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A molecular genetic study has suggested that a common variant in the Fas gene promoter region prevents an autoimmune response to intracellular ribonucleoproteins in some patients with primary Sjögren’s syndrome. How this relates to pathogenesis is unclear, but testing polymorphisms against other autoantigens that relocate to the cell surface during apoptosis may be worth while.
The study in Australian patients tested whether genetic variants in this region were linked to the syndrome. Genotype distributions and allelic frequencies of the two common variants at positions −1377 and −670 were no different in patients and controls, but the allelic frequency of the −670 variant was significantly higher in patients without Ro/La autoantibodies than in those with, raising the possibility that this variant might somehow prevent immunological exposure to these intracellular antigens.
The study typed 101 patients with primary Sjögren’s syndrome and 108 ethnically matched controls for Fas gene promoter variants −1377G→A and −670A→G by PCR-SSP. Patients were grouped according to their autoantibody status to Ro/La ribonucleoproteins: Ro, La antibody negative; Ro positive only; Ro positive, precipitating La negative; and Ro positive, precipitating La positive.
Most patients with primary Sjögren’s syndrome have circulating autoantibodies to Ro/La ribonucleoproteins. Apoptosis may trigger the autoimmune response as these proteins migrate to the cell surface on blebs during the process. One theory is that abnormal apoptosis leads to the destruction of exocrine glands that is a feature of the syndrome, but the findings of this study indicate that this is not so—at least for these patients.