Central nervous system mechanisms in Sjögren's syndrome.

he origin of the dry eye in Sjögren's syndrome has hardly been a subject of discussion as it is assumed that lymphoplasmocytic cell infiltration of the tear gland deteriorates its function to such a degree that it causes dry eye. Several observations, however, may not support the concept that tear gland degen-eration is the only causative factor in ocular dryness in Sjögren's syndrome. Sjögren's syndrome is thought to be the consequence of a generalised auto-immune induced exocrinopathy resulting in localised symptoms including dry eyes and mouth, and generalised symptoms including fatigue, myalgia, and arthralgia. 1 Rarely available epidemiological data suggest a prevalence varying between 1.5–4%, a phenomenon probably at least partly the result of the various classification criteria used. 2–4 Important components in the pathogenesis are the emergence 5 and persistence of auto-immune T cells 6 and a subsequent failure of apoptosis of these activated cells, 7 which might result in a persistent stimulation of B cells. Extensive lympho-plasmocytic infiltration of tear and sali-vary glands is thought to intervene with its secretory function, resulting in dry eyes and mouth. Even in idiopathic keratoconjunctivi-tis sicca, usually not thought to be based on generalised autoimmune disease, a local immune driven inflammatory reaction in the tear gland is also thought to interfere with the functional unit comprising the ocular surface, tear gland, and interconnecting reflex arc. 8 9 A critical decrease in androgen level leads to atrophy of the lacrimal glands. 10 Resulting apoptotic fragments of the intersti-tial and acinar cells might act as a source of potential autoantigens that subsequently might be presented either by interstitial antigen presenting cells or acinar cells to CD4 cell antigen receptors and start an immune response. 11 Several experimental and clinical observations cast doubt on the notion that tear gland degeneration is the only factor in deterioration of the tear flow in Sjögren's syndrome. Although in a murine model of Sjögren's syndrome, extensive lymphoplasmocytic cell infiltration of the lacrimal glands was observed, these glands contained a large number of apparently unaffected acinar and ductal cells. Despite this, lac-rimal function was impaired to such a degree that aqueous tear deficient kera-toconjunctivitis developed. 12 Immuno-histochemical analysis using specific antibodies to markers of parasympa-thetic, sympathetic, and sensory nerves demonstrated that the density and pattern of visceromotor and sensory inner-vation of the non-infiltrated parts of the lacrimal glands were indistinguishable from that of age matched healthy control lacrimal glands. Although …