Do all the patients with vitamin B12 deficiency have pernicious anemia?

BACKGROUND: Vitamin B12 deficiency may result in pernicious anemia (PA). This study evaluated whether all the patients with vitamin B12 deficiency had PA. METHODS: The blood hemoglobin (Hb), iron, vitamin B12, folic acid, and homocysteine concentrations and mean corpuscular volume (MCV) in 90 vitamin B12-deficient patients were measured and compared with the corresponding data in 180 age- and sex-matched healthy control subjects. PA was defined by World Health Organization (WHO) as having an Hb concentration <13 g/dl for men and <12 g/dl for women, an MCV ≧ 100 fl, a serum vitamin B12 level <200 pg/ml, and serum gastric parietal cell antibody (GPCA) positivity. RESULTS: We found that 35 (38.9%) and 20 (22.2%) patients with vitamin B12 deficiency had deficiencies of Hb (men <13 g/dl, women <12 g/dl) and iron (<60 µg/dl), respectively. Moreover, 65 (72.2%) and 37 (41.1%) patients with vitamin B12 deficiency had abnormally high blood homocysteine level (>12.7 µM) and high MCV (≧100 fl), respectively. In addition, 43 (47.8%) vitamin B12-deficient patients with had GPCA positivity. Patients with vitamin B12 deficiency had a significantly higher frequency of Hb or iron deficiency, of abnormally elevated blood homocysteine level or high MCV, and of GPCA positivity than healthy control subjects (all P-values < 0.001). However, only 17 (18.9%) of 90 vitamin B12-deficient patients were diagnosed as having PA by the WHO definition. CONCLUSION: Only 18.9% of patients with vitamin B12 deficiency are discovered to have PA by the WHO definition.

Anemia and hematinic deficiencies in gastric parietal cell antibody-positive and antibody-negative erosive oral lichen planus patients with thyroid antibody positivity.

BACKGROUND/PURPOSE: Serum gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) are found in some erosive oral lichen planus (EOLP) patients. This study assessed whether serum GPCA, TGA and TMA and EOLP itself played significant roles in causing anemia and hematinic deficiencies in TGA/TMA-positive EOLP patients with GPCA positivity (GPCA+/TGA/TMA/EOLP patients) or negativity (GPCA-/TGA/TMA/EOLP patients). METHODS: The mean corpuscular volume (MCV) and mean blood hemoglobin (Hb), iron, vitamin B12, and folic acid levels were measured and compared between any two of the four groups of 29 GPCA+/TGA/TMA/EOLP patients, 80 GPCA-/TGA/TMA/EOLP patients, 198 all antibodies-negative EOLP patients (Abs-/EOLP patients), and 218 healthy control individuals. RESULTS: GPCA+/TGA/TMA/EOLP patients had significantly lower mean Hb and vitamin B12 levels as well as significantly greater frequencies of Hb, iron, and vitamin B12 deficiencies than healthy controls. GPCA+/TGA/TMA/EOLP patients had significantly lower serum vitamin B12 level and higher MCV as well as a significantly greater frequency of vitamin B12 deficiency than GPCA-/TGA/TMA/EOLP patients. Furthermore, both GPCA-/TGA/TMA/EOLP and Abs-/EOLP patients did have significantly lower mean Hb, MCV, and iron (for women only) levels, as well as significantly greater frequencies of Hb and iron deficiencies than healthy controls. However, there were no significant differences in measured blood data between GPCA-/TGA/TMA/EOLP and Abs-/EOLP patients. CONCLUSION: We conclude that serum GPCA is the major factor causing vitamin B12 deficiency, macrocytosis and pernicious anemia in GPCA+/TGA/TMA/EOLP patients. ELOP itself but not TGA/TMA positivity plays a significant role in causing anemia and hematinic deficiencies in GPCA-/TGA/TMA/EOLP patients.

Hepatocyte FRS2α is essential for the endocrine fibroblast growth factor to limit the amplitude of bile acid production induced by prandial activity.

In addition to being positively regulated by prandial activity, bile acid production is also negatively controlled by the endocrine fibroblast growth factor 19 (FGF19) or the mouse ortholog FGF15 from the ileum that represses hepatic cholesterol 7 α-hydroxylase (Cyp7a1) expression through activating FGF receptor four (FGFR4). However, how these two regulatory mechanisms interplay to control bile acid homeostasis in the body and the downstream pathways by which FGFR4 regulates Cyp7a1 expression are not fully understood. Here we report that hepatocyte FGFR substrate 2α (FRS2α), a scaffold protein essential for canonical FGFRs to activate the ERK and AKT pathways, was required for the regulation of bile acid production by the FGF15/19-FGFR4 signaling axis. This occurred through limiting the extent of increases in Cyp7a1 expression induced by prandial activity. Excess FGFR4 kinase activity reduced the amplitude of the increase whereas a lack of FGFR4 augmented the increase of Cyp7a1 expression in the liver. Ablation of Frs2α alleles in hepatocytes abrogated the regulation of Cyp7a1 expression by FGFR4. Together, the results demonstrate that FRS2α-mediated pathways are essential for the FGF15/FGF19-FGFR4 signaling axis to control bile acid homeostasis.