarkable for a peripheral blood smear with hypersegmented neutrophils and low vitamin B12 levels concerning for pernicious anemia. Parietal cell and intrinsic factor antibodies were negative, and he then underwent an esophagogastroduodenoscopy with biopsy. The biopsy was negative for Helicobacter pylori, and the immunohistochemical stains were suggestive of chronic atrophic gastritis. He was started on vitamin B12 1,000 mcg intramuscular injections daily. His hemoglobin, LDH, and haptoglobin normalized. Given the absence of the parietal cell antibody and intrinsic factor antibody, this is a rare case of seronegative pernicious anemia.

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Reassessment of Intrinsic Factor and Parietal Cell Autoantibodies in Atrophic Gastritis With Respect to Cobalamin Deficiency

The American Journal of Gastroenterology ◽

10.1038/ajg.2009.231 ◽

2009 ◽

Vol 104 (8) ◽

pp. 2071-2079 ◽

Cited By ~ 73

Author(s):

Edith Lahner ◽

Gary L Norman ◽

Carola Severi ◽

Susan Encabo ◽

Zakera Shums ◽

...

Keyword(s):

Atrophic Gastritis ◽

Parietal Cell ◽

Intrinsic Factor ◽

Cobalamin Deficiency ◽

Parietal Cell Autoantibodies

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The Hidden Face of Pernicious Anemia: Age-Related Progression of Autoimmune Gastritis from Iron Deficiency to Cobalamin Depletion.

Blood ◽

10.1182/blood.v106.11.3603.3603 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3603-3603

Author(s):

Chaim Hershko ◽

Aharon Ronson ◽

Moshe Souroujon ◽

Yzhak Maschler ◽

Judith Heyd ◽

...

Keyword(s):

Iron Deficiency ◽

Atrophic Gastritis ◽

Pernicious Anemia ◽

Serum Gastrin ◽

Screening Method ◽

Intrinsic Factor ◽

Autoimmune Gastritis ◽

Deficiency Anemia ◽

Age Cohorts ◽

H Pylori

Abstract Because gastric acid secretion is critical for food iron absorption, iron deficiency is a known complication of the achlorhydria associated with pernicious anemia at presentation or following cobalamin (Cbl) treatment. In a previous study employing high serum gastrin and strongly positive antiparietal cell antibodies as a screening method for autoimmune atrophic gastritis, we have found a very high (27%) prevalence of atrophic gastritis among young subjects with iron deficiency anemia (IDA). The objectives of the present study were to explore the degree of overlap between patients presenting with atrophic gastritis and microcytic (MVC<80 fl) IDA on one hand, and those presenting with Cbl deficiency and normocytic (MCV 80–100 fl) or macrocytic (MCV>100 fl) anemia typical of pernicious anemia. Of 160 patients diagnosed with autoimmune gastritis presenting with iron, Cbl, or combined deficiency over the years 2001–2005, 83 presented with microcytic IDA, 48 with normocytic and 29 with macrocytic indices. Serum Cbl was abnormal in 100% of macrocytic, 92% of normocytic and 46% of microcytic subjects. IDA patients were 21 y younger (41 ±15 vs 62±15 y), predominantly female (78 vs 41%) and with a higher proportion of active H pylori infection (42 vs 21%). However, there were also marked similarities between all subgroups including a high prevalence of thyroid disease (20%) and diabetes (8%) known for their association with the autoimmune polyendocrine syndrome, and the rate of anti-intrinsic factor positivity was the highest (42% vs 31%) among IDA patients. Stratification by age cohorts from <20 to >60 y showed a very regular correlation, with progressive increase in MCV from 68±9 to 119±8 fl, serum ferritin from 4±2 to 37±41 μg/L, hypergastrinemia from 349±247 to 800±627 u/mL (normal 61±17), and a progressive decrease of Cbl from 392±179 in the youngest, to 108±65 pg/mL in the oldest age cohort. The prevalence of H pylori infection was 87.5% at age <20 y, 47% at 20–40 y, 37.5 % at 41–60 y and 12.5% at age > 60y implying a spontaneous elimination of H pylori by achlorhydria of increasing severity and duration. H pylori eradication by triple therapy in 24 patients resulted in a decrease in serum gastrin from 476±391 to 218±220 u/mL (paired t-test=0.00086) within 19± 12 months and complete remission of pernicious anemia in 2 patients. These findings challenge the common notion that pernicious anemia is a disease of the elderly manifested in megaloblastic anemia, and imply a disease starting many years before the establishment of clinical Cbl deficiency through an autoimmune mechanism directed against gastric parietal cells, likely triggered by H pylori by means of antigenic mimicry. Because of the added strain of young age and fertility on iron requirements, IDA may precede Cbl deficiency by many years until the crucial loss of remaining intrinsic factor in a proportion of patients terminating in typical pernicious anemia.

