Association of severe rheumatoid arthritis with heterozygosity for alpha 1-antitrypsin deficiency

Clin Genet. 1980 Feb;17(2):153-60. doi: 10.1111/j.1399-0004.1980.tb00125.x.

Abstract

Genetic types of alpha 1-antitrypsin (protease inhibitor types, or Pi types) were determined in 108 patients with rheumatoid arthritis. These patients were selected for severely destructive disease and had classical rheumatoid arthritis according to ARA criteria, were seropositive, and had joint erosions shown by X-ray. Heterozygotes for the deficiency Z allele (Pi types MZ, SZ, etc.) were found among 9.2% of patients and 3.5% of a control adult population. The increased frequency in patients was statistically significant. Heterozygotes were most frequent among female patients with an early onset of disease. Heterozygosity for alpha 1-antitrypsin deficiency may be a factor in familial recurrence of rheumatoid arthritis. Among 98 patients with juvenile rheumatoid arthritis not selected for severity, 4.1% were Z heterozygotes compared with 1.3% of control children, not a statistically significant difference. Reduced concentrations of alpha 1-antitrypsin in Z heterozygotes may be inadequate to inhibit the proteolytic enzymes released into the joints of adults with rheumatoid arthritis during phagocytosis of immune complexes. This may be a factor promoting severe joint destruction.

MeSH terms

  • Adult
  • Arthritis, Juvenile / enzymology
  • Arthritis, Juvenile / genetics
  • Arthritis, Rheumatoid / enzymology
  • Arthritis, Rheumatoid / genetics*
  • Child
  • Child, Preschool
  • Female
  • Heterozygote*
  • Humans
  • Joints / metabolism
  • Male
  • Middle Aged
  • Peptide Hydrolases / metabolism
  • Risk
  • Sex Factors
  • alpha 1-Antitrypsin / genetics*
  • alpha 1-Antitrypsin Deficiency

Substances

  • alpha 1-Antitrypsin
  • Peptide Hydrolases