A famiy study of pernicious anaemia. I. Autoantibodies, achlorhydria, serum pepsinogen and vitamin B12.

Abstract

Summary Anaemia was not a common finding in a study of 386 relatives and 46 spouses of patients with pernicious anaemia. When present, it was more often hypochromic than macrocytic in nature and affected women more frequently than men.The serum levels of vitamin B12 decreased with age in first‐degree relatives and were significantly lower in relatives over the age of 70 than in control subjects matched for age and sex. The serum pepsinogen also decreased with age in first‐degree relatives with achlorhydria but increased with age in relatives who secreted acid and in control subjects. The difference between relatives with and without achlorhydria was significant. Achlorhydria, which became increasingly common with age in first‐degree relatives, preceded the fill in the serum pepsinogen.The prevalence of gastric parietal cell antibodies increased with age in both first‐degree relatives and matched control subjects. It was significantly higher in the former than in the latter but of the same order in second‐degree relatives and spouses as in control subjects. Antibody to intrinsic factor was rare in the relatives and not found in spouses or control subjects. Most of the relatives with the antibody had overt or latent pernicious anaemia. Antibodies to thyroid antigens were not significantly more common in first‐degree relatives than in control subjects.In the first‐degree relatives the gastric parietal cell antibody was associated with significant reductions in the serum levels of vitamin B12 and pepsinogen and with a significant increase in the prevalence of achlorhydria. The sequence of the changes was suggestive of the gradual onset and evolution of autoimmune gastritis in a proportion of the relatives.In view of the known familial coexistence of pernicious anaemia and iron‐deficiency anaemia, and in view of the association between the latter and gastric autoimmunity, a correlation was sought between hypochromia and parietal cell antibodies in the relatives. Although a positive correlation was found further analysis suggested that it was an effect of age and did not imply a causal relationship.