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Family Study in Addisonian Pernicious Anemia

Blood ◽

10.1182/blood.v27.5.599.599 ◽

1966 ◽

Vol 27 (5) ◽

pp. 599-610 ◽

Cited By ~ 18

Author(s):

S. ARDEMAN ◽

I. CHANARIN ◽

A. JACOBS ◽

LORRAINE GRIFFITHS

Keyword(s):

Hydrochloric Acid ◽

Atrophic Gastritis ◽

Pernicious Anemia ◽

Parietal Cell ◽

Family Study ◽

Intrinsic Factor ◽

Gastric Biopsy ◽

Gastric Pathology ◽

Parietal Cell Antibodies ◽

Factor Secretion

Abstract Addisonian pernicious anemia was present in 6 of 9 siblings (Generation II). All 9 siblings had evidence of gastric pathology as judged by the presence of antibodies against parietal cells, abnormalities in the gastric biopsy, and diminution of secretion of acid and intrinsic factor. Parietal cell antibodies were present in 10 of 17 offspring of these 9 siblings who were available for study. Gastric biopsy in the older members of this generation (III) showed atrophic gastritis; some of the younger members showed superficial gastritis. Loss of intrinsic factor was always accompanied by loss of gastric secreting cells and there was no evidence that decline of intrinsic factor secretion occurred independently of hydrochloric acid.

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Chronic Atrophic Gastritis Presenting as Hemolytic Anemia due to Severe Vitamin B12 Deficiency

Case Reports in Hematology ◽

10.1155/2021/9571072 ◽

2021 ◽

Vol 2021 ◽

pp. 1-5

Author(s):

Amanda M. Woodford ◽

Rabhea Chaudhry ◽

Gabriella A. Conte ◽

Varsha Gupta ◽

Madhurima Anne

Keyword(s):

Vitamin B12 ◽

Atrophic Gastritis ◽

Hemolytic Anemia ◽

Neuropsychiatric Symptoms ◽

Intrinsic Factor ◽

Vitamin B12 Deficiency ◽

Disease Process ◽

Chronic Atrophic Gastritis ◽

Invasive Treatment ◽

B12 Deficiency

Vitamin B12 is an essential nutrient which plays an important role in neurological function, hematopoiesis, and DNA synthesis. Low levels usually stem from either poor intake or a malabsorptive process. Presently, the most common cause of vitamin B12 deficiency is food-bound cobalamin malabsorption, which occurs when there is impaired release of vitamin B12 from ingested food due to an outstanding factor preventing the release of the nutrient from its transport protein. Such causes include achlorhydria, gastritis, gastrectomy, or the use of PPIs or antacids. A rarer cause is autoimmune chronic atrophic gastritis, resulting in pernicious anemia. In this disease process, there is destruction of parietal cells and thus a reduction in intrinsic factor, which is essential to the absorption of vitamin B12. Deficiency will result in a variety of abnormalities including but not limited to pancytopenia, paresthesias, and neuropsychiatric symptoms. A rare manifestation of vitamin B12 deficiency is hemolytic anemia, which occurs due to intramedullary and extramedullary dysfunction. This case describes a 46-year-old male with no past medical history who presented with chest pain, fatigue, and progressive weakness, found to have hemolytic anemia, ultimately attributed to vitamin B12 deficiency. Antiparietal cell antibodies and intrinsic factor antibodies (IFA) were both negative. Still, the patient underwent an endoscopy with biopsies of the stomach; pathology was consistent with chronic metaplastic atrophic gastritis. The patient improved with intramuscular vitamin B12 supplementation. This case highlights both a rare cause and presentation of vitamin B12 deficiency. Patients with autoimmune chronic atrophic gastritis should have antiparietal cell or intrinsic factor antibodies. Still, seronegative patients have been reported, like this patient. Additionally, hemolytic anemia secondary to vitamin B12 deficiency is uncommon. The presentation will usually mirror that of a thrombotic microangiopathy (TMA), including hemolytic anemia with schistocytes on peripheral blood smear and thrombocytopenia, as it did in this patient. This clinical entity is described as pseudothrombotic microangiopathy and is crucial to identify in order to prevent the initiation of invasive treatment strategies such as plasmapheresis.

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A Case of Pernicious Anaemia with Psoriasis

Journal of Armed Forces Medical College Bangladesh ◽

10.3329/jafmc.v15i2.50850 ◽

2020 ◽

Vol 15 (2) ◽

pp. 243-245

Author(s):

Md Anisur Rahman ◽

Most Umme Habiba Begum ◽

Md Abdur Razzak ◽

Jesmin Khandker

Keyword(s):

Peripheral Neuropathy ◽

Vitamin B12 ◽

Atrophic Gastritis ◽

Intrinsic Factor ◽

Pernicious Anaemia ◽

Autoimmune Disorder ◽

Antibody Treatment ◽

Autoimmune Atrophic Gastritis ◽

Intrinsic Factor Antibody

Pernicious anaemia often poses diagnostic and therapeutic challenges to the clinician. Herein, we representing a 55 years old lady who presented with anaemia along with its classical symptoms and features of peripheral neuropathy due to Pernicious anaemia associated with Psoriasis and Arthropathy without any association of other autoimmune disorder. She had all objective evidences of autoimmune atrophic gastritis in gastric fundic biopsy and positive anti-intrinsic factor antibody. Treatment with injection vitamin B12 improved the condition rapidly. JAFMC Bangladesh. Vol 15, No 2 (December) 2019: 243-245

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Clinical Usefulness of the Serological Gastric Biopsy for the Diagnosis of Chronic Autoimmune Gastritis

Clinical and Developmental Immunology ◽

10.1155/2012/520970 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 25

Author(s):

Antonio Antico ◽

Marilina Tampoia ◽

Danilo Villalta ◽

Elio Tonutti ◽

Renato Tozzoli ◽

...

Keyword(s):

Atrophic Gastritis ◽

Intrinsic Factor ◽

Vitamin B12 Deficiency ◽

Chronic Atrophic Gastritis ◽

Autoimmune Gastritis ◽

Parietal Cell Antibodies ◽

B12 Deficiency ◽

Gastric Biopsies ◽

High Concentrations ◽

Highly Correlated

Aim. To assess the predictive value for chronic autoimmune gastritis (AIG) of the combined assay of anti-parietal-cell antibodies (PCA), anti-intrinsic-factor antibodies (IFA), anti-Helicobacter pylori(Hp) antibodies, and measurement of blood gastrin.Methods. We studied 181 consecutive patients with anemia, due to iron deficiency resistant to oral replacement therapy or to vitamin B12 deficiency.Results. 83 patients (45.8%) tested positive for PCA and underwent gastroscopy with multiple gastric biopsies. On the basis of the histological diagnosis, PCA-positive patients were divided into 4 groups: (1) 30 patients with chronic atrophic gastritis; they had high concentrations of PCA and gastrin and no detectable IFA; (2) 14 subjects with metaplastic gastric atrophy; they had high PCA, IFA, and gastrin; (3) 18 patients with nonspecific lymphocytic inflammation with increased PCA, normal gastrin levels, and absence of IFA; (4) 21 patients with multifocal atrophic gastritis with “borderline” PCA, normal gastrin, absence of IFA and presence of anti-Hp in 100% of the cases.Conclusions. The assay of four serological markers proved particularly effective in the diagnostic classification of gastritis and highly correlated with the histological profile. As such, this laboratory diagnostic profile may be considered an authentic “serological biopsy.”

